Name (Synonyms) | Correlation | |
---|---|---|
drug1434 | UC-MSCs Wiki | 0.15 |
drug823 | Methylprednisolone Wiki | 0.12 |
drug1016 | Placebo Wiki | 0.12 |
drug760 | Lopinavir/ritonavir Wiki | 0.11 |
drug48 | Abidol hydrochloride Wiki | 0.11 |
drug1255 | SivoMixx (200 billion) Wiki | 0.11 |
drug802 | Mavrilimumab Wiki | 0.11 |
drug166 | Baricitinib Oral Tablet Wiki | 0.11 |
drug1685 | vv-ECMO only (no cytokine adsorption) Wiki | 0.11 |
drug1620 | oxygen therapy Wiki | 0.11 |
drug175 | Bevacizumab Injection Wiki | 0.11 |
drug423 | Dexamethasone injection Wiki | 0.11 |
drug1684 | vv-ECMO + cytokine adsorption (Cytosorb adsorber) Wiki | 0.11 |
drug952 | Oseltamivir Wiki | 0.10 |
drug591 | Hydroxychloroquine Wiki | 0.09 |
drug589 | Hydrocortisone Wiki | 0.09 |
drug1070 | Prednisone Wiki | 0.09 |
drug1567 | hydroxychloroquine Wiki | 0.09 |
drug1402 | Tocilizumab Wiki | 0.08 |
drug138 | Azithromycin with amoxicillin/clavulanate Wiki | 0.07 |
drug1277 | Standard administration of oxygen flow Wiki | 0.07 |
drug1164 | Ritonavir+Oseltamivir Wiki | 0.07 |
drug292 | Ceftriaxone Wiki | 0.07 |
drug1225 | Scanning Chest X-rays and performing AI algorithms on images Wiki | 0.07 |
drug130 | Azithromycin (Azithro) Wiki | 0.07 |
drug1497 | Xiyanping injection Wiki | 0.07 |
drug380 | Corticosteroid injection Wiki | 0.07 |
drug810 | Mefloquine Wiki | 0.07 |
drug1416 | Transfusion of SARS-CoV-2 Convalescent Plasma. Wiki | 0.07 |
drug972 | PROTECTIVE VENTILATION Wiki | 0.07 |
drug566 | Helmet Continuous Positive Airway Pressure (CPAP) Wiki | 0.07 |
drug1588 | mHealth Assessments Wiki | 0.07 |
drug39 | ASC09F+Oseltamivir Wiki | 0.07 |
drug215 | Breath test Wiki | 0.07 |
drug1645 | remdesivir Wiki | 0.07 |
drug1619 | oral nutrition supplement (ONS) enriched in eicosapentaenoic acid, gamma-linolenic acid and antioxidants Wiki | 0.07 |
drug411 | Defibrotide Injection Wiki | 0.07 |
drug1398 | Tinzaparin or unfractionated heparin Wiki | 0.07 |
drug854 | NA (no intervention) Wiki | 0.07 |
drug1622 | oxyhydrogen Wiki | 0.07 |
drug572 | Hidroxicloroquine Wiki | 0.07 |
drug859 | NK Cells Wiki | 0.07 |
drug957 | Oxygen Wiki | 0.07 |
drug65 | Allogenic pooled olfactory mucosa-derived mesenchymal stem cells Wiki | 0.07 |
drug768 | Low dose CT Wiki | 0.07 |
drug841 | Moxifloxacin or Levofloxacin Wiki | 0.07 |
drug1401 | Tociliuzumab Wiki | 0.07 |
drug1438 | UTTR1147A-matched Placebo Wiki | 0.07 |
drug229 | CAStem Wiki | 0.07 |
drug772 | Low-dose Chest CT Wiki | 0.07 |
drug811 | Mefloquine + azithromycin + / - tocilizumab Wiki | 0.07 |
drug1043 | Plaquenil 200Mg Tablet Wiki | 0.07 |
drug254 | COVID-19 Specific T Cell derived exosomes (CSTC-Exo) Wiki | 0.07 |
drug168 | Bedside lung ultrasound Wiki | 0.07 |
drug520 | Five-days oseltamivir Wiki | 0.07 |
drug1135 | Recombinant Human Interferon α2b Spray Wiki | 0.07 |
drug1453 | Usual Care Wiki | 0.07 |
drug1249 | Silymarin Wiki | 0.07 |
drug134 | Azithromycin 500Mg Oral Tablet Wiki | 0.07 |
drug786 | MSCs-derived exosomes Wiki | 0.07 |
drug945 | Oral Wiki | 0.07 |
drug1415 | Transfusion of COVID-19 convalescent plasma Wiki | 0.07 |
drug788 | MSTT1041A-matched Placebo Wiki | 0.07 |
drug1468 | Video based aerobic exercise Wiki | 0.07 |
drug599 | Hydroxychloroquine + placebo Wiki | 0.07 |
drug125 | Ayurveda Wiki | 0.07 |
drug1500 | Yinhu Qingwen Granula Wiki | 0.07 |
drug1349 | Taking biological samples Wiki | 0.07 |
drug119 | Automated oxygen administration - FreeO2 Wiki | 0.07 |
drug1405 | Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA] Wiki | 0.07 |
drug1198 | SCB-2019 with AS03 adjuvant Wiki | 0.07 |
drug1592 | mechanical ventilation Wiki | 0.07 |
drug1640 | quesionnair Wiki | 0.07 |
drug1199 | SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant Wiki | 0.07 |
drug1417 | Transfusion of standard Plasma. Wiki | 0.07 |
drug162 | Bacterial species isolated Wiki | 0.07 |
drug1580 | isocaloric/isonutrigenous ONS Wiki | 0.07 |
drug1376 | Thalidomide Wiki | 0.07 |
drug885 | Nicotinamide riboside Wiki | 0.07 |
drug345 | Combined use of a respiratory broad panel multiplex PCR and procalcitonin Wiki | 0.07 |
drug72 | Amoxicillin-clavulanate Wiki | 0.07 |
drug1641 | questionnair about Emerging Legal and Ehical Disputes Over Patient Confidentiality Wiki | 0.07 |
drug704 | Intravenous Immunoglobulin Wiki | 0.07 |
drug1309 | Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki | 0.07 |
drug664 | Immunoglobulin of cured patients Wiki | 0.07 |
drug161 | Bactek-R Wiki | 0.07 |
drug1014 | Piperacillin-tazobactam Wiki | 0.07 |
drug1311 | Sterile Water for Injection Wiki | 0.07 |
drug792 | Macrolide administered for 3-5 days Wiki | 0.07 |
drug663 | Imatinib tablets Wiki | 0.07 |
drug1152 | ResCure™ Wiki | 0.07 |
drug1047 | Plasma from COVID-19 convalescent patient Wiki | 0.07 |
drug962 | Ozone auto-hemotherapy Wiki | 0.07 |
drug47 | Abidol Hydrochloride combined with Interferon atomization Wiki | 0.07 |
drug1283 | Standard of Care (SoC) Wiki | 0.07 |
drug738 | Lenzilumab Wiki | 0.07 |
drug270 | CPAP Wiki | 0.07 |
drug793 | Macrolide administered for up to 14 days Wiki | 0.07 |
drug170 | Best Available Therapy Wiki | 0.07 |
drug367 | Convalescent SARS COVID-19 plasma Wiki | 0.07 |
drug1037 | Placebo solution Wiki | 0.07 |
drug1057 | Polysomnography Wiki | 0.07 |
drug1298 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation Wiki | 0.07 |
drug878 | NestaCell® Wiki | 0.07 |
drug528 | Fondaparinux Wiki | 0.07 |
drug1077 | Prone Wiki | 0.07 |
drug1015 | Piperacillin/tazobactam Wiki | 0.07 |
drug1247 | Shock-dependent hydrocortisone Wiki | 0.07 |
drug577 | High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma Wiki | 0.07 |
drug1499 | Yin Hu Qing Wen Granula(low does) Wiki | 0.07 |
drug318 | Ciclesonide Inhalation Aerosol Wiki | 0.07 |
drug1670 | systemic treatment Wiki | 0.07 |
drug309 | Chloroquine Diphosphate Wiki | 0.07 |
drug1399 | Tirofiban Injection Wiki | 0.07 |
drug752 | Lopinavir / ritonavir tablets combined with Xiyanping injection Wiki | 0.07 |
drug896 | Nitric Oxide delivered via LungFit™ system Wiki | 0.07 |
drug642 | Hyperbaric oxygen treatment (HBOT) i.e. inhalation of pressurized oxygen delivered by a hyperbaric chamber (drug/device) Wiki | 0.07 |
drug282 | Canakinumab 150 MG/ML [Ilaris] Wiki | 0.07 |
drug865 | NP-120 (Ifenprodil) Wiki | 0.07 |
drug1436 | UNIKINON (Chloroquine phosphate) 200mg tablets Wiki | 0.07 |
drug1026 | Placebo for Azithromycin Wiki | 0.07 |
drug1454 | Usual antibiotic treatment Wiki | 0.07 |
drug1048 | Plasma from a volunteer donor Wiki | 0.07 |
drug1563 | high-titer anti-Sars-CoV-2 plasma Wiki | 0.07 |
drug1051 | Plitidepsin 1.5 mg/day Wiki | 0.07 |
drug764 | Low Dose Radiation Therapy Wiki | 0.07 |
drug231 | CD55 Wiki | 0.07 |
drug999 | Pembrolizumab (MK-3475) Wiki | 0.07 |
drug1406 | Tocilizumab Injection Wiki | 0.07 |
drug1625 | patients receiving nasal high flow Wiki | 0.07 |
drug356 | Control arm Wiki | 0.07 |
drug1435 | ULTRAPROTECTIVE VENTILATION Wiki | 0.07 |
drug691 | Interferon-β1a Wiki | 0.07 |
drug373 | Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) and Traditional Chinese Medicines (TCMs) granules Wiki | 0.07 |
drug224 | Burnout Wiki | 0.07 |
drug1659 | standard medical treatment Wiki | 0.07 |
drug1027 | Placebo for Hydroxychloroquine Wiki | 0.07 |
drug976 | PTSD Wiki | 0.07 |
drug1052 | Plitidepsin 2.0 mg/day Wiki | 0.07 |
drug1553 | eculizumab Wiki | 0.07 |
drug1293 | Standard screening strategy Wiki | 0.07 |
drug769 | Low molecular weight heparin Wiki | 0.07 |
drug679 | Inhaled budesonide Wiki | 0.07 |
drug625 | Hydroxychloroquine and azithromycin treatment arm. Wiki | 0.07 |
drug291 | Ceftaroline Wiki | 0.07 |
drug1557 | favipiravir tablets+chloroquine phosphatetablets tablets Wiki | 0.07 |
drug1370 | Ten-days oseltamivir Wiki | 0.07 |
drug624 | Hydroxychloroquine and azithromycin treatment Wiki | 0.07 |
drug781 | MAS825 Wiki | 0.07 |
drug396 | DFV890 Wiki | 0.07 |
drug558 | HFNO Wiki | 0.07 |
drug165 | Baricitinib 4 MG Oral Tablet Wiki | 0.07 |
drug595 | Hydroxychloroquine + Placebo Wiki | 0.07 |
drug312 | Chloroquine diphosphate Wiki | 0.07 |
drug1545 | conventional management of patients Wiki | 0.07 |
drug1303 | Standard treatment according to the Clinical protocols Wiki | 0.07 |
drug800 | Matching placebo Wiki | 0.07 |
drug1517 | amoxicillin/clavulanate Wiki | 0.07 |
drug51 | Acetylsalicylic acid Wiki | 0.07 |
drug573 | High Flow Nasal Oxygen (HFNO) Wiki | 0.07 |
drug869 | Nafamostat Mesilate Wiki | 0.07 |
drug510 | Favipiravir + Standard of Care Wiki | 0.07 |
drug1299 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection Wiki | 0.07 |
drug1338 | T89 Wiki | 0.07 |
drug1564 | hormones Wiki | 0.07 |
drug1335 | Symptoms questionnare Wiki | 0.07 |
drug1682 | ventilatory support with oxygen therapy Wiki | 0.07 |
drug597 | Hydroxychloroquine + azithromycin + / - tocilizumab Wiki | 0.07 |
drug281 | Canakinumab Wiki | 0.07 |
drug784 | MSC Treatment Wiki | 0.07 |
drug1655 | severe covid-19 pneumonia with ET Wiki | 0.07 |
drug779 | Lung ultrasound Wiki | 0.07 |
drug753 | Lopinavir / ritonavir, alpha-interferon nebulization,Abidor Hydrochloride Wiki | 0.07 |
drug1666 | standardized Lung Ultrasound (LUS) examination Wiki | 0.07 |
drug66 | Almitrine Wiki | 0.07 |
drug174 | Bevacizumab Wiki | 0.07 |
drug204 | Blood sample and data record Wiki | 0.07 |
drug860 | NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells Wiki | 0.07 |
drug110 | Assessment of ventilator-associated pneumonia criteria Wiki | 0.07 |
drug237 | CM4620-Injectable Emulsion Wiki | 0.07 |
drug94 | Apple Watch Series 5 Wiki | 0.07 |
drug1630 | pirfenidone Wiki | 0.07 |
drug892 | Nitazoxanide Tablets Wiki | 0.07 |
drug959 | Oxygen-ozone therapy, probiotic supplementation and Standard of care Wiki | 0.07 |
drug1575 | iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System Wiki | 0.07 |
drug683 | Injective placebo Wiki | 0.07 |
drug1252 | Single fraction whole lung radiotherapy Wiki | 0.07 |
drug214 | Bone Marrow Harvest Wiki | 0.07 |
drug497 | Exposure (not intervention) - SARS-CoV-2 infection Wiki | 0.07 |
drug221 | Bromhexine Oral Tablet and/or hydroxychloroquine tablet Wiki | 0.07 |
drug598 | Hydroxychloroquine + lopinavir/ritonavir Wiki | 0.07 |
drug787 | MSTT1041A Wiki | 0.07 |
drug1093 | Pulmonary ultrasound Wiki | 0.07 |
drug1132 | Ravulizumab Wiki | 0.07 |
drug1688 | γ-Globulin Wiki | 0.07 |
drug103 | Aspirin 100mg Wiki | 0.07 |
drug813 | Melphalan Wiki | 0.07 |
drug90 | Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients Wiki | 0.07 |
drug1300 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation Wiki | 0.07 |
drug1019 | Placebo + Placebo Wiki | 0.07 |
drug1594 | mesenchymal stem cells Wiki | 0.07 |
drug817 | Meplazumab for Injection Wiki | 0.07 |
drug904 | No special intervention Wiki | 0.07 |
drug1546 | conventional oxygen Wiki | 0.07 |
drug147 | BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki | 0.07 |
drug491 | Exercise brochure Wiki | 0.07 |
drug543 | Glucose tablets Wiki | 0.07 |
drug1516 | alveolar recruitment Wiki | 0.07 |
drug271 | CT score Wiki | 0.07 |
drug762 | Lopinavir/ritonavir treatment Wiki | 0.07 |
drug494 | Experimental drug Wiki | 0.07 |
drug1090 | Pulmonary Physiotherapy Techniques Wiki | 0.07 |
drug1457 | VC Wiki | 0.07 |
drug1629 | photobiomodulation and photodynamic therapy Wiki | 0.07 |
drug948 | Oral placebo Wiki | 0.07 |
drug1532 | captopril 25mg Wiki | 0.07 |
drug372 | Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) Wiki | 0.07 |
drug276 | CYNK-001 Wiki | 0.07 |
drug522 | Fixed-duration higher dose Hydrocortisone Wiki | 0.07 |
drug521 | Fixed-duration Hydrocortisone Wiki | 0.07 |
drug1440 | Ultra-Low-dose radiotherapy Wiki | 0.07 |
drug1208 | Saline Control Wiki | 0.07 |
drug172 | Best Supportive Care Wiki | 0.07 |
drug1437 | UTTR1147A Wiki | 0.07 |
drug1053 | Plitidepsin 2.5 mg/day Wiki | 0.07 |
drug456 | Echo-Doppler Wiki | 0.07 |
drug556 | HCQ+AZT Wiki | 0.07 |
drug400 | Darunavir and Cobicistat Wiki | 0.07 |
drug220 | Bromhexine Hydrochloride Tablets Wiki | 0.07 |
drug1197 | SCB-2019 Wiki | 0.07 |
drug118 | Autologous Adipose MSC's Wiki | 0.07 |
drug96 | Arbidol Hydrochloride Granules Wiki | 0.07 |
drug881 | New screening strategy Wiki | 0.07 |
drug1672 | thalidomide Wiki | 0.07 |
drug1568 | hydroxychloroquine + azithromycin Wiki | 0.07 |
drug513 | Favipiravir tablets Wiki | 0.07 |
drug369 | Convalescent anti-SARS-CoV-2 plasma Wiki | 0.07 |
drug730 | LB1148 Wiki | 0.07 |
drug1593 | meplazumab for injection Wiki | 0.07 |
drug1301 | Standard therapy recommended by the Ministry of Health of the Russian Federation. Wiki | 0.07 |
drug1242 | Serology for Covid-19 Wiki | 0.07 |
drug1383 | Therapy Intervention Wiki | 0.07 |
drug415 | Dental pulp mesenchymal stem cells Wiki | 0.07 |
drug900 | No intervention Wiki | 0.07 |
drug1631 | placebo Wiki | 0.07 |
drug129 | Azithromycin Wiki | 0.07 |
drug163 | Baricitinib Wiki | 0.07 |
drug1220 | Sarilumab Wiki | 0.06 |
drug1042 | Placebos Wiki | 0.06 |
drug995 | Peginterferon Lambda-1A Wiki | 0.05 |
drug1160 | Rifampin Wiki | 0.05 |
drug1327 | Survey Wiki | 0.05 |
drug897 | Nivolumab Wiki | 0.05 |
drug603 | Hydroxychloroquine 200 Mg Oral Tablet Wiki | 0.05 |
drug136 | Azithromycin Tablets Wiki | 0.05 |
drug551 | HCQ Wiki | 0.05 |
drug824 | Methylprednisolone Sodium Succinate Wiki | 0.05 |
drug1137 | Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki | 0.05 |
drug269 | COViage Wiki | 0.05 |
drug785 | MSCs Wiki | 0.05 |
drug596 | Hydroxychloroquine + azithromycin Wiki | 0.05 |
drug899 | No Intervention Wiki | 0.05 |
drug550 | HB-adMSCs Wiki | 0.05 |
drug1403 | Tocilizumab (TCZ) Wiki | 0.05 |
drug1248 | Siltuximab Wiki | 0.05 |
drug1658 | standard care Wiki | 0.05 |
drug585 | Human immunoglobulin Wiki | 0.05 |
drug594 | Hydroxychloroquine + Azithromycin Wiki | 0.05 |
drug95 | Arbidol Wiki | 0.05 |
drug1523 | basic treatment Wiki | 0.05 |
drug253 | COVID-19 Serology Wiki | 0.05 |
drug938 | Online Survey Wiki | 0.05 |
drug1004 | Phase 1 Wiki | 0.05 |
drug568 | Heparin Wiki | 0.05 |
drug331 | Clopidogrel Wiki | 0.05 |
drug1280 | Standard of Care Wiki | 0.04 |
drug357 | Control group Wiki | 0.04 |
drug1184 | SARS-CoV-2 convalescent plasma Wiki | 0.04 |
drug893 | Nitric Oxide Wiki | 0.04 |
drug820 | Mesenchymal Stromal Cells Wiki | 0.04 |
drug592 | Hydroxychloroquine (HCQ) Wiki | 0.04 |
drug1005 | Phase 2 Wiki | 0.04 |
drug1044 | Plasma Wiki | 0.04 |
drug1060 | Povidone-Iodine Wiki | 0.04 |
drug252 | COVID-19 RT-PCR Wiki | 0.04 |
drug1542 | convalescent plasma Wiki | 0.04 |
drug247 | COVID-19 Convalescent Plasma Wiki | 0.04 |
drug1365 | Telerehabilitation Wiki | 0.04 |
drug1278 | Standard care Wiki | 0.03 |
drug335 | Colchicine Wiki | 0.03 |
drug1475 | Vitamin C Wiki | 0.03 |
drug73 | Anakinra Wiki | 0.03 |
drug608 | Hydroxychloroquine Sulfate Wiki | 0.02 |
drug1104 | Questionnaire Wiki | 0.02 |
drug360 | Convalescent Plasma Wiki | 0.02 |
drug1285 | Standard of care Wiki | 0.02 |
drug1035 | Placebo oral tablet Wiki | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
D011014 | Pneumonia NIH | 0.96 |
D011024 | Pneumonia, Viral NIH | 0.47 |
D018352 | Coronavirus Infections NIH | 0.19 |
D053717 | Pneumonia, Ventilator-Associated NIH | 0.18 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.18 |
D017563 | Lung Diseases, Interstitial NIH | 0.12 |
D011020 | Pneumonia, Pneumocystis NIH | 0.11 |
D016769 | Embolism and Thrombosis NIH | 0.09 |
D013577 | Syndrome NIH | 0.08 |
D008171 | Lung Diseases, NIH | 0.08 |
D030341 | Nidovirales Infections NIH | 0.07 |
D011251 | Pregnancy Complications, Infectious NIH | 0.07 |
D020181 | Sleep Apnea, Obstructive NIH | 0.07 |
D001049 | Apnea NIH | 0.07 |
D053120 | Respiratory Aspiration NIH | 0.07 |
D018410 | Pneumonia, Bacterial NIH | 0.07 |
D001261 | Pulmonary Atelectasis NIH | 0.07 |
D000077299 | Healthcare-Associated Pneumonia NIH | 0.07 |
D003967 | Diarrhea NIH | 0.07 |
D012891 | Sleep Apnea, NIH | 0.07 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.07 |
D012140 | Respiratory Tract Diseases NIH | 0.07 |
D007249 | Inflammation NIH | 0.07 |
D013313 | Stress Disorders, Post-Traumatic NIH | 0.07 |
D008173 | Lung Diseases, Obstructive NIH | 0.06 |
D007239 | Infection NIH | 0.06 |
D003141 | Communicable Diseases NIH | 0.06 |
D055371 | Acute Lung Injury NIH | 0.05 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.05 |
D012120 | Respiration Disorders NIH | 0.05 |
D012598 | Scoliosi NIH | 0.05 |
D007154 | Immune System Diseases NIH | 0.05 |
D004617 | Embolism NIH | 0.05 |
D009103 | Multiple Sclerosis NIH | 0.05 |
D055370 | Lung Injury NIH | 0.05 |
D012141 | Respiratory Tract Infections NIH | 0.05 |
D011248 | Pregnancy Complications NIH | 0.04 |
D009102 | Multiple Organ Failure NIH | 0.04 |
D013927 | Thrombosis NIH | 0.04 |
D003333 | Coronaviridae Infections NIH | 0.04 |
D012327 | RNA Virus Infections NIH | 0.04 |
D040921 | Stress Disorders, Traumatic NIH | 0.04 |
D011665 | Pulmonary Valve Insufficiency NIH | 0.03 |
D004417 | Dyspnea NIH | 0.03 |
D016638 | Critical Illness NIH | 0.03 |
D014777 | Virus Diseases NIH | 0.03 |
D007251 | Influenza, Human NIH | 0.03 |
D000860 | Hypoxia NIH | 0.02 |
D009369 | Neoplasms, NIH | 0.02 |
D002318 | Cardiovascular Diseases NIH | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0006515 | Interstitial pneumonitis HPO | 0.13 |
HP:0002088 | Abnormal lung morphology HPO | 0.09 |
HP:0002870 | Obstructive sleep apnea HPO | 0.07 |
HP:0002014 | Diarrhea HPO | 0.07 |
HP:0002104 | Apnea HPO | 0.07 |
HP:0100750 | Atelectasis HPO | 0.07 |
HP:0010535 | Sleep apnea HPO | 0.07 |
HP:0006536 | Obstructive lung disease HPO | 0.07 |
HP:0001907 | Thromboembolism HPO | 0.05 |
HP:0011947 | Respiratory tract infection HPO | 0.05 |
HP:0010444 | Pulmonary insufficiency HPO | 0.04 |
HP:0002098 | Respiratory distress HPO | 0.03 |
HP:0012418 | Hypoxemia HPO | 0.02 |
HP:0002664 | Neoplasm HPO | 0.02 |
HP:0001626 | Abnormality of the cardiovascular system HPO | 0.02 |
There are 180 clinical trials
Multiple sclerosis (MS) is an inflammatory, demyelinating disease which affects the central nervous system (CNS). The etiology of MS is unknown, although the immune system appears to play a role. Many different infectious agents have been proposed as potential causes for MS, including Epstein-Barr virus, human herpesvirus 6, and coronaviruses. Recently Dr. Sriram at Vanderbilt University has found evidence for active Chlamydia pneumonia infection in the CNS of MS patients. These findings have been replicated in part by other laboratories. The purpose of the current study is to test whether antibiotic treatment aimed at eradicating Chlamydia infection will reduce the disease activity in MS. The primary outcome measure will be reduction in new enhancing MS lesions on brain MRI. Forty patients will be entered into the trial. To be eligible, patients must have evidence of chlamydia infection in their spinal fluid and enhancing lesions on their pre-randomization MRI scans. Patients who meet these criteria will be randomized to either placebo or antibiotic therapy, and followed for 6 months on treatment.
The purpose of the study is to determine if the clinical course of pneumonia is more severe when both, bacterial and viral pathogens are find as possible causative agent and how does it affect treatment.
Diagnosis of pneumonia in the elderly is difficult because of the poor sensitivity and specificity of clinical signs as well as images from chest radiography (RT). New diagnostic tools such as thoracic low-dose computed tomography (CT), which exposes the patient to a weak dose of irradiation, could improve diagnosis. Moreover, low-dose CT could provide additional accuracy in the etiological clarification of pneumonia in elderly people. As a first step, the investigators aim to perform a 1 year (12 months of inclusion + 3 months of follow-up) prospective study including the Divisions of Internal Medicine, Rehabilitation, Geriatrics and Radiology of the University Hospitals of Geneva. In this study, patients >65 years old with a clinical suspicion of low respiratory tract infection (LRTI) will be included. They will be prescribed antimicrobial therapy. Both chest radiography and low-dose thoracic CT will be performed within the first 72 hours after admission, as will blood tests and a nasopharyngeal swab. The clinician's diagnosis, both before and after the results of the CT, will be compared at the end of the study to the adjudication committee's diagnostic opinion which will have access to all available clinical, laboratory and chest X-ray data and which will be considered the gold standard. At the end of the study, all the CT images will be blind-reviewed by two experts in radiology. The impact of CT scanning in the diagnosis of pneumonia will be assessed, both for its sensitivity and specificity in this population. During the first 12 months of the study, all patients will undergo a systematic nasopharyngeal swab at admission and at discharge, from which eluates will be conserved. During the next 12 months, virological and bacteriological polymerase chain reactions (PCR) will be performed, using new diagnostic tools, in order to determine the etiological diagnosis in this population and to evaluate the impact of the new tools in the management of pneumonia for this population. Analysis of these data will allow clinical, radiological and microbiological correlation.
Mortality of severe Community-Acquired Pneumonia (CAP) has not declined over time and is between 25 and 30% in sub-groups of patients. Corticosteroids (CTx) could down-regulate pulmonary and systemic inflammation, accelerate clinical resolution and decrease the rate of inflammation-associated systemic complications. Two recent meta-analyses suggest a positive effect on severe CAP day 28 survival when CTx are added to standard therapy. However they are based on only four trials gathering less than 300 patients, of which only one was positive. Recently published guidelines do not recommend CTx as part of CAP treatment. Therefore a well-powered trial appears necessary to test the hypothesis that CTx - and more specifically hydrocortisone - could improve day 28 survival of critically-ill patients with severe CAP, severity being assessed either on a Pulmonary Severity Index ≥ 130 (Fine class V) or by the use of mechanical ventilation or high-FiO2 high-flow oxygen therapy. A phase-III multicenter add-on randomized controlled double-blind superiority trial assessing the efficacy of hydrocortisone vs. placebo on Day 28 all-causes mortality, in addition to antibiotics and supportive care, including the correction of hypoxemia. Randomization will be stratified on: (i) centers; (ii) use of mechanical ventilation at the time of inclusion.
Description: For the sub-group of patients included with COVID19, failure is defined as death or need of respiratory support (mechanical ventilation or high-flow oxygen therapy);
Measure: Day 21 failure Time: at day 21Description: Sub-group of patients included with COVID19
Measure: P/F ratio measured daily from Day1 to Day7, at Day 14 and at Day 21 and/or at the end of ICU-stay Time: from day 1 to day 7, at day 14 and day 21 and/or at the end of ICU-stayDescription: Sub-group of patients included with COVID19
Measure: Proportion of patients needing endotracheal intubation Time: at day 21Description: Sub-group of patients included with COVID19
Measure: Proportion of patients experiencing secondary infection during their ICU-stay Time: From baseline to day 21REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia. The purpose of this study is to evaluate the effect of a range of interventions to improve outcome ofon patients admitted to intensive care with community-acquired pneumonia. In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple treatment modalities in the event of a respiratory pandemic resulting in critical illness. REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19.
Description: Primary end-point for patients with suspected or proven COVID-19 pandemic infection
Measure: Days alive and outside of ICU Time: Day 21Description: EQ5D-5L and WHODAS 2.0 (not completed in all regions)
Measure: Health-related Quality of life assessment Time: 6 monthsDescription: Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital
Measure: Destination at time of hospital discharge Time: Free text Day 90Description: Antibiotic Domain specific outcome
Measure: Occurrence of multi-resistant organism colonisation/infection Time: Day 90, censored at hospital dischargeDescription: Antibiotic Domain specific outcome
Measure: Occurrence clostridium difficile Time: Day 90, censored at hospital dischargeDescription: Macrolide Duration domain specific outcome, and COVID-19 Antiviral Domain specific outcome.
Measure: Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death Time: Day 90, censored at hospital dischargeDescription: Antiviral Domain specific outcome. Only required at selected sites.
Measure: Change from baseline influenza virus levels in upper and lower respiratory tract specimens Time: Day 3, up to Day 7Description: COVID-19 Antiviral Domain and COVID-19 Immune Modulation Domain specific endpoint
Measure: Serial detection of SARS-CoV-2 in upper or lower respiratory tract specimens (using only specimens collected for routine clinical testing) Time: Day 90, censored at hospital dischargeThe overall aim of the TREND study is to improve the differential diagnosis of bacterial and viral etiology in children below 5 years of age with clinical community acquired pneumonia. Specific objectives: - To assess the diagnostic accuracy of MxA for viral CAP (sub-study I) - To study etiologies in children with CAP (sub-study II) - To evaluate sensitivity and specificity for MariPOC® Respi test versus PCR for detection of respiratory viruses (sub-study III) - To assess sensitivity and specificity for a novel RPA-based point-of-care test versus PCR for detection of respiratory viruses (sub-study IV) - To assess long-term complications in children with CAP (sub-study V The study takes place at Sachs' Children and Youth hospital in Stockholm.
Description: Clinically relevant difference in MxA-levels between cases with viral and bacterial clinical CAP
Measure: MxA - cases with viral and bacterial clinical CAP Time: 2021Description: Clinically relevant difference in MxA-levels between cases with viral clinical CAP and controls
Measure: Mxa viral clinical CAP and controls Time: 2021Description: Proportion of respiratory pathogens in cases and controls, using real time PCR
Measure: PCR - respiratory pathogens in cases and controls Time: 2020Description: Sensitivity and specificity for different respiratory viruses with MariPOC® Respi as compared to real-time PCR
Measure: Sensitivity and specificity - MariPOC Time: 2021Description: Sensitivity and specificity for different respiratory viruses with a novel PCR-based point-of-care test as compared to PCR
Measure: Sensitivity and specificity a novel PCR-based point-of-care test Time: 2021Description: Difference in asthma prevalence between cases and controls and difference in number of hospital-requiring respiratory infections between cases and controls after 3, 7 and 10 years
Measure: Difference asthma prevalence and number of hospital-requiring respiratory infections - cases and controls, Time: 2027Description: Clinically relevant difference in MxA-levels comparing cases with viral clinical CAP with cases with atypical and mixed viral-bacterial clinical CAP as well as with controls with and without presence of respiratory viruses by PCR
Measure: Specific assessment of MxA as a clinical biomarker Time: 2021Description: Clinically relevant differences in MxA-levels in cases with regard to specific respiratory agents
Measure: Specific assessment of MxA as a clinical biomarker Time: 2021Description: Sensitivity and specificity for MxA in identifying viral clinical CAP
Measure: Specific assessment of MxA as a clinical biomarker Time: 2021Description: Sensitivity and specificity for identifying viral and bacterial infection respectively for CRP, PCT and combination test of CRP, PCT and MxA
Measure: Specific assessment of MxA as a clinical biomarker Time: 2021Description: Difference in CRP and PCT between children with viral, bacterial, atypical bacterial and mixed viral-bacterial infection
Measure: Assessment of PCT and CRP as clinical biomarkers Time: 2021Description: Differences in symptom, antibiotic treatment, acute complications, radiologic exams admission rate and length of stay between cases with viral, bacterial, atypical bacterial and mixed viral-bacterial infection
Measure: Descriptive statistics of study cohort with regard to etiologic agent Time: 2020Description: Differences in symptom, antibiotic treatment, acute complications, radiologic exams admission rate and length of stay between cases who tested positive for respiratory virus by MariPOC® Respi as compared to those with a negative test
Measure: Evaluation of MariPOC® Respi in a clinical setting Time: 2022Description: Number of hospital-requiring respiratory infections in cases and controls
Measure: Assessment of long-term outcomes of children with CAP Time: 2027Description: Difference in asthma prevalence between cases with viral and bacterial clinical CAP as compared to an estimate of the prevalence in the general population
Measure: Assessment of long-term outcomes of children with CAP Time: 2027Description: Difference in proportion of hospital-requiring respiratory infections between cases with viral, bacterial, atypical and mixed viral-bacterial infection
Measure: Assessment of long-term outcomes of children with CAP Time: 2027Description: Difference in MxA-levels between PCR+/MariPOC® Respi+ and PCR+/MariPOC® Respi- study subjects.
Measure: Evaluation of MariPOC® Respi Time: 2022Description: Estimation of etiology of cases using two levels of certainty (definitive as well as probable definition).
Measure: Etiology of cases in TREND study Time: 2020The aim of this study is to test whether Traditional Chinese Medicines (TCMs) are effective and safe for treating COVID-19 infection. After the enrolment of approximately 30 subjects, the recruitment will be paused, and planned interim analysis will be performed to preliminarily investigate the efficacy and safety of TCMs in patients infected with COVID-19.
Description: The incidence rate of acute respiratory distress syndrome (ARDS) development
Measure: The incidents of acute respiratory distress syndrome (ARDS) development Time: 14 daysDescription: Time to complete remission of fever in eligible subjects
Measure: The time to fever resolution rate Time: 14 daysDescription: improvement of chest radiographic evidence indirectly reflects recovery in patients infected with COVID-19.
Measure: Time to recovery of lung injury Time: 14 daysDescription: The rate of subject who die will be described.
Measure: Rate of subjects who die Time: 28 daysDescription: The rate of subjects with severe 2019-nCoV infection who receive systematic corticosteroids will be described.
Measure: Rate of subjects receiving systematic corticosteroids Time: 28 daysDescription: The length of hospital stays
Measure: The length of hospital stays Time: 28 daysDescription: The duration of respiratory support including invasive and non-invasive mechanical ventilation
Measure: The duration of respiratory support Time: 28 daysThe SARS-CoV-2 infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. There is no confirmed antivirus therapy for people infected SARS-CoV-2, most of them should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions. This clinical trial is to inspect the safety and efficiency of Mesenchymal Stem Cells (MSCs) therapy for pneumonia patients infected with SARS-CoV-2.
Description: Evaluation of Pneumonia Improvement
Measure: Size of lesion area by chest radiograph or CT Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21,Day 28Description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measure: Side effects in the MSCs treatment group Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180Description: Evaluation of Pneumonia Improvement
Measure: Improvement of Clinical symptoms including duration of fever and respiratory Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28Description: Marker for COVID-19
Measure: Time of nucleic acid turning negative Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180Description: Marker for efficacy of treatment
Measure: Rate of mortality within 28-days Time: Day 28Description: Marker of Immunological function
Measure: CD4+ and CD8+ T celll count Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180Description: Markers of organ function
Measure: Alanine aminotransferase Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180Description: Markers of Infection
Measure: C-reactive protein Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180Description: Markers of organ function
Measure: Creatine kinase Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180The study aims to evaluate the efficacy and safety of darunavir and cobistastat in the treatment of COVID-19 pneumonia
Description: The diagnosis of critical illness case was based on the notice on printing and distributing the diagnosis and treatment plan of pneumonia with new coronavirus infection (trial version 4) made by National Health Commission of the People's Republic of China.
Measure: The critical illness rate of subjects at weeks 2 Time: 14 days after randomizationAt present, there is no specific and effective antiviral therapy.In this study, an open, prospective/retrospective, randomized controlled cohort study was designed to compare the efficacy of two therapeutic schemes(abidol hydrochloride,abidol hydrochloride combined with interferon atomization)in the treatment of 2019-nCoV viral pneumonia, so as to provide reliable evidence-based medicine for the treatment of viral pneumonia caused by 2019-nCoV.
Description: A: For mild patients : fever, cough and other symptoms relieved with improved lung CT; B:For severe patients : fever, cough and other symptoms relieved with improved lung CT,SPO2> 93% or PaO2/FiO2> 300mmHg (1mmHg=0.133Kpa);
Measure: Rate of disease remission Time: two weeksDescription: Compare the average time of lung imaging recovery after 2 weeks of treatment in each group.
Measure: Time for lung recovery Time: two weeksAt present, there is no specific and effective antiviral therapy.In this study, an open, prospective/retrospective, randomized controlled cohort study was designed to compare the efficacy of three antiviral drugs in the treatment of 2019-nCoV pneumonia by studying the efficacy of abidol hydrochloride, oseltamivir and lopinavir/ritonavir in the treatment of 2019-nCoV viral pneumonia, and to explore effective antiviral drugs for new coronavirus. To provide reliable evidence-based medicine basis for the treatment of viral pneumonia caused by new coronavirus infection.
Description: A: For mild patients : fever, cough and other symptoms relieved with improved lung CT; B:For severe patients : fever, cough and other symptoms relieved with improved lung CT,SPO2> 93% or PaO2/FiO2>300mmHg (1mmHg=0.133Kpa);
Measure: Rate of disease remission Time: two weeksDescription: Compare the average time of lung imaging recovery after 2 weeks of treatment in each group.
Measure: Time for lung recovery Time: two weeksDue to the outbreak of 2019 Novel Coronavirus Pneumonia in Wuhan, Hubei province, medical staff and residents are facing great psychological pressure, the investigator plan to use electronic questionnaire to carry out investigation research.
Description: GHQ-12(general health questionnaire-12): minimal score 0, maximal score 12, higher scores mean a better or worse outcome.
Measure: GHQ-12(general health questionnaire-12) Time: 2 weeksDescription: IES-R(Impact of Event Scale-Revised):score range:0-88, the higher the worse
Measure: IES-R(Impact of Event Scale-Revised) Time: 2 weeksIn the absence of 2019-ncov specific therapeutic drugs, arbidol is effective against a variety of coronaviruses in vitro pharmacodynamics. In order to observe the efficacy and safety of arbidol in the treatment of 2019-ncov infected pneumonia, this study is planned.
Description: virus negative conversion rate in second week, overall virus negative conversion rate
Measure: Virus negative conversion rate Time: 14-20 daysDescription: defined as: the rate of Axillary temperature ≤37.5 ℃ for at least 48h
Measure: Antipyretic rate Time: 14-20 daysDescription: time to relieve symptoms of fever, cough, dyspnea, myalgia, etc
Measure: Symptom relief time Time: 14-20 daysDescription: no adjuvant oxygen therapy, resting oxygen saturation>95%, oxygenation index>350
Measure: Finger oxygen improvement rate Time: 14-20 daysDescription: Mild, common type progression to severe or critical illness rate
Measure: Disease progression rate Time: 14-20 daysBased on oseltamivir treatment, evaluate the efficacy and safety of ASC09/ritonavir compound tablets(ASC09F) or ritonavir tablets for 2019-nCoV infection patients.
Description: The definition of comprehensive adverse outcome is as follows: SPO2≤93% without oxygen inhalation; PaO2/FiO2≤300mmHg; RR≥30 bpm without oxygen inhalation.
Measure: Rate of comprehensive adverse outcome Time: 14 daysDescription: The definition of clinical remission: Based on the symptoms of the disease (fever,cough,diarrhea,myalgia,dyspnea) has been relieved for 48 hours; There is no evidence of disease progression(New dyspnea, SpO2 decreased≥3%,RR≥30 bpm without oxygen inhalation).
Measure: Time of clinical remission Time: 28 daysIn this single-center, randomized, open-label, controlled study, the investigators will evaluate the efficacy and safety of Intravenous Immunoglobulin (IVIG) in combination with standard care for severe 2019 novel coronavirus (2019-nCoV) pneumonia.
Description: A decline of 2 points on the 7-point scale from admission means better outcome. The 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death).
Measure: Clinical improvement based on the 7-point scale Time: 28 days after randomizationDescription: Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition.
Measure: Lower Murray lung injury score Time: 7 days after randomizationDescription: Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition.
Measure: Lower Murray lung injury score Time: 14 days after randomizationDescription: Number of deaths during study follow-up
Measure: 28-day mortality Time: Measured from Day 0 through Day 28Description: Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up.
Measure: Duration of mechanical ventilation Time: Measured from Day 0 through Day 28Description: Days that a participant spent at the hospital. Multiple hospitalizations are summed up.
Measure: Duration of hospitalization Time: Measured from Day 0 through Day 28Description: Proportion of patients with negative RT-PCR results of virus in upper and/or lower respiratory tract samples.
Measure: Proportion of patients with negative RT-PCR results Time: 7 and 14 days after randomizationDescription: Proportion of patients in each category of the 7-point scale, the 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death).
Measure: Proportion of patients in each category of the 7-point scale Time: 7,14 and 28 days after randomizationDescription: Proportion of patients with different inflammation factors in normalization range.
Measure: Proportion of patients with normalized inflammation factors Time: 7 and 14 days after randomizationDescription: Frequency of Adverse Drug Events
Measure: Frequency of Adverse Drug Events Time: Measured from Day 0 through Day 28Description: Frequency of Serious Adverse Drug Events
Measure: Frequency of Serious Adverse Drug Events Time: Measured from Day 0 through Day 28The study aims to evaluate the efficacy and safety of hydroxychloroquine in the treatment of COVID-19 pneumonia.
Description: The diagnosis of critical illness case was based on the notice on printing and distributing the diagnosis and treatment plan of pneumonia with new coronavirus infection (trial version 4) made by National Health Commission of the People's Republic of China.
Measure: The critical illness rate of subjects at weeks 2 Time: 14 days after randomizationAt present, there is no specific and effective antiviral therapy.In this study, an open, prospective/retrospective, randomized controlled cohort study was designed to compare the efficacy of different hormone doses in the treatment of 2019-nCoV severe Pneumonia.This study explores effective treatment programs for 2019-nCoV severe pneumonia and provides a reliable evidence-based basis for the treatment.
Description: For mild patients: disease remission refers to relieved symptoms with improved lung CT; For severe patients: disease remission refers to relieved symptoms with improved lung CT; or SPO2>93% or PaO2/FiO2 >300mmHg.
Measure: Rate of disease remission Time: day 7Description: the critical stage refers to respiratory failure that occurs and requires mechanical ventilation, shock, or having other organ failure that needs ICU monitoring and treatment.
Measure: Rate and time of entering the critical stage Time: day 7Description: Rate of patients without fever at day 7
Measure: Rate of normal tempreture Time: day 7Description: Rate of patients with respiratory symptom remission at day 7
Measure: Rate of respiratory symptom remission Time: day 7Description: Rate of patients with lung imaging recovery at day 7
Measure: Rate of lung imaging recovery Time: day 7Description: Rate of patients with laboratory indicator recovery at day 7
Measure: Rate of laboratory indicator recovery Time: day 7Description: Rate of patients withundetectable viral RNA at day 7
Measure: Rate of undetectable viral RNA Time: day 72019 new coronavirus (2019-nCoV) infected pneumonia, namely severe acute respiratory infection (SARI) has caused global concern and emergency. There is a lack of effective targeted antiviral drugs, and symptomatic supportive treatment is still the current main treatment for SARI. Vitamin C is significant to human body and plays a role in reducing inflammatory response and preventing common cold. In addtion, a few studies have shown that vitamin C deficiency is related to the increased risk and severity of influenza infections. We hypothize that Vitamin C infusion can help improve the prognosis of patients with SARI. Therefore, it is necessary to study the clinical efficacy and safety of vitamin C for the clinical management of SARI through randomized controlled trials during the current epidemic of SARI.
Description: days without ventilation support during 28 days after patients' enrollment
Measure: Ventilation-free days Time: on the day 28 after enrollmentDescription: wether the patient survives
Measure: 28-days mortality Time: on the day 28 after enrollmentDescription: days of the patients staying in the ICU
Measure: ICU length of stay Time: on the day 28 after enrollmentDescription: the rate of CPR
Measure: Demand for first aid measuments Time: on the day 28 after enrollmentDescription: days of using vasopressors
Measure: Vasopressor days Time: on the day 28 after enrollmentDescription: P O2/Fi O2 which reflects patients' respiratory function
Measure: Respiratory indexes Time: on the day 10 and 28 after enrollmentDescription: Ecmo or ventilator
Measure: Ventilator parameters Time: on the day 10 and 28 after enrollmentDescription: Acute Physiology and Chronic Health Evaluation
Measure: APACHE II scores Time: on the day 10 after enrollmentDescription: Sepsis-related Organ Failure Assessment
Measure: SOFA scores Time: on the day 10 after enrollmentThe new coronavirus pneumonia is an acute infectious pneumonia. The pathogen is a previously unknown new coronavirus, namely 2019 new coronavirus (2019 novel coronavirus, 2019 nCoV). However, there is no specific anti-viral drug. It has been found that the specific antibodies against virus antigen are produced after these patients were cured, which could block the infection of 2019 nCoV on the host cells. At present, immunoadsorption is the most direct, rapid and effective method to separate immunoglobulin from the cured patients. Therefore, the study aims to prepare the immunoglobulin from 2019-ncov pneumonia cured patients, evaluate the efficacy and safety of the immunoglobulin in 2019-ncov pneumonia cured patients on the treatment of acute severe 2019-ncov pneumonia, and provide a new strategy for the treatment of 2019-ncov pneumonia.
Description: TTCI is defined as the time (in days) from initiation of study treatment (active or placebo) until a decline of two categories from admission status on a six-category ordinal scale of clinical status which ranges from 1 (discharged) to 6 (death). Six-category ordinal scale: 6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.
Measure: Time to Clinical Improvement (TTCI) Time: up to 28 daysDescription: on days 7, 14, 21, and 28
Measure: Clinical status assessed by the ordinal scale Time: up to 28 daysDescription: 1. No need for supplemental oxygenation; 2. nasal cathete oxygen inhalation;3. Mask oxygen inhalation;4. Noninvasive ventilator oxygen supply;5. Invasive ventilator oxygen supply.
Measure: The differences in oxygen intake methods Time: up to 28 daysDescription: The detection frequency could be increased according to clinician's decision
Measure: The lesions of the pulmonary segment numbers involved in pulmonary CT [ every 7 days] Time: up to 28 daysDescription: The antibody titer is detected on days 3 and 28
Measure: Dynamic changes of 2019-nCoV antibody titer in blood Time: up to 28 daysSerious Pneumonia and Critical Pneumonia caused by the 2019-nCOV infection greatly threats patients' life, UC-MSCs treatment has been proved to play a role in curing multiple diseases. And this study is conducted to find out whether or not it will function in 2019-nCOV infection Pneumonia.
Description: partial arterial oxygen pressure (PaO2) / oxygen concentration (FiO2)
Measure: Oxygenation index Time: on the day 14 after enrollmentDescription: whether the patient survives
Measure: 28 day mortality Time: on the day 28 after enrollmentDescription: days of the patients in hospital
Measure: Hospital stay Time: up to 6 monthsDescription: whether or not the 2019-nCoV nucleic acid test is positive
Measure: 2019-nCoV nucleic acid test Time: on the day 7,14,28 after enrollmentDescription: whether lung imaging examinations show the improvement of the pneumonia
Measure: Improvement of lung imaging examinations Time: on the day 7,14,28 after enrollmentDescription: counts of white blood cell in a litre of blood
Measure: White blood cell count Time: on the day 7,14,28 after enrollmentDescription: counts of lymphocyte in a litre (L) of blood
Measure: Lymphocyte count Time: on the day 7,14,28 after enrollmentDescription: percentage of lymphocyte in white blood cell
Measure: Lymphocyte percentage Time: on the day 7,14,28 after enrollmentDescription: procalcitonin in microgram(ug)/L
Measure: Procalcitonin Time: on the day 7,14,28 after enrollmentDescription: IL-2 in picogram(pg)/millilitre(mL)
Measure: interleukin(IL)-2 Time: on the day 7,14,28 after enrollmentDescription: IL-4 in pg/mL
Measure: IL-4 Time: on the day 7,14,28 after enrollmentDescription: IL-6 in pg/mL
Measure: IL-6 Time: on the day 7,14,28 after enrollmentDescription: IL-8 in pg/mL
Measure: IL-8 Time: on the day 7,14,28 after enrollmentDescription: IL-10 in pg/mL
Measure: IL-10 Time: on the day 7,14,28 after enrollmentDescription: TNF-α in nanogram(ng)/L
Measure: tumor necrosis factor(TNF)-α Time: on the day 7,14,28 after enrollmentDescription: γ-IFN in a thousand unit (KU)/L
Measure: γ-interferon(IFN) Time: on the day 7,14,28 after enrollmentThere is still controversy about the effective of glucocorticoids for the treatment of novel coronavirus pneumonia. This is a prospective randomized controlled trails. The aim is to explore the effectiveness and safety of glucocorticoids in the treatment of novel coronavirus pneumonia.
Description: The clinical symptoms and signs continue to deteriorate, or new pulmonary or extrapulmonary lesions appear, or the chest imaging indicates the progress, and the patient is transferred to ICU or intubation and invasive ventilation or died.
Measure: the incidence of treatment failure in 14 days Time: 14 daysDescription: The clinical symptoms and signs improved or alleviated (the temperature be normal , respiratory symptoms improved significantly, imaging showed obvious absorption) and no additional or alternative treatment was needed.
Measure: clinical cure incidence in 14 days Time: 14 daysDescription: the duration from admission to virus negative
Measure: the duration of virus change to negative Time: 30 daysDescription: the patient die in 30 days
Measure: mortality at day 30 Time: 30 daysDescription: the patients transform to ICU because of clinical deteriorate in 30 days
Measure: ICU admission rate in 30 days Time: 30 daysIn December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay. In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of lung injury caused by COVID-19 can be an alternative target for current treatment. Thalidomide has anti-inflammatory, anti-fibrotic, anti-angiogenesis, and immune regulation effects. This study is the first Prospective, Multicenter, Randomized, Double-blind, Placebo, Parallel Controlled Clinical Study at home and abroad to use immunomodulators to treat patients with COVID-19 infection.
Description: TTCR is defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, and oxygen saturation, and alleviation of cough, sustained for at least 72 hours. Normalisation and alleviation criteria: Fever - ≤36.6°C or -axilla, ≤37.2 °C oral or ≤37.8°C rectal or tympanic, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.
Measure: Time to Clinical recoveryTime to Clinical Recovery (TTCR) Time: up to 28 daysDescription: baseline SpO2 during screening, PaO2/FiO2 <300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen
Measure: All cause mortality Time: up to 28 daysDescription: Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support.
Measure: Frequency of respiratory progression Time: up to 28 daysDescription: in those with fever at enrolment
Measure: Time to defervescence Time: up to 28 daysDescription: in those with cough at enrolment rated severe or moderate
Measure: Time to cough reported as mild or absent Time: up to 28 daysDescription: patients with moderate / severe dyspnea when enrolled
Measure: Respiratory improvement time Time: up to 28 daysThe novel coronavirus pneumonia is a kind of new emerging respiratory infectious disease, characterized by fever, dry cough, and chest tightness, and caused by the infection of the 2019 novel coronavirus (2019-nCoV). In severe cases, there will be rapid respiratory system failure. The novel coronavirus pneumonia is extremely contagious and the disease progresses rapidly. It has become a urgent and serious public health event that threatens human life and health globally. Among them, severe pneumonia caused by novel coronavirus is characterized by extensive acute inflammation of the lungs and the patient is critically ill. At present, there is no effective treatment in clinical practice.Most of them should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions. This clinical trial is to inspect the safety and efficiency of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for severe pneumonia patients infected with 2019-nCoV.
Description: Evaluation of Pneumonia Improvement
Measure: Pneumonia severity index Time: From Baseline (0W) to 12 week after treatmentDescription: Evaluation of Pneumonia Improvement
Measure: Oxygenation index (PaO2/FiO2) Time: From Baseline (0W) to 12 week after treatmentDescription: Incidence of acute and chronic treatment-related adverse events in patients with novel coronavirus severe pneumonia receiving UC-MSCs infusion as assessed.
Measure: Side effects in the UC-MSCs treatment group Time: From Baseline (0W) to 96 week after treatmentDescription: Marker for efficacy of treatment
Measure: 28-days survival Time: Day 28Description: Markers of organ function(Score each criterion on a scale of 0 to 4, and the higher the score, the worse the prognosis.)
Measure: Sequential organ failure assessment Time: Day 28Description: Markers of Infection
Measure: C-reactive protein Time: From Baseline (0W) to 12 week after treatmentDescription: Markers of Infection
Measure: Procalcitonin Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: Lymphocyte count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD3+, CD4+ and CD8+ T celll count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD4+/CD8+ratio Time: From Baseline (0W) to 12 week after treatmentCompare the efficacy and safety of Bromhexine Hydrochloride Tablets combined with standard treatment/ standard treatment in patients with suspected and mild, or common novel coronavirus pneumonia (COVID-19). Random, open, group sequential design.
Description: Defined as random to fever, respiratory rate return to normal and cough remission over 48 hours.
Measure: Time to clinical recovery after treatment Time: within 14 days from the start of medicationDescription: Aggravation was defined as(one of them): respiratory distress, RR ≥ 30 times / min; SpO2 ≤ 93% in resting state; arterial partial pressure of oxygen (PaO2) /concentration of oxygen (FiO2) ≤ 300mmHg
Measure: Rate of aggravation Time: within 14 days from the start of medicationDescription: Clinical remission was defined as (one of them): sustained (more than 48 hours) alleviation of illness based on symptom (fever, cough, dyspnea, myalgia, diarrhea and so on) all being absent and no evidence for progression.
Measure: Clinical remission rate Time: within 14 days from the start of medicationDescription: oxygenation index
Measure: Dynamic changes of oxygenation index Time: within 14 days from the start of medicationDescription: time of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery
Measure: Time to cure Time: within 14 days from the start of medicationDescription: proportion of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery among infected patients
Measure: rate to cure Time: within 14 days from the start of medicationDescription: defervescence is defined as below 37 Celcius degrees(ear temperature)
Measure: Time to defervescence Time: within 14 days from the start of medicationTo evaluate the safety and efficacy of humanized Meplazumab for Injection in patients infected by 2019-nCoA.
Description: Virological clearance rate using Real-Time PCR in upper and/or lower respiratory tract samples at day 3, day 7 and day 14 respectively.
Measure: 2019 nCoV nucleic acid detection Time: 14 daysDescription: Time (days) from initiation of Meplazumab treatment until normalization of body temperature (≤37℃ axilla)
Measure: Recovery of body temperature Time: 14 daysDescription: Time (days) from initiation of Meplazumab treatment until normalization of resting respiratory rate (≤24/min)
Measure: Recovery of resting respiratory rate Time: 14 daysDescription: Time (days) from initiation of Meplazumab treatment until normalization of SPO2 (>94%)
Measure: Recovery of SPO2 Time: 14 daysDescription: Rate of lung imaging recovery
Measure: Chest CT / chest film changes Time: 28 daysDescription: Rate of PaO2 / FiO2 recovery
Measure: PaO2 / FiO2 Time: 14 daysDescription: Days to reach the isolation release standard
Measure: Time to reach the isolation release standard Time: 28 daysDescription: Rate of CRP, D-Dimer test recovery
Measure: Changes of inflammatory immune status Time: 14 daysthe investigators conduct a randomized, open-label trial to evaluate and compare the safety and efficacy of Xiyanping injection in patients with 2019-nCoV pneumonia.
Description: From the beginning of study drug use to fever, respiratory rate, blood oxygen saturation to normal and cough relief, and maintained for at least 72 hours or more, calculated in hours
Measure: Clinical recovery time Time: Up to Day 14Description: From the beginning of research drug use to body temperature <37.3 ℃ (underarm) or mouth temperature ≤37.5 ° C, or anal or ear temperature ≤37.8 ° C, and maintained for 24h or more
Measure: Complete fever time Time: Up to Day 14Description: Cough score "day + night" from the beginning of study medication to cough ≤ 1 point, and maintained for 24 hours and above
Measure: Cough relief time Time: Up to Day 14Description: From the beginning of the study drug to two consecutive times (sampling interval of at least 1 day)
Measure: Virus negative time Time: Up to Day 14Description: Defined as the proportion of subjects exacerbated during treatment and meeting the diagnostic criteria for severe or critical neocoronavirus pneumonia
Measure: Incidence of severe or critical neocoronavirus pneumonia Time: Up to Day 14The novel identified coronavirus (SARS-CoV-2) in 2019 causes an nationwide outbreak as well as public health crisis in China, and expands globally. Pulmonary edema is one of the most detrimental symptoms and usually presents in severe and critical coronavirus disease (COVID-19), resulting in dyspnea, acute lung injury (ALI) ,acute respiratory distress syndrome (ARDS), and even death. Recent evidence revealed higher levels of blood Vascular Endothelial Growth Factor (VEGF) in COVID-19 patients compared with healthy controls. VEGF is considered as the most potent vascular permeability inducers. Numerous studies have revealed that VEGF was a key factor and a potential therapeutic target in ALI and ARDS. Bevacizumab, an anti-VEGF drug, approved by the FDA on February 26, 2004 and widely used in clinical oncotherapy, is a promising drug for ALI/ARDS in COVID-19 through suppression of pulmonary edema.
Description: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio
Measure: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio Time: 24 hoursDescription: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio
Measure: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio Time: 72 hoursDescription: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio
Measure: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio Time: 7 daysDescription: Liker scale: The patient grades his current breathing compared to when he first started the drug (from -3 to 3). "0" = no change, "1" =minimally better, "2" =moderately better, "3" =markedly better, "-1" =minimally worse, "-2" =moderately worse, "-3" =markedly worse
Measure: Degree of dyspnea (Liker scale) Time: 72 hoursDescription: The patient grades the current breathing condition of himself compared to when he first started the drug (from -3 to 3).
Measure: Degree of dyspnea (Liker scale) Time: 7 daysDescription: Visual analog scale (VAS): The patient draws a horizontal line on an axial graph (from 0 to 100) to show the degree of how he feels about breathing. The number "0" equals the worst breathing the patient has ever felt and the number "100" equals the best he has ever felt.
Measure: Degree of dyspnea (VAS) Time: 72 hoursDescription: Visual analog scale (VAS): The patient draws a horizontal line on an axial graph (from 0 to 100) to show the degree of how he feels about breathing. The number "0" equals the worst breathing the patient has ever felt and the number "100" equals the best he has ever felt.
Measure: Degree of dyspnea (VAS) Time: 7 daysDescription: The degree of exudation on Chest CT
Measure: The area of lung lesions on Chest CT Time: 7 daysDescription: The degree of lung exudation on Chest CT
Measure: The degree of lung exudation on Chest CT Time: 7 daysDescription: transcutaneous oxygen saturation
Measure: SpO2 Time: 24 hoursDescription: transcutaneous oxygen saturation
Measure: SpO2 Time: 72 hoursDescription: transcutaneous oxygen saturation
Measure: SpO2 Time: 7 daysDescription: Partial arterial oxygen pressure
Measure: PaO2 Time: 24 hoursDescription: Partial arterial oxygen pressure
Measure: PaO2 Time: 72 hoursDescription: Partial arterial oxygen pressure
Measure: PaO2 Time: 7 daysDescription: CRP
Measure: CRP Time: 72 hoursDescription: CRP
Measure: CRP Time: 7 daysDescription: hs-CRP
Measure: hs-CRP Time: 72 hoursDescription: hs-CRP
Measure: hs-CRP Time: 7 daysDescription: All-cause mortality
Measure: All-cause mortality Time: 7 daysDescription: All-cause mortality
Measure: All-cause mortality Time: 14 daysIn December 2019, a novel coronavirus infectious disease characterized by acute respiratory impairment due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan city of Hubei province in China. So far no specific antiviral therapy can be available for patients with SARS-CoV-2 infection. Although symptomatic and supportive care, even with mechanical ventilation or extracorporeal membrane oxygenation (ECMO), are strongly recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes. This pilot clinical trial will be performed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in severe patients with novel coronavirus pneumonia (NCP).
Description: Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)
Measure: Adverse reaction (AE) and severe adverse reaction (SAE) Time: Up to 28 daysDescription: Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)
Measure: Time to clinical improvement (TTIC) Time: Up to 28 daysDescription: Number of patients weaning from mechanical ventilation within 28 days
Measure: Number of patients weaning from mechanical ventilation Time: Up to 28 daysDescription: Duration (days) of ICU monitoring within 28 days
Measure: Duration (days) of ICU monitoring Time: Up to 28 daysDescription: Duration (days) of vasoactive agents using within 28 days
Measure: Duration (days) of vasoactive agents usage Time: Up to 28 daysDescription: Duration (days) of mechanical ventilation supply among survivors
Measure: Duration (days) of mechanical ventilation supply Time: Up to 28 daysDescription: Number of patients with improved organ failure within 28 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs
Measure: Number of patients with improved organ failure Time: Up to 28 daysDescription: Rate of mortality within 28 days
Measure: Rate of mortality Time: Up to 28 daysDescription: Records of daily sequential organ failure assessment (SOFA) score (From 0 to 24 points, higher scores mean a worse outcome)
Measure: Sequential organ failure assessment (SOFA) score Time: Every day for 28 daysDescription: Records of Blood routine test
Measure: Lymphocyte Count (10E9/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Coagulation function
Measure: D-dimer (mg/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Records of heart failure
Measure: pro-type B natriuretic peptide (pro-BNP) (pg/ml) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Record of serum cytokine
Measure: IL-1β (pg/ml) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Record of serum cytokine
Measure: IL-2R (ng/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Record of serum cytokine
Measure: IL-6 (ng/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Record of serum cytokine
Measure: IL-8 (ng/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Computed tomography or X-ray
Measure: Chest imaging Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Time to SARS-CoV-2 RT-PCR negativity in respiratory tract specimens
Measure: Time to SARS-CoV-2 RT-PCR negativity Time: Up to 28 daysSince december 2019, acute respiratory disease due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. There is no confirmed antivirus therapy for 2019-nCoV infection. Natural killer (NK) cells are innate lymphocytes that may serve as useful effectors against danger infection. The purpose of this clinical investigation is to evaluate the safety and efficiency of NK Cells in combination with standard therapy for pneumonia patients infected with 2019-nCoV.
Description: Evaluation of pneumonia improvement
Measure: Improvement of clinical symptoms including duration of fever Time: Measured from day 0 through day 28Description: Evaluation of pneumonia improvement
Measure: Improvement of clinical symptoms including respiratory frequency Time: Measured from day 0 through day 28Description: Safety evaluation
Measure: Number of participants with treatment-related adverse events evaluated with CTCAE,version 4.0 Time: Measured from day 0 through day 28Description: Marker for 2019-nCoV
Measure: Time of virus nucleic acid test negative Time: Measured from day 0 through day 28Description: Marker of immunological function
Measure: CD4+ and CD8+ T cell count Time: Measured from day 0 through day 28Description: Marker for efficacy of treatment
Measure: Rate of mortality within 28-days Time: Day 28Description: Recovery of lung injury
Measure: Size of lesion area by thoracic imaging Time: Measured from day 0 through day 28Since Dec 2019, over 70000 novel coronavirus infection pneumonia (NCIP) patients were confirmed. 2019 novel coronavirus (2019 nCoV) is a RNA virus, which spread mainly from person-to-person contact. Most of the symptoms are non-specific, including fever, fatigue, dry cough. Sever NCIP patients may have shortness of breath and dyspnea, and progress to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). The mortality is reported to be around 2.3%. Thus, early detection and early treatment is very important to the improvement of NCIP patients' prognosis. At present, NCIP RNA detection of pharyngeal swab specimen by RT-PCR is recommended. However, due to the universal susceptibility to 2019 nCoV in general population and limited number of NCIP RNA detection kits available, to identify an efficient screening strategy is urgently needed. This study aim to develop and validate the diagnostic accuracy and screening efficiency of a new NCIP screening strategy, which can benefit the disease prevention and control.
Description: The screening accuracy of the two screening strategies were calculated and compared.
Measure: Screening accuracy Time: 1 monthDescription: The costs of the two screening strategies were recorded. Cost-effectiveness analysis were performed and compared.
Measure: Cost-effectiveness analysis Time: 1 monthThe acute lung injury caused by SARS and 2003 were both related to the inflammatory cytokine storm in patients. The biochemical test showed abnormal increase in related indicators such as interleukin-8, and CT images showed a medical "white" lung". According to the experience of SARS treatment in 2003, the use of hormones will indeed help the patients to alleviate their illness, but patients who survived SARS either had too much hormone at that time and took too long. Although the lungs could recover, but the femoral head was necrotic Either the amount of hormones was very conservative at the time, which kept the lungs in the storm of inflammatory factors, leading to the emergence of irreversible pulmonary fibrosis. So is there a medicine that can anti-inflammatory, reduce the load of hormone use, and have the effect of treating and preventing pulmonary fibrosis complicated by severe viral lung? At present, pirfenidone has achieved encouraging results in the treatment of idiopathic Pulmonary Fibrosis (CTD-ILD) diseases. It is particularly encouraging that the values announced at the 2019 ATS Annual Conference suggest that pirfenidone has more anti-inflammatory and anti-oxidant effects than its own outstanding anti-fibrotic ability. The data shows early use, Its strong anti-SOD activity can effectively inhibit IL-1beta and IL-4, and can open the prevention mode of pulmonary interstitial fibrosis. Based on the above, this project intends to make the following scientific assumptions: based on the homology of the pathogens of the new coronavirus-infected pneumonia and the coronavirus infection of pneumonia in 2003, the similarities in the occurrence and development of the disease, that is, the pulmonary inflammatory storm occurs first, and thereafter The progress of fibrosis and the progressive decline of lung function and mortality are higher than those of ordinary pneumonia. We hope that by adding pirfenidone as a treatment program in addition to standard treatment, it will be a new and severe type of coronavirus infection. Patient clinical treatment provides an effective and practical method.
Description: Lesion area of chest CT image at 4 weeks
Measure: chest CT Time: 4 weeksDescription: Absolute change in pulse oxygen from baseline
Measure: Finger pulse oxygen Time: 4 weeksDescription: Absolute change in blood gas from baseline
Measure: blood gas Time: 4 weeksDescription: Absolute change in total score of King's brief questionnaire for interstitial Absolute change in total score of King's brief questionnaire for interstitial pulmonary disease (k-bild) from baseline at week 4
Measure: K-BILD Time: 4 weeksDescription: Time to death within 4 weeks due to respiratory problems
Measure: death Time: 4 weeksDescription: Time to disease progression or death within 4 weeks
Measure: Time to disease progression or death within 4 weeks Time: 4 weeksDescription: lymphocyte count
Measure: blood Time: 4 weeksDescription: Absolute change in viral nucleic acid from baseline
Measure: viral nucleic acid Time: 4 weeksDescription: Pulmonary fibrosis survival symptoms absolute changes in dyspnea score from baseline
Measure: dyspnea score Time: 4 weeksDescription: changes in blood inflammatory indexes
Measure: blood Time: 4 weeksDescription: Absolute change in cough scores for pulmonary fibrosis survival symptoms from baseline
Measure: cough scores Time: 4 weeksTo develop practical and effective clinical diagnosis and treatment schemes for the control of novel coronavirus pneumonia.
Description: Number of patients recover from novel coronavirus pneumonia
Measure: recovery Time: up to 24 weeksWhile 2019-nCoV nucleic acid swab tests has high false positives rate, How to diagnose 2019-nCoV pneumonia and predict prognosis by CT is very important.In this retrospective single-center study, we consecutively included suspected 2019-nCoV pneumonia critical cases in the intensive care unit of Wuhan third hospital from January 31, 2020 to February 16, 2020. The cases were confirmed by real-time RT-PCR, and all patients were evaluated with CT, cutoff values were obtained according to the Yoden index, and were divided into high CT score group and low CT score group. Epidemiological, demographic, clinical, and laboratory data were collected.
This is an open-label, randomized, blank-controlled treatment clinical study. The objective of this study is to investigate the effect of T89 on improving oxygen saturation and clinical symptoms in patients with Coronavirus Disease 2019 (COVID-19). In this study, estimated total of 120-240 male and female patients who have been diagnosed with non-critical type of coronavirus pneumonia (COVID-19) will be enrolled and randomly assigned to one of two study groups, the T89 treatment group and the blank control group, to T89 or nothing on the base of a recommended standard treatment for up to 14 days . The primary efficacy parameters include the time to oxygen saturation recovery to normal level (≥97%), the proportion of patients with normal level of oxygen saturation after treatment, and the total duration of oxygen inhalation, oxygen flow change by time, oxygen concentration change by time during treatment.
Description: From screening to the end of treatment, for all patients randomized, oxygen saturation will be assessed for 3 times daily, the time to oxygen saturation recovery to normal level (≥97%) will be calculated finally based on that record and compared between two groups.
Measure: The time to oxygen saturation recovery to normal level (≥97%) Time: Day -1 to 10Description: The proportion of patients with normal level of oxygen saturation(≥97%) after treatment will be calculated finally based on that record and compared between two groups.
Measure: The proportion of patients with normal level of oxygen saturation(≥97%) Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the symptoms will be assessed 2 times daily, and the time to achievement of remission for each symptom will be calculated finally based on the record and compared between two groups.
Measure: The degree of remission of symptoms of patients, including: fatigue, nausea, vomiting, chest tightness, shortness of breath, etc. Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, myocardial enzyme spectrum will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the myocardial enzyme spectrum recovery to normal will be calculated finally based on the record and compared between two groups.
Measure: The time to the myocardial enzyme spectrum recovery to normal after treatment Time: Day -1, 3, 7 and 10Description: From screening to the end of treatment, for all patients randomized, myocardial enzyme spectrum will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal myocardial enzyme spectrum after treatment will be calculated finally based on the record and compared between two groups.
Measure: The proportion of the patients with normal myocardial enzyme spectrum after treatment Time: Day -1, 3, 7 and 10Description: From screening to the end of treatment, for all patients randomized, 12-lead electrocardiogram will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the myocardial enzyme spectrum recovery to normal level will be calculated finally based on the record and compared between two groups.
Measure: The time to the electrocardiogram recovery to normal level after treatment Time: Day -1, 3, 7 and 10Description: From screening to the end of treatment, for all patients randomized, 12-lead electrocardiogram will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal electrocardiogram will be calculated finally based on the record and compared between two groups.
Measure: The proportion of the patients with normal electrocardiogram after treatment Time: Day -1, 3, 7 and 10Description: From screening to the end of treatment, for all patients randomized, the hemodynamics will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the hemodynamics recovery to normal will be calculated finally based on the record and compared between two groups.
Measure: The time to the hemodynamics recovery to normal after treatment Time: Day -1 and 10Description: From screening to the end of treatment, for all patients randomized, the hemodynamics will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal hemodynamics will be calculated finally based on the record and compared between two groups.
Measure: The proportion of the patients with normal hemodynamics after treatment Time: Day -1 and 10Description: From screening to the end of treatment, for all patients randomized, the clinical severity will be assessed 1 time daily. The time to exacerbation or remission of the disease will be calculated finally based on the record and compared between two groups.
Measure: The time to exacerbation or remission of the disease after treatment; Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the clinical severity will be assessed 1 time daily. The proportion of patients whose disease get aggravated or alleviated will be calculated finally based on the record and compared between two groups.
Measure: The proportion of the patients with exacerbation or remission of disease after treatment Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the need for additional treatment will be recorded and compared between two groups.
Measure: The proportion of patients who need other treatment (e.g. heparin, anticoagulants) due to microcirculation disorders Time: Day -1 to 10Description: For all patients, the mortality will be recorded in each group and the rate will be compared between two groups.
Measure: The all-cause mortality rate Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the proportion of patients with acidosis will be compared between two groups based on the hemodynamics results.
Measure: The proportion of patients with acidosis Time: Day -1 and 10Description: For all patients, the duration of hospitalization will be recorded in each group and compared between two groups.
Measure: The total duration of the patients in-hospital Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the total duration of oxygen inhalation during oxygen treatment will be assessed and compared, if applicable, between two groups.
Measure: The total duration of oxygen inhalation during treatment Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the oxygen flow rate during oxygen treatment will be assessed and compared, if applicable, between two groups.
Measure: The oxygen flow rate during treatment Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the oxygen concentration during oxygen treatment will be assessed and compared, if applicable, between two groups.
Measure: The oxygen concentration during treatment Time: Day -1 to 10The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (COVID-19) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on COVID-19 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.
Description: The primary outcome will be the proportion of patients with mild COVID2019 who deteriorate to a severe form of the disease requiring intubation and mechanical ventilation. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.
Measure: Reduction in the incidence of intubation and mechanical ventilation Time: 28 daysDescription: Mortality from all causes
Measure: Mortality Time: 28 daysDescription: Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or a nasopahryngeal swab
Measure: Negative conversion of COVID-19 RT-PCR from upper respiratory tract Time: 7 daysDescription: Time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air) and alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent).
Measure: Time to clinical recovery Time: 28 daysObjects: The purpose of this study was to observe the characteristics of morbidity, disease progression and therapeutic effects of 2019-novel coronavirus pneumonia patients with different clinical types. Method: A single center, retrospective and observational study was used to collect COVID-19 patients admitted to Wuhan Infectious Diseases Hospital (Wuhan JinYinTan Hospital) from January 2020 to March 2020. The general information, first clinical symptoms, hospitalization days, laboratory examination, CT examination, antiviral drugs, immune enhancers, traditional Chinese medicine treatment and other clinical intervention measures were recorded, and the nutritional status and prognosis of the patients were recorded. confirm COVID-19 's disease progression, clinical characteristics, disease severity and treatment effects. To compare the characteristics of disease progression, clinical features, disease severity and therapeutic effect of different types of COVID-19. Outcomes: The characteristics of disease progression, clinical features, disease severity and therapeutic effect of different types of COVID-19. Conclusion: The characteristics of disease progression, clinical features and therapeutic effect of different types of COVID-19.
Description: The mortality of COVID-19 in 28 days
Measure: Mortality Time: 28 dayDescription: The time interval of COVID-19 form nucleic acid confirmed to the nucleic acid detection turn into negative.
Measure: The time interval of Nucleic acid detection become negative Time: 28 dayThe 2019 novel coronavirus pneumonia outbroken in Wuhan, China, which spread quickly to 26 countries worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, there is no effective treatment in clinical practice. The present clinical trial is to explore the safety and efficacy of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for novel coronavirus pneumonia patients.
Description: Evaluation of Pneumonia change
Measure: Size of lesion area by chest imaging Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Evaluation of Pneumonia change
Measure: Blood oxygen saturation Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Marker for efficacy of treatment
Measure: Rate of mortality within 28-days Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: 0-4 score, the higher the score is, the poor of the prognosis will be.
Measure: Sequential organ failure assessment Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Number of participants with treatment-related adverse events
Measure: Side effects in the UC-MSCs treatment group Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Markers of the heart function
Measure: Electrocardiogram, the changes of ST-T interval mostly Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Markers of infection
Measure: Concentration of C-reactive protein C-reactive protein, immunoglobulin Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Marker of Immunology and inflammation
Measure: CD4+ and CD8+ T cells count Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Marker of Immunology and inflammation
Measure: Concentration of the blood cytokine (IL-1β, IL-6, IL-8,IL-10,TNF-α) Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Markers of the heart function
Measure: Concentration of the myocardial enzymes Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay. In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of lung injury caused by COVID-19 can be an alternative target for current treatment. Xiyanping injection has anti-inflammatory and immune regulation effects. This study is a Randomized, Parallel Controlled Clinical Study to treat patients with COVID-19 infection.
Description: The time from study drug use to complete fever reduction and cough recovery is measured in hours.
Measure: Clinical recovery time Time: Up to Day 28To analyze the intubation with severe covid-19 pneumonia, the infection rate of anesthesiologist after intubation, and summarizes the experience of how to avoid the infection of anesthesiologist and ensure the safety of patients with severe covid-19 pneumonia.
Description: The data of Success rate of intubation with severe COVID-19 pneumonia patients
Measure: Success rate of intubation Time: the time span between 1hour before intubation and 24h after intubationDescription: Infection rate of Anesthesiologist who performed the endotracheal intubation for severe COVID-19 pneumonia patients
Measure: Infection rate of Anesthesiologist Time: the time span between 1hour before intubation and 14days after intubationDescription: Extubation time of intubated severe COVID-19 pneumonia patients
Measure: Extubation time Time: the time span between 1hour before intubation and 30days after intubationCurrently, the growing epidemic of a new coronavirus infectious disease (Covid-19) is wreaking havoc worldwide, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a RNA virus that display high similarity in both genomic and proteomic profiling with SARS-CoV that first emerged in humans in 2003 in China. Therefore, preventing and controlling the pandemic occurrences are extremely urgent as a global top priority. Due to the lack of effective antiviral drugs, patients may be treated by only addressing their symptoms such as reducing fever. Clinical autopsies from SARS-CoV-infected patients demonstrated that there were major pathological changes in the lungs, immune organs, and small systemic blood vessels with vasculitis. However, the detection of SARS-CoV were primarily found in the lung and trachea/bronchus, but was undetectable in spleen, lymph nodes, bone marrow, heart and aorta, highlighting the overreaction of immune responses induced by viral infection were really harmful, resulting in the pathogenesis of lungs, immune organs, and small systemic blood vessels. To this respect, immune modulation strategy may be potentially beneficial to enhance anti-viral immunity and efficiently reduce the viral load, improve clinical outcomes, expedite the patient recovery, and decline the rate of mortality in patients after being infected with SARS-CoV-2. Tianhe Stem Cell Biotechnologies Inc. has developed a novel globally-patented Stem Cell Educator (SCE) technology designed to reverse the autoimmune response in Type 1 diabetes (T1D), Alopecia Areata (AA) and other autoimmune diseases. SCE therapy uses human multipotent cord blood stem cells (CB-SC) from human cord blood. Their properties distinguish CB-SC from other known stem cell types, including mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC). Several clinical studies show that SCE therapy functions via CB-SC induction of immune tolerance in autoimmune T cells and restore immune balance and homeostasis in patients with T1D, AA and other inflammation-associated diseases. To correct the overreaction of overreaction of immune responses, the investigators plan to treat SARS-CoV-2 patients with Stem Cell Educator therapy.
Description: The feasibility will be evaluated by the number of Covid-19 patients who were unable to complete SCE Therapy.
Measure: Determine the number of Covid-19 patients who were unable to complete SCE Therapy Time: 4 weeksDescription: Measurements of immune markers' changes will be preformed by flow cytometry such as activated T cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.
Measure: Examine the percentage of activated T cells after SCE therapy by flow cytometry Time: 4 weeksDescription: Measurements of immune marker's changes will be preformed by flow cytometry such as the percentage of Th17 cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.
Measure: Assess the percentage of Th17 cells after SCE therapy by flow cytometry Time: 4 weeksDescription: Patients will be monitored for their chest imaging every 3 - 5 days for 4 weeks after receiving SCE therapy.
Measure: Chest imaging changes by computed tomography (CT) scan of the chest Time: 4 weeksDescription: To determine the viral load by real time RT-PCR, samples of blood, sputum, nose / throat swab will be collected from patients during the follow-up studies after receiving SCE therapy.
Measure: Quantification of the SARS-CoV-2 viral load by real time RT-PCR Time: 4 weeksEvaluation of novel coronavirus induced severe pneumonia by dental pulp mesenchymal stem cells
Description: Kaplan-meier method was used to calculate the median glassy shadow time in all subjects
Measure: Disppear time of ground-glass shadow in the lungs Time: 14 daysDescription: Kaplan-meier method was used to calculate the median lung shadow absorption of all subjects on 7, 14, 28, and 360 days
Measure: Absorption of Lung shadow absorption by CT Scan-Chest Time: 7, 14, 28 and 360 daysDescription: T test was used to compare the blood oxygen values of each subject at day 3, 7 and 14
Measure: Changes of blood oxygen Time: 3, 7 and 14 daysThe COVID-19 has a clustering morbidity trend and older people with chronic diseases are more likely to die, such as chronic renal insufficiency and chronic cardiovascular disease. We set up a COVID-19 pneumonia grading scale. The COVID-19 score system was validated to predict the clinical outcome of a patient.
Description: survival status as of February 24, 2020
Measure: survival status Time: 10 December 2019 to 10 February 2020The novel coronavirus (SARS-CoV-2) is a new strain of coronavirus found in human in 2019, which causes epidemic worldwide. Novel coronavirus disease (COVID-19) causes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in the severe and critically severe patients. Pulmonary edema is the key detrimental feature of ALI/ARDS. Autopsy of patients died from COVID-19 reported that, pulmonary mucus exudation was severe, more obvious than SARS infection. Pulmonary CT scanning and pathological findings also suggest that pulmonary edema caused by inflammatory exudation is a distinguished feature of COVID-19. However, specific pharmacotherapy is lacking.Vascular endothelial growth factor (VEGF) is known as the most potent inducing factors to increase vascular permeability. Bevacizumab is an anti VEGF recombinant humanized monoclonal antibody, which has been used in anti-tumor treatment for 16 years. Evidence suggest that Bevacizumab is a promising drug for severe and critical COVID-19 patients.
Description: The time from randomization to an improvement of two points on a seven-category ordinal scale or live discharge from the hospital
Measure: The time from randomization to clinical improvement Time: No more than 28 daysIn December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia caused by CoVID-19, and the number of cases of infection with CoVID-19 identified in Wuhan increased markedly over the later part of January 2020, with cases identified in multiple other Provinces of China and internationally.Given no specific antiviral therapy for CoVID-19 infection and the availability of Yinhu Qingwen Granula as a potential antiviral Chinese medicine based on vivo antiviral studies in CoVID-19, this adaptive, randomized,double-blind,controlled trial will evaluate the efficacy and safety of Yinhu Qingwen Granula in patients hospitalized with severe CoVID-19.
Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: clinical status rating on the 7-point ordinal scale Time: up to 30 daysDescription: TTCI is defined as the time (in days) from initiation of study treatment (Yinhu Qingwen Granula or its low-dose granula) until a decline of two categories from status at randomisation on the 7-point ordinal scale of clinical status which ranges from 0 (death) to 6 (Not hospitalized, no limitations on activities).
Measure: Time to Clinical Improvement (TTCI) Time: up to 30 daysDescription: Critical status is defined as: 1) respiratory failure with the need of invasive mechanical ventilation; or 2) shock; or 3) other system organ failure with ICU admission.
Measure: The incidence of critical status conversion in 30 days Time: up to 30 daysThis project aims to use artificial intelligence (image discrimination) algorithms, specifically convolutional neural networks (CNNs) for scanning chest radiographs in the emergency department (triage) in patients with suspected respiratory symptoms (fever, cough, myalgia) of coronavirus infection COVID 19. The objective is to create and validate a software solution that discriminates on the basis of the chest x-ray between Covid-19 pneumonitis and influenza
Description: Number of participants with pneumonitis on Chest X-Ray and COVID 19 positive
Measure: COVID-19 positive X-Rays Time: 6 monthsDescription: Number of participants with pneumonitis on Chest X-Ray and COVID 19 negative
Measure: COVID-19 negative X-Rays Time: 6 monthsComplete the examination of cardio-pulmonary ultrasound in accordance with the a-ccue process of patients with novel coronavirus bedside. To summarize and analyze the characteristics of cardiopulmonary ultrasound in patients with novel coronavirus pneumonia, and assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis. Auto line B is a method which is based on artificial intelligence is used to calculate the lungs ultrasonic B line numbers reviewing the status of patients with lung, and also evaluate patients' lungs using the traditional artificial semi-quantitative method, to evaluate those two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not, and verify consistency of ultrasonic evaluation method and the way of CT evaluation.
Description: Complete the examination of cardio-pulmonary ultrasound in accordance with the a-ccue process of patients with novel coronavirus bedside. To summarize and analyze the characteristics of cardiopulmonary ultrasound in patients with novel coronavirus pneumonia
Measure: characteristics of cardiopulmonary ultrasound Time: 30 minsDescription: assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis.
Measure: assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis. Time: 2-3weeksDescription: Auto line B is a method which is based on artificial intelligence is used to calculate the lungs ultrasonic B line numbers reviewing the status of patients with lung, and also evaluate patients' lungs using the traditional artificial semi-quantitative method, to evaluate those two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not
Measure: evaluate two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not, and verify consistency of ultrasonic evaluation method and the way of CT evaluation. Time: 3 hoursThis is phase II study to assess the efficacy of NestaCell® (mesenchymal stem cell) to treat severe COVID-19 pneumonia.
Description: Ordinal scale (WHO ordinal scale that measures illness severity over time)
Measure: Change in Clinical Condition Time: 10 daysDescription: Evaluation of Pneumonia change
Measure: Rate of mortality within 10-days Time: 10 daysDescription: Evaluation of Pneumonia change
Measure: Change of Clinical symptoms - respiratory rate Time: 10 daysDescription: oxygen saturation
Measure: Hypoxia Time: 10 daysDescription: oxygen saturation
Measure: PaO2 / FiO2 ratio Time: 10 daysDescription: Marker of Immunological function
Measure: CD4+ and CD8+ T cell count Time: Days 1, 2, 4, 6 and 8.Description: PaO2 / FiO2 ratio
Measure: Changes of blood oxygen Time: 10 daysDescription: Number of participants with treatment-related adverse events
Measure: Side effects in the treatment group Time: 10 daysDescription: Complete blood count, ALT, AST, GGT, CK, CKmB and creatinine
Measure: Complete blood count, cardiac, hepatic and renal profiles; Time: Days 1, 2, 4, 6 and 8.The emergence of SARS-CoV-2 is currently engaging and consuming most of resources of efficient healthcare systems in Europe, and several hospitals are currently experiencing a shortage of ICU beds for critically-ill patients with SARS-CoV-2 pneumonia. A risk stratification based on clinical, radiological and laboratory parameters seems necessary in order to better identify those patients who may need ICU admission and/or those who may benefit from a prompt antiviral therapy
Description: Composite of ICU admission or SpO2<92% with 100% FiO2 of oxygen treatment (reservoir mask or CPAP or NIV), respiratory rate >30 bpm, respiratory distress
Measure: Respiratory failure Time: 14 daysDescription: Incidence of bacterial superinfection among ventilated patients with SARS-CoV-2 pneumonia
Measure: Occurence of bacterial superinfection Time: 14 daysThis study project includes a single-arm phase 2 study and a parallel observational cohort study, enrolling patients with COVID-19 pneumonia.
Description: 1-month mortality is defined as the ratio of patients who will alive after 1month from study start out of those registered at baseline
Measure: One-month mortality rate Time: up to 1 monthDescription: IL-6 levels will be assessed using commercial ELISA method.
Measure: Interleukin-6 level Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 monthDescription: Lymphocyte count assessed by routinely used determination of blood count
Measure: Lymphocyte count Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 monthDescription: CRP is assessed by routinely used determination of CRP
Measure: CRP (C-reactive protein) level Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 monthDescription: calculated from arterial blood gas analyses (values from 300 to 100)
Measure: PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio) Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 monthDescription: It evaluates 6 variables, each representing an organ system (one for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems), and scored from 0 (normal) to 4 (high degree of dysfunction/failure). Thus, the maximum score may range from 0 to 24.
Measure: Change of the SOFA (Sequential Organ Failure Assessment) Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 monthDescription: graded according to CTCAE citeria (v5.0)
Measure: Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 Time: during treatment and up to 30 days after the last treatment doseDescription: Thoracic CT scan or Chest XR
Measure: Radiological response Time: at baseline (optional), after seven days and if clinically indicated (up to 1 month)Description: Days of hospitalization
Measure: Duration of hospitalization Time: from baseline up to patient's discharge (up to 1 month)Description: time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation
Measure: Remission of respiratory symptoms Time: up to 1 monthDescription: time to definitive extubation calculated from intubation (any time occurred) to extubation in days
Measure: Remission of respiratory symptoms Time: up to 1 monthDescription: time to independence from non-invasive mechanical ventilation calculated in days
Measure: Remission of respiratory symptoms Time: up to 1 monthDescription: time to independence from oxygen therapy in days
Measure: Remission of respiratory symptoms Time: up to 1 monthThis study is a multi-centered, three-armed, randomized, double-blinded, controlled study, namely, the oral trial drug favipiravir tablets plus chloroquine phosphatetablets tablets group (combined group), the oral trial drug favipiravir tablets group (pirovir group), and the oral placebo treatment group (control group). The total number of enrolled cases in this study was set at 150. During the treatment, the clinical data of the subjects were collected, the changes of viral load and biochemical indicators were detected, and the outcome of the subjects was monitored. The main indicators of efficacy include improvement or recovery of respiratory symptoms and viral nucleic acid shedding. The rate of progression to severe disease, duration of fever, peripheral blood index and improvement time of pulmonary imaging were the secondary indicators to evaluate the efficacy. Statistical analysis was performed at the middle and final stages of the study to evaluate the efficacy and safety of favipiravir tablets combined with chloroquine phosphatetablets tablets in the treatment of novel coronavirus pneumonia.
Description: Time of improvement or recovery of respiratory symptoms
Measure: Time of Improvement or recovery of respiratory symptoms Time: 10 days during the intervention periodDescription: Number of days from positive to negative for test of swab or sputum virus nucleic acid
Measure: Number of days virus nucleic acid shedding Time: 10 days during the intervention periodDescription: Frequency of improvement or recovery of respiratory symptoms
Measure: Frequency of Improvement or recovery of respiratory symptoms Time: 10 days during the intervention periodDescription: Duration of fever after recruitment
Measure: Duration of fever Time: 10 days during the intervention periodDescription: Disease is defined as severe if it meets any of the following criteria: 1.Respiratory rate ≥30/min; 2. Oxygen saturation ≤93%; 3. Arterial partial oxygen pressure (PaO2)/oxygen absorption concentration (FiO2) ≤300 mmHg (1 mmHg=0.133 kPa)
Measure: Frequencies of progression to severe illness Time: 10 days during the intervention periodDescription: Time of improvement of pulmonary imaging
Measure: Time of improvement of pulmonary imaging Time: 10 days during the intervention periodDescription: Peripheral blood c-reactive protein concentration
Measure: Peripheral blood c-reactive protein concentration Time: day-1,3,7,14 after the intervention periodDescription: Absolute value of peripheral blood lymphocytes
Measure: Absolute value of peripheral blood lymphocytes Time: day-1,3,7,14 after the intervention periodDescription: percentage of peripheral blood lymphocytes
Measure: percentage of peripheral blood lymphocytes Time: day-1,3,7,14 after the intervention periodThere is a high risk of transmission of COVID-19 to healthcare workers. In a recent cohort, 29% of the patients hospitalized were healthcare workers. Among the WHO's primary strategic objectives for the response to COVID-19, the first was to limit human-to-human transmission, including reducing secondary infections among close contacts and health care workers. Automated oxygen titration, weaning and monitoring (FreeO2 device) may be a solution to reduce the number of interventions of healthcare workers related to oxygen therapy, to reduce complications related to oxygen and to improve monitoring.
Description: The number of interventions required by healthcare workers to manage oxygen therapy (titration, weaning and monitoring) during 4 hours
Measure: The number of interventions Time: Hour0 to Hour4Description: The number of interventions required by healthcare workers to manage oxygen therapy (titration, weaning and monitoring) during 4 hours
Measure: Duration of interventions Time: Hour0 to Hour24Description: The Mean oxygen flow during study duration to evaluate oxygen consumption
Measure: Mean oxygen flow Time: Hour0 to Hour24 (1 day)Description: Time within SpO2 between 90 and 94%
Measure: Time within theSpO2 target Time: Hour0 to Hour24 (1 day)Description: Time within SpO2 < 88%
Measure: Time with hypoxemia Time: Hour0 to Hour24 (1 day)Description: Time within SpO2 > 96%
Measure: Time with hyperoxemia Time: Hour0 to Hour24 (1 day)Description: Rate of ICU admission
Measure: Rate of ICU admission Time: Hour0 to Hour24 (1 day)Description: Rate of needed non invasive respiratory support Non invasive ventilation or High Flow Nasal Therapy
Measure: Rate of needed non invasive respiratory support Time: Hour0 to Hour24 (1 day)Description: Rate of intubation
Measure: Rate of intubation Time: Hour0 to Hour24 (1 day)Description: Evaluation of NEWS 2 score evolution (National Early Warning score) correlate to patient evolution. The NEWS2 score will be calculate but no intervention will be made based on this score. Patient evolution will be compare at NEWS 2 interpretation. Interpretation A low score (NEWS 1-4) should prompt assessment by a competent registered nurse who should decide if a change to frequency of clinical monitoring or an escalation of clinical care is required. A medium score (ie NEWS of 5-6 or a RED score) should consider whether escalation of care to a team with critical-care skills is required (ie critical care outreach team). A high score (NEWS ≥7) should prompt emergency assessment by a clinical team/critical care outreach team with critical-care competencies and usually transfer of the patient to a higher dependency care area.
Measure: NEWS 2 score evolution Time: Hour0 to Hour24 (1 day)Description: Evaluation of EWSO2 score(Early Warning ScoreO2) evolution correlate to patient evolution The EWSO2 score will be calculate but no intervention will be made based on this score. Patient evolution will be compare at EWSO2 interpretation. Interpretation Favorable clinical outcome in patients with a score <5.3 A patient with a score >18.6 will experience a poor outcome.
Measure: EWSO2 score evolution Time: Hour0 to Hour24 (1 day)Description: Cost effectiveness ratio (cost per SpO2 unit)
Measure: Cost-effectiveness Time: From date of randomization until the date of hospital dischargeDescription: Duration of the hospital length of stay
Measure: length of stay Time: up to 90 days. Hospital stay - hospital admission through hospital discharge or until death if occuredThis study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of tocilizumab (TCZ) compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with severe COVID-19 pneumonia.
The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Around 20% of those infected have severe pneumonia and currently there is no specific or effective therapy to treat this disease. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. But those efforts have not involved large, carefully-conducted controlled studies that would provide the global medical community the proof that these drugs work on a significant scale. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with pneumonia by SARS-CoV2 virus.
Description: Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)
Measure: Evaluation of the clinical status Time: 15 days after randomizationDescription: All-cause mortality rates at 29 days after randomization
Measure: All-cause mortality Time: 29 days after randomizationDescription: Evaluation of the clinical status of patients on the 7th and 29th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)
Measure: Evaluation of the clinical status Time: 7 and 29 days after randomizationDescription: Number of days free from mechanical ventilation at 29 days after randomization
Measure: Number of days free from mechanical ventilation Time: 29 days after randomizationDescription: Number of days that the patient was on mechanical ventilation after randomization
Measure: Duration of mechanical ventilation Time: 29 days after randomizationDescription: Length of hospital stay on survivors
Measure: Duration of hospitalization Time: 29 days after randomizationDescription: Presence of other secondary infections
Measure: Other secondary infections Time: 29 days after randomizationDescription: Time from treatment start to death
Measure: Time from treatment start to death Time: 29 days after randomizationDescription: Morbimortality, daily life activities, mental health, and quality of life
Measure: Medium and long-term outcomes of SARS-CoV2 infection on morbimortality, daily life activities, mental health, and quality of life Time: 3, 6, 9 and 12 monthsDescription: Leucocyte transcriptome
Measure: Assess whether the tested therapies may be affected by leucocyte phenotype Time: BaselineDescription: Occurrence of QT interval prolongation
Measure: QT interval prolongation Time: 29 days after randomizationDescription: Occurrence of gastrointestinal intolerance
Measure: Gastrointestinal intolerance Time: 29 days after randomizationDescription: Occurrence of laboratory hematimetric parameters, creatinine and bilirubin
Measure: Laboratory abnormalities Time: 29 days after randomizationDescription: Occurrence of adverse events related to the use of the investigational products
Measure: Adverse events Time: 29 days after randomizationGrowing evidences are showing the usefulness of lung ultrasound in patients with COVID-19. Sars-CoV-2 has now spread in almost every country in the world. In this study, the investigators share their experience and propose a standardized approach in order to optimize the use of lung ultrasound in covid-19 patients. The investigators focus on equipment, procedure, classification and data-sharing.
Description: Scoring procedures Score 0: The pleura line is continuous, regular. Horizontal artifacts (A-line) are present. These artifacts are generally referred as A-lines. Score 1: The pleura line is indented. Below the indent, vertical areas of white are visible. Score 2: The pleura line is broken. Below the breaking point, small to large consolidated areas (darker areas) appear with associated areas of white below the consolidated area (white lung). Score 3: The scanned area shows dense and largely extended white lung with or without larger consolidations At the end of the procedure, the clinician will write for each area the highest score obtained.
Measure: Lung ultrasound grading system for COVID-19 pneumonia Time: At enrollment.Cytokines and chemokines are thought to play an important role in immunity and immunopathology during virus infections [3]. Patients with severe COVID-19 have higher serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8) compared to individuals with mild disease or healthy controls, similar to patients with SARS or MERS . The change of laboratory parameters, including elevated serum cytokine, chemokine levels, and increased NLR in infected patients are correlated with the severity of the disease and adverse outcome, suggesting a possible role for hyper-inflammatory responses in COVID-19 pathogenesis. Importantly, previous studies showed that viroporin E, a component of SARS-associated coronavirus (SARS-CoV), forms Ca2C-permeable ion channels and activates the NLRP3 inflammasome. In addition, another viroporin 3a was found to induce NLRP3 inflammasome activation . The mechanisms are unclear. Colchicine, an old drug used in auto-inflammatory disorders (i.e., Familiar Mediterranean Fever and Bechet disease) and in gout, counteracts the assembly of the NLRP3 inflammasome, thereby reducing the release of IL-1b and an array of other interleukins, including IL-6, that are formed in response to danger signals. Recently, colchicine has been successfully used in two cases of life-threatening post-transplant capillary leak syndrome. These patients had required mechanically ventilation for weeks and hemodialysis, before receiving colchicine, which abruptly restored normal respiratory function and diuresis over 48 hrs [4].
Description: Time to clinical improvement: defined as time from randomization to an improvement of two points from the status at randomization on a seven-category ordinary scale
Measure: Clinical improvement Time: Day 28Description: Live discharge from the hospital (whatever comes first)
Measure: Hospital discharge Time: Day 28Description: Number of death patients
Measure: Death Time: Day 28Description: 7-category ordinal scale
Measure: Clinical status Time: Day 7, Day 14Description: Number of patients with mechanical ventilhation
Measure: Mechanical ventilhation Time: Day 28Description: Days of hospitalization
Measure: Hospitalization Time: Day 28Description: Days to death from treatment initiation
Measure: Time from treatment initiation to death Time: Day 28Description: negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart
Measure: Time to Negativization COVID 19 Time: Day 21Description: Time to remission of fever in patients with T>37.5°C at enrollment
Measure: Fever Time: Day 1,4,7,14,21,28Different studies showed that ascorbic acid (vitaminC) positively affects the development and maturation of T-lymphocytes, in particular NK (natural Killer) cells involved in the immune response to viral agents. It also contributes to the inhibition of ROS production and to the remodulation of the cytokine network typical of systemic inflammatory syndrome. Recent studies have also demonstrated the effectiveness of vitamin C administration in terms of reducing mortality, in patients with sepsis hospitalized in intensive care wards. Given this background, in the light of the current COVID-19 emergency, since the investigators cannot carry out a randomized controlled trial, it is their intention to conduct a study in the cohort of hospitalized patients with covid-19 pneumonia, administering 10 gr of vitamin C intravenously in addition to conventional therapy.
Description: Change of hospital mortality
Measure: In-hospital mortality Time: 72 hoursDescription: Reduction of PCR levels > 50% in comparison with PCR levels at the admission, within 72 hours after the administration
Measure: PCR levels Time: 72 hoursDescription: Change of the lactate clearance
Measure: Lactate clearance Time: 72 hoursDescription: Change of hospital stay days
Measure: Hospital stay Time: 72 hoursDescription: Resolution of symptoms (Fever, Cough, Shortness of breath or difficulty breathing)
Measure: Symptoms Time: 72 hoursDescription: Change of duration of positive swab (nasopharynx and throat)
Measure: Positive swab Time: 72 hoursDescription: Resolution of tomography imaging (example, patches located in the subpleural regions of the lung)
Measure: Tomography imaging Time: 72 hoursIn December 2019, the Municipal Health Committee of Wuhan, China, identified an outbreak of viral pneumonia of unknown cause. This new coronavirus was called SARS-CoV-2 and the disease caused by that virus, COVID-19. Recent numbers show that 222,643 infections have been diagnosed with 9115 deaths, worldwide. Currently, there are no approved therapeutic agents available for coronaviruses. In this scenario, the situation of a global public health emergency and evidence about the potential positive effect of chloroquine (CQ) in most coronaviruses, including SARS-CoV-1, and recent data on small trials on SARS-CoV-2, the investigators intend to investigate the efficacy and the safety of CQ diphosphate in the treatment of hospitalized patients with severe acute respiratory syndrome in the scenario of SARS-CoV2. Preliminary in vitro studies and uncontrolled trials with low number of patients of CQ repositioning in the treatment of COVID-19 have been encouraging. The main hypothesis is that CQ diphosphate will reduce mortality in 50% in those with severe acute respiratory syndrome infected by the SARS-COV2. Therefore, the main objective is to assess whether the use of chloroquine diphosphate reduces mortality by 50% in the study population. The primary outcome is mortality in day 28 of follow-up. According to local contingency plan, developed by local government for COVID-19 in the State of Amazonas, the Hospital Pronto-Socorro Delphina Aziz, located in Manaus, is the reference unit for the admission of serious cases of the new virus. The unit currently has 50 ICU beds, with the possibility of expanding to 335 beds, if needed. The hospital also has trained multiprofessional human resources and adequate infrastructure. In total, 440 participants (220 per arm) will receive either high dose chloroquine 600 mg bid regime (4x150 mg tablets, every 12 hours, D1-D10) or low dose chloroquine 450mg bid regime (3x150mg tablets + 1 placebo tablet every 12 hours on D1, 3x150mg tablets + 1 placebo followed by 4 placebo tablets 12h later from D2 to D5, and 4 placebo tablets every 12 hours, D6-D10). Placebo tablets were used to standardize treatment duration and blind research team and patients. All drugs administered orally (or via nasogastric tube in case of orotracheal intubation). Both intervention and placebo drugs will be produced by Farmanguinhos. Clinical and laboratory data during hospitalization will be used to assess efficacy and safety outcomes.
Description: proportion of deaths at day 28 between groups compared
Measure: Mortality rate reduction of 50% by day 28 Time: 28 days after randomizationDescription: number of deaths at days 7 and 14 between groups compared
Measure: Absolute mortality on days 7 and 14 Time: 7 and 14 days after first doseDescription: clinical status
Measure: Improvement in overall subject's clinical status assessed in standardized clinical questionnaires on days 14 and 28 Time: 14 and 28 days after first doseDescription: clinical status
Measure: Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization Time: during and after intervention, up to 28 daysDescription: supplemental oxygen
Measure: Duration of supplemental oxygen (if applicable) Time: during and after intervention, up to 28 daysDescription: mechanical ventilation
Measure: Duration of mechanical ventilation (if applicable) Time: during and after intervention, up to 28 daysDescription: hospitalization
Measure: Absolute duration of hospital stay in days Time: during and after intervention, up to 28 daysDescription: adverse events grade 3 and 4
Measure: Prevalence of grade 3 and 4 adverse events Time: during and after intervention, up to 28 daysDescription: adverse events
Measure: Prevalence of serious adverse events Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum creatinine compared to baseline
Measure: Change in serum creatinine level Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum troponin I compared to baseline
Measure: Change in serum troponin I level Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum aspartate aminotransferase compared to baseline
Measure: Change in serum aspartate aminotransferase level Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum aspartate aminotransferase compared to baseline
Measure: Change in serum CK-MB level Time: during and after intervention, up to 28 daysDescription: virus clearance from respiratory tract secretion
Measure: Change in detectable viral load in respiratory tract swabs Time: during and after intervention, up to 28 daysDescription: viremia in blood detected through RT-PCR
Measure: Viral concentration in blood samples Time: during and after intervention, up to 28 daysDescription: death
Measure: Absolute number of causes leading to participant death (if applicable) Time: during and after intervention, up to 28 daysCOVID-19 infection is overwhelming Italian healthcare. There is an urgent need for a solution to the lack of ICU beds and increasing deaths day after day. A recent retrospective Chinese paper (JAMA Intern Med, online March 13, 2020) showed impressive positive effect of methylprednisolone (MP) on survival of SARS-CoV-2 critically ill patients. Moreover, the Italian Infectious Disease leading institution guidelines for COVID-19 clinical management included as an option for patients with "incipient worsening of respiratory functions" methylprednisolone treatment at an approximate dose of 80mg. The main objective of this multi-centre observational trial is to analyse the association of low dose prolonged infusion of methylprednisolone (MP) for patients with severe acute respiratory syndrome with composite primary end-point (ICU referral, need for intubation, in-hospital death at day 28).
Description: We reported below the number of participants meeting at least one of three among death or ICU admission or Invasive mechanical ventilation.
Measure: Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28 Time: 28 daysDescription: We reported below the number of participants who died within 28 days, during the hospital stay.
Measure: In-hospital Death Within 28 Days Time: 28 daysDescription: We reported below the number of participants admitted to ICU within 28 days.
Measure: Admission to Intensive Care Unit (ICU) Time: 28 daysDescription: We reported below the number of participants who needed endotracheal intubation during ICU admission
Measure: Endotracheal Intubation (Invasive Mechanical Ventilation) Time: 28 daysDescription: Change in C-reactive protein after 7 days from baseline. A reduction of CRP reveals a laboratory improvement.
Measure: Change in C-reactive Protein (CRP) Time: 7 daysDescription: number of days free from mechanical ventilation (both invasive and non-invasive) by day 28
Measure: Change in Duration of Mechanical Ventilation Time: 28 daysIn December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. Our primary goal is to investigate the efficacy of treatment with a CytoSorb® adsorber in patients with severe COVID-19 disease requiring venous ECMO over 72 hours after initiation of ECMO. The primary endpoint is the reduction of plasma interleukin-6 levels 72 hours after initiation of ECMO support. As secondary endpoints we investigate 30-day survival, vasopressor and volume requirements, lactate in terms of lactate and platelet function. As safety variables, we further investigate the levels of the applied antibiotics (usually ampicillin and sulbactam).
Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)
Measure: interleukin-6 (IL-6) level after 72 hours Time: 72 hoursDescription: survival after 30 days
Measure: 30-day-survival Time: 72 hoursDescription: needed dosage of norepinephrine and other vasopressors
Measure: vasopressor dosage Time: 72 hoursDescription: fluid balance levels during cytokine adsorption
Measure: fluid balance Time: 72 hoursDescription: serum-lactate levels during cytokine adsorption
Measure: lactate Time: 72 hoursIt has been reported that nearly half of the patients who are hospitalized for Covid-19 pneumonia have on admission old age or comorbidities. In particular, hypertension was present in 30% of the cases, diabetes in 19%, coronary heart disease in 8% and chronic obstructive lung disease in 3% of the patients. Amazingly, in the two major studies published in the Lancet (Zhou F et al Lancet 2020) and in the New England Journal of Medicine (Guan W et al 2020), the weight of the subjects as well their body mass index (BMI) were omitted. However, obesity, alone or in association with diabetes, can be a major predisposition factor for Covid-19 infection. The primary end-point of our prospective, observational study is to assess the recovery rate in patients with diagnosis of Covid-19 pneumonia. Among the other secondary end-points, we intend to find the predictors of the time to clinical improvement or hospital discharge in patients affected by Covid-19 pneumonia.
Description: mean rate of recovery in patients with diagnosis of Covid-19 pneumonia, who present with complications at the time of hospital admission (such as diabetes, obesity, cardiovascular disease, hypertension or respiratory failure), with the mean recovery rate in patients without any of the above-mentioned complications.
Measure: rate of recovery Time: 3 weeksDescription: comparison of the survival curves (times to improvement) in the two groups (patients with and without complications) and among patients presenting with different types of complications
Measure: time to improvement Time: 3 weeksDescription: the efficacy of different pharmaceutical treatment against Covid-19
Measure: efficacy of treatments Time: 3 weeksDescription: liver, kidney or multiorgan failure, cardiac failure
Measure: organ failure Time: 3 weeksHealthcare professionals mainly doctors, nurses and their first degree relatives (spouse, father, mother, sister, brother, child) who have been started hydroxychloroquine(plaquenil) 200mg single dose repeated every three weeks plus vitaminC including zinc once a day were included in the study. Study has conducted on 20th of march. Main purpose of the study was to cover participants those who are facing or treating COVID19 infected patients in Ankara.
Description: persons who took this medication should not have an infection
Measure: Protection against COVID-19 Time: 4 monthsCoronavirus 2019 (COVID-19) is a respiratory tropism virus transmitted through droplets emitted into the environment of infected persons. The symptoms can be extremely varied and the course can range from spontaneous healing without sequelae to death. Currently, the diagnosis of certainty for resuscitation patients (by definition "severe") is based on searching for a fragment of virus genetic material within the epithelial cells of the respiratory tree, up and/or down, by PCR. It is to be expected that the epidemic peak will make it difficult (if not impossible) to respect the stereotypical path that is currently in place, due to the lack of space in the specific unit. This will require optimization of care pathways and use of the specific sectors. It is therefore necessary to define the simple criteria, available from the moment patients are admitted, to predict the result of the COVID-19 PCR.
Description: Assessment of viral, bacterial, fungal and parasitic rate in confirmed and unconfirmed patients for COVID-19
Measure: Coinfections Time: during ICU stay, up to 28 daysDescription: it will be reported the evolution of respiratory dysfunction in patients infected with COVID-19 admitted to ICU during their stay and requiring mechanical ventilation (during, Pao2/FIO2 ratio,,features of artificial ventilation features of extra-bodied respiratory assistance)
Measure: Respiratory dysfunction requiring mechanical ventilation Time: during ICU stay, up to 28 daysDescription: the SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure).
Measure: Sequential Organ Failure Assessment (SOFA) Score Time: during ICU stay, up to 28 daysDescription: APS II was designed to measure the severity of disease for patients admitted to Intensive care units 24 hours after admission to the ICU, the measurement has been completed and resulted in an integer point score between 0 and 163 and a predicted mortality between 0% and 100%.
Measure: SAPS II score Time: at admissionDescription: The DIC Score was developed by the The International Society of Thrombosis and Haemostasis (ISTH.) The DIC score calculator accounts of the following four parameters.Each of the four parameters evaluated above have values that are weighted with a number of points varying from 0 to 3. By summing the points given to the choices, a final result between 0 and 8 is obtained
Measure: Disseminated Intravascular Coagulation (DIC) score Time: during ICU stay, up to 28 daysDescription: measuring the long-term impact of confirmed COVID-19 infection. assessment of quality of life according to 8 areas: physical activity (and related limitations), body pain, perception of one's own health, mental health (and related limitations), social life and vitality.
Measure: Short Form 36 Time: at 9 months +/- 3 months after ICU stayDescription: The scale allows to detect anxiety and depression using 14 items rated from 0-3. Measuring the long-term impact of confirmed COVID-19 infection
Measure: Hospital anxiety and depression scale (HADS) Time: at 9 months +/- 3 months after ICU stayDescription: 22-item self-report measure that assesses subjective distress caused by traumatic events Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88) Measuring the long-term impact of confirmed COVID-19 infection
Measure: Impact of Event Scale - revised (IES-R) Time: at 9 months +/- 3 months after ICU stayDescription: Question the stressful experience or event, followed by 20 multiple-choice questions. Measuring the long-term impact of confirmed COVID-19 infection
Measure: Post-traumatic stress disorder Checklist version DSM-5 (PSL-5) Time: at 9 months +/- 3 months after ICU stayDescription: The mMRC Dyspnea Scale stratifies severity of dyspnea in respiratory diseases Measuring the long-term impact of confirmed COVID-19 infection
Measure: Modified Medical Research Council (MMRC) Dyspnea Scale Time: at 9 months +/- 3 months after ICU stayDescription: Evolution of viral clearance in nasal and depp PCR during ICU
Measure: Viral clearance Time: through study completion, an average of 28 daysOn Dec 31, 2019, a number of viral pneumonia cases were reported in China. The virus causing pneumonia was then identified as a new coronavirus called SARS-CoV-2. Since this time, the infection called coronavirus disease 2019 (COVID-19) has spread around the world, causing huge stress for health care systems. To diagnose this infection, throat and nose swabs are taken. Unfortunately, the results often take more than 24 hrs to return from a laboratory. Speeding diagnosis up would be of great help. This study aims to look at the breath to find signs that might allow clinicians to diagnose the coronavirus infection at the bedside, without needing to send samples to the laboratory. To do this, the team will be using a machine called a BreathSpec which has been adapted to fit in the hospital for this purpose.
Description: breath sample collection
Measure: To perform a study in patients with clinical features of pneumonia/chest infection to identify a signature of Covid-19 pneumonia in patients exposed to SARS-CoV-2, compared to unexposed patients or those without. Time: up to daily during hospital admissionDescription: breath sample collection
Measure: Detection of markers of Covid-19 pneumonia in non-invasive breath samples. Time: daily until the patient has ben discharged from hospital or it is deemed inappropriate to continueDescription: breath sample collection
Measure: Relationship of this biomarker signature to the presence of SARS-CoV-2 in nasal and throat swabs. Time: daily until the patient has ben discharged from hospital or it is deemed inappropriate to continueDescription: breath sample collection
Measure: Subsequently, the signature's relationship to other biomarkers of SARS-CoV-2 infection which are currently being explored Time: daily until the patient has ben discharged from hospital or it is deemed inappropriate to continueDescription: breath sample collection
Measure: In a smaller group of participants, ideally daily non-invasive breath samples will be collected to determine if there are changes between SARS-CoV-2 positive patients and those that are negative until hospital discharge or undue participant burden . Time: daily until the patient has ben discharged from hospital or it is deemed inappropriate to continueIn our center up to 25% of the hospitalized patients with COVID-19 progress and need an intensive care unit. It is urgent to find measures that can avoid this progression to severe stages of the disease. We hypothesize that the use of anti-inflammatory drugs used at the time they start hyperinflammation episodes could improve symptoms and prognosis of patients and prevent their progression sufficiently to avoid their need for be admitted to an Intensive Care Unit.
Rationale: The clinical manifestations of SARS-CoV-2 infection in children are poorly characterized. Preliminary findings indicate that they may be atypical. There is a need to identify the spectrum of clinical presentations, predictors of severe disease (COVID-19) outcomes, and successful treatment strategies in this population. Goals: Primary - Describe and compare characteristics of confirmed SARS-CoV-2 infected children with symptomatic test-negative children. Secondary - 1) Describe and compare confirmed SARS-CoV-2 infected children with mild versus severe COVID-19 outcomes; 2) Describe healthcare resource utilization for, and outcomes of, screening and care of pediatric COVID-19 internationally, alongside regional public health policy changes. Methods: This prospective observational study will occur in 50 emergency departments across 11 countries. We will enroll 12,500 children who meet institutional screening guidelines and undergo SARS-CoV-2 testing. Data collection focuses on epidemiological risk factors, demographics, signs, symptoms, interventions, laboratory testing, imaging, and outcomes. Collection will occur at enrollment, 14 days, and 90 days. Timeline: Recruitment will last for 12 months (worst-case model) and will begin within 7-14 days of funding notification after ongoing expedited review of ethics and data sharing agreements. Impact: Results will be shared in real-time with key policymakers, enabling rapid evidence-based adaptations to pediatric case screening and management.
Description: Clinical characteristics among children presenting to a participating hospital's EDs who meet each site's local SARS-CoV-2 screening criteria, will be described and compared between children with confirmed SARS-CoV-2 (i.e. test-positive) versus suspected (i.e. test-negative) infections.
Measure: Clinical characteristics of children with SARS-CoV-2 Time: 18 monthsDescription: Factors associated with severe outcomes [i.e. positive pressure ventilation (invasive or noninvasive) OR intensive care unit admission with ventilatory or inotropic support OR death; other outcomes may be added as the understanding of the epidemic evolves) will be identified in confirmed paediatric COVID-19 cases.
Measure: Factors associated with severe COVID-19 outcomes Time: 18 monthsDescription: Health care resource utilization for patient management (e.g. frequencies of isolation, laboratory testing, imaging, and supportive care, with associated costs) of both suspected and confirmed SARS-CoV-2 infected children according to changes in national and regional policies.
Measure: Health care resource utilization for COVID-19 patient management Time: 18 monthsDescription: The sensitivity and specificity of various case screening policies for the detection of confirmed symptomatic SARS-CoV-2 infection (i.e. COVID-19) in children (e.g. addition of vomiting/diarrhoea).
Measure: Sensitivity and specificity of COVID-19 case screening policies Time: 18 monthsA phase1/2, open label, dose escalation, safety and early efficacy study of CAStem for the treatment of severe COVID-19 associated with or without ARDS.
Description: Frequency of adverse reaction (AE) and severe adverse reaction (SAE) within 28 days after treatment
Measure: Adverse reaction (AE) and severe adverse reaction (SAE) Time: Within 28 days after treatmentDescription: Evaluation by chest CT
Measure: Changes of lung imaging examinations Time: Within 28 days after treatmentDescription: Marker for SARS-CoV-2
Measure: Time to SARS-CoV-2 RT-PCR negative Time: Within 28 days after treatmentDescription: The duration of a fever above 37.3 degrees Celsius
Measure: Duration of fever (Celsius) Time: Within 28 days after treatmentDescription: Marker for efficacy
Measure: Changes of blood oxygen (%) Time: Within 28 days after treatmentDescription: Marker for efficacy
Measure: Rate of all-cause mortality within 28 days Time: Within 28 days after treatmentDescription: Counts of lymphocyte in a litre (L) of blood
Measure: Lymphocyte count (*10^9/L) Time: Within 28 days after treatmentDescription: Alanine aminotransferase in unit (U)/litre(L)
Measure: Alanine aminotransferase (U/L) Time: Within 28 days after treatmentDescription: Creatinine in micromole (umol)/litre(L)
Measure: Creatinine (umol/L) Time: Within 28 days after treatmentDescription: Creatine kinase in U/L
Measure: Creatine kinase (U/L) Time: Within 28 days after treatmentDescription: C-reactive in microgram (mg)/litre(L)
Measure: C-reactive protein (mg/L) Time: Within 28 days after treatmentDescription: Procalcitonin in nanogram (ng)/litre(L)
Measure: Procalcitonin (ng/L) Time: Within 28 days after treatmentDescription: Lactate in millimole(mmol)/litre(L)
Measure: Lactate (mmol/L) Time: Within 28 days after treatmentDescription: IL-1beta in picogram(pg)/millilitre(mL)
Measure: IL-1beta (pg/mL) Time: Within 28 days after treatmentDescription: IL-2 in pg/mL
Measure: IL-2 (pg/mL) Time: Within 28 days after treatmentDescription: IL-6 in pg/mL
Measure: IL-6 (pg/mL) Time: Within 28 days after treatmentDescription: IL-8 in pg/mL
Measure: IL-8 (pg/mL) Time: Within 28 days after treatmentCoronavirus disease-2019 (COVID-19) has a quoted inpatient mortality as high as 25%. This high mortality may be driven by hyperinflammation resembling cytokine release syndrome (CRS), offering the hope that therapies targeting the interleukin-6 (IL-6) axis therapies commonly used to treat CRS can be used to reduce COVID-19 mortality. Retrospective analysis of severe to critical COVID-19 patients receiving tocilizumab demonstrated that the majority of patients had rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose. Hypotheses: 1. Tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death. 2. Low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with and without clinical risk factors for clinical decompensation, intensive care utilization, and death. Objectives: 1. To establish proof of concept that tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize. 2. To establish proof of concept that low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients without clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.
Description: Tmax Response: Resolution of fever (from Tmax > 38C in 24H period to Tmax < 38C in following 24H period, with Tmax measured by commonly accepted clinical methods [forehead, tympanic, oral, axillary, rectal]). Maximum temperature within 24-hour period of time (0:00-23:59) on the day prior to, day of, and every 24 hours after tocilizumab administration. The primary endpoint is absence of Tmax greater than or equal to 38ºC in the 24-hour period following tocilizumab administration.
Measure: Clinical response Time: Assessed for the 24 hour period after tocilizumab administrationDescription: CRP normalization rate: Calculated as the ratio of the number of patients who achieve normal CRP value following tocilizumab administration and total number of patients who receive tocilizumab. Time to CRP normalization: Calculated as the number of hours between tocilizumab administration and first normal CRP value.
Measure: Biochemical response Time: Assessed every 24 hours during patient's hospitalization, up to 4 weeks after tocilizumab administrationDescription: 28-Day Overall Survival is defined as the status of the patient at the end of 28 days, beginning from the time of the first dose of tocilizumab.
Measure: Overall survival Time: 28 daysDescription: This will be defined as the percentage of patients who are discharged in stable condition compared to the percentage of patients who die in the hospital. Patients who are discharged to hospice will be excluded from this calculation.
Measure: Survival to hospital discharge Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a binary outcome defined by worsening COVID-19 pneumonitis resulting in transition from clinical Group A or Group B COVID-19 pneumonitis to critical COVID-19 pneumonitis during the course of the patient's COVID-19 infection. This diagnosis will be determined by treating physicians on the basis of worsening pulmonary infiltrates on chest imaging as well as clinical deterioration marked by persistent fever, rising supplemental oxygen requirement, declining PaO2/FiO2 ratio, and the need for intensive care such as mechanical ventilation or vasopressor/inotrope medication(s).
Measure: Progression of COVID-19 pneumonitis Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of non-invasive (BiPap, heated high-flow nasal cannula) or invasive positive pressure ventilation during the course of the patient's COVID-19 infection. For patients admitted to the hospital using non-invasive mechanical ventilation, the utilization of mechanical ventilation will count toward this metric, as well. Calculated as the ratio of the number of patients who require non-invasive or invasive positive pressure ventilation during hospitalization and total number of patients who receive tocilizumab.
Measure: Rate of non-elective mechanical ventilation Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between initiation and cessation of mechanical ventilation (invasive and non-invasive).
Measure: Duration of mechanical ventilation Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between tocilizumab dose administration and the initiation of mechanical ventilation. This will be treated as a time-to-event with possible censoring.
Measure: Time to mechanical ventilation Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a binary outcome defined as utilization of any vasopressor or inotropic medication during the course of the patient's COVID-19 infection. Calculated as the ratio of the number of patients who require vasopressor or inotrope medication during hospitalization and total number of patients who receive tocilizumab.
Measure: Rate of vasopressor/inotrope utilization Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor or inotrope medication(s).
Measure: Duration of vasopressor/inotrope utilization Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between first tocilizumab dose administration and the initiation of vasopressor or inotropic medication(s). This will be treated as a time-to-event with possible censoring.
Measure: Time to vasopressor or inotropic utilization Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administrationDescription: Number of ICU days is defined as the time period when a patient is admitted to the ICU (defined as the timestamp on the first vital signs collected in an ICU) until they are transferred from the ICU to a non-ICU setting such as a general acute care bed (defined as the timestamp on the first vital signs collected outside an ICU, excepting any "off the floor" vital signs charted from operating rooms or procedure or imaging suites). Death in the ICU will be a competing risk.
Measure: Number of ICU days Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: Duration of increased supplemental oxygen requirement from baseline is defined as the time period (number of days) during which the participant requires supplemental oxygen in excess of his/her baseline supplemental oxygen requirement. The supplemental oxygen requirement is defined as the highest liters-per-minute flow of supplemental oxygen required by the patient each day over the course of the hospitalization.
Measure: Duration of Increased Supplemental Oxygen Requirement from Baseline Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administrationThe current spread of the COrona VIrus Disease-2019 (COVID-19) epidemic in Italy, and the current lack of effective and approved drugs for its treatment, poses the problem of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients management, especially those who underwent to experience COVID-19 complications, such as CRS. This unmet need becomes more severe if the investigator consider that, the COVID-19 mortality stands around 2% in the general population, but it rises to 49% when considering intensive care unit (ICU) patients. To increase the chances of survival of these patients, the compassionate use of the available drugs is required, based on literature data, to the best of our abilities. ICU patients with cytokine release syndrome (CRS) secondary to COVID-19, show increased production of pro-inflammatory cytokines, including interleukin (IL-6), IL-2, IL-7, IL-10, tumor necrosis factor (TNF)-α and interferon (INF)γ, similar to that found in patients who develop CRS secondary to Chimeric Antigen Receptor-T (CAR-T) therapy. Although immuno-modulatory therapy is not routinely recommended in COVID-19 pneumonia, tocilizumab might have a rationale in those patients who develop CRS, blocking the complications caused by high levels of IL-6, and possibly preventing the development of a multi-organ failure. Reassuring data in this sense, come from the first studies conducted in China. In a Chinese pilot study, Xiaoling Xu and collaborators used tocilizumab (at a dosage of 400 mg iv in a single dose, with a possible second dose in case of no clinical response) in patients with COVID-19 in the presence of one of the following criteria: i) respiratory rate ≥ 30 acts/min; ii) SpO2 ≤ 93% in ambient air; iii) PaO2/FiO2 ≤ 300 mmHg. In the 21 patients treated with tocilizumab a significant reduction in IL-6 levels and fever, with improvement in lung function, was demonstrated. Besides, 90% of treated patients showed an improvement in the radiological picture, in terms of a decrease in the frosted glass areas, and a return to normal lymphocytes count in the peripheral blood. This is a prospective observational clinical study and it is aimed at verifying tocilizumab efficacy and safety in patients with COVID-19 complicated by acute distress respiratory syndrome (ARDS) and CRS.
Description: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours; SpO2 normalization criterion: SpO2> 94% for at least 72 hours
Measure: Percentage of patients with complete recovery defined as fever disappearance and return to normal peripheral oxygen saturation values (SpO2) after 14 days from the end of treatment with tocilizumab. Time: 14 daysDescription: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours
Measure: Percentage of patients with partial recovery defined as the disappearance of fever 14 days after the end of treatment with tocilizumab. Time: 14 daysDescription: days
Measure: Duration of hospitalization Time: 14 daysDescription: days
Measure: Time to the first negative SARS-CoV-2 negative RT-PCR test Time: 14 daysDescription: number/microliter
Measure: Changes from the baseline in the white blood cell count Time: 7, 14 daysDescription: number/microliter
Measure: Changes from the baseline in the lymphocyte populations (cluster of differentiation (CD)3+CD4+, CD3+CD8+, CD19+, Th17) Time: 7, 14 daysDescription: (ST segments elevation or depression, T-wave changes)
Measure: Changes in myocardial ischemia signs at the electrocardiographic trace (YES or NO) Time: 7,14 daysCurrently there are no proven treatment option for COVID-19. Human convalescent plasma is an option for COVID-19 treatment and could be available from people who have recovered and can donate plasma.
Description: reduction in oxygen and ventilation support
Measure: reduction in oxygen and ventilation support Time: through study completion, an average of 4 weeksThe novel coronavirus SARS-CoV-2 (COVID-19) is an emerging respiratory virus that causes pneumonia. WHO data reported admission to the intensive care unit (ICU) for 6% of patients, with a mortality rate reaching 45%. To date, apart from therapeutic trials, ICU management is symptomatic, based on organ failure support therapies. In the initial phase, the therapeutic management also includes empiric antimicrobial therapy (90% of patients, in accordance with LRTI guidelines (ATS 2019) and SRLF Guidelines (2020). One challenge for the ICU physicians is the timing for discontinuation of antimicrobial treatment, especially in case of shock or ARDS, considering that a substantial proportion of COVID-19 pneumonia patients may have pulmonary bacterial coinfection/superinfection. In order to avoid unnecessary prolonged antimicrobial therapy, and subsequent selective pressure, two tests could be combined in a personalized antibiotic strategy: - Procalcitonin (PCT): PCT is a useful tool to guide antibiotics discontinuation in community-acquired pneumonia) and viral pneumonia (PMID24612487). - Respiratory multiplex PCR FA-PPP (Biomérieux®): panel has been enlarged, including 8 viruses and 18 bacteria (quantitative analysis). The turnaround time is short. Sensitivity is high (99%, PMID32179139). It may contribute, in combination with conventional tests, to accelerate and improve the microbiological diagnosis during severe COVID-19 pneumonia. The hypothesize of the study is that the combination of the mPCR FA-PPP and PCT could be used to reduce antibiotics exposure in patients with severe confirmed COVID-19 pneumonia, with a higher clinical efficacy and safety as compared with a conventional strategy.
Description: the number of days alive without any antibiotics at Day 28. The D28 time point is usual in studies assessing antibiotics saving in ICU patients.
Measure: Number of antibiotic free days Time: Day 28Description: Total exposure to antibiotics
Measure: Antibiotics duration at D28 Time: Day 28Description: using a quality of life questionnaire (EQ5D5L)
Measure: Quality of life Quality of life Time: Day 90The recent pandemic due to the SARS-CoV2 results in a pulmonary infection in major symptomatic patients. Because of the large number of patients and the risk of acute respiratory distress syndrome (which seems to occur in almost 5% of patients), there is a real challenge to improve physician ability to screen between patients those who will require specific surveillance and those who can be sent back home. The recent French official recommendation of the French radiology society prescribe that chest X-ray do not have any place in the COVID-19+ management whereas the WHO stipulate that ultrasound machines may be useful for these patients [1-2]. Moreover, scattered recent publications tend to stress the interest of quick ultrasound imaging for COVID-19 suspected patients for screening purpose [2-5]. The aim of this observational historico-prospective study is to assess the risk of severe clinical outcomes (admission in continuous care unit (USC), invasive respiratory assistance, death) in patients suspected or diagnosed COVID-19+ as a function of initial pulmonary ultrasound abnormalities. These clinical outcomes are assessed through phone calls at D5, D15, M1. The secondary objectives are: - Assessing the concordance between the severity of pulmonary lesions as detected by pulmonary ultrasound devices and the ones detected by CT-scanner, for patients who will undergo these two examinations. - Assessing the compared performances in detecting ultrasound pulmonary lesions for patients suspected or diagnosed COVID-19+, between an experimented operator and a newly trained operator.
Description: Association of pulmonary lesions on ultrasound on D0 classified according to three stages of severity There are few B lines at the lung bases Bi-lateralization of B lines, numerous diffuse and / or curtain sign Presence of signs of pulmonary consolidation, hepatization of the lung and air bronchogram)
Measure: Association of pulmonary lesions on ultrasound on D0 classified according to three stages of severity Time: at day0Phase II, prospective, interventional, single-arm, multicentric, open label trial, with a parallel retrospective collection of data on not treated patients from IRCCS, San Raffaele Scientific Institute included in the institutional observational study. A sample of 50 patients with COVID-19 pneumonia will allow to detect an absolute reduction in the rate of Respiratory-failure at day+14 after treatment of 20%, assuming that the actual rate of failure in the corresponding not treated patients is 70% (alpha=5%, power=90%, two-sided test). The software PASS15 was used for calculations. The study will also include a parallel retrospective group of temporally concomitant patients from IRCCS, San Raffaele Scientific Institute, who did not receive an experimental treatment and who are enrolled in an already IRB approved observational study
Description: To demonstrate that the treatment with Defibrotide administered intravenously in addition to the best available therapy according to institutional guidelines (protease inhibitors antiviral treatment and hydroxychloroquine (HCQ), and if needed, metilprednisolone is able to reduce the progression of acute respiratory failure, the need of mechanical ventilation, the transfer to the intensive care unit or death, in patients with severe COVID-19 pneumonia. Patients with a baseline PaO2/FiO2 >= 200: progression of respiratory failure is defined by: severe gas transfer deficit (PaO2/FiO2 < 200); persistent respiratory distress while receiving oxygen (persistent marked dyspnea, use of accessory respiratory muscles, paradoxical respiratory movements); transfer to the intensive care unit; death. The rate will be calculated as the proportion of patients who experienced at least one of the events above by day+14 from treatment start.
Measure: to able to reduce the progression of acute respiratory failure Time: 14 daysDescription: To evaluate the safety of Defibrotide will be analyzed the frequency and incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Measure: Adverse events Time: 7 daysDescription: evaluate the time of hospitalization that will determine how much and how the administration of defibrotide can resolve the infection
Measure: duration of hospitalization Time: 14 daysDescription: To evaluate the level of PCR, LDH, ferritin, IL-10, IL-6, TNF-alpha, IFN-gamma, PTX3 at day +7 and +14 after start of treatment with Defibrotide. performed per day. Laboratory values performed at day 7 and 14 will be analyzed and compared with each other to understand their progress.
Measure: systemic inflammation Time: 14 daysDescription: To evaluate the overall survival at day+28 after start treatment with Defibrotide
Measure: overall survival Time: 28 daysThis is a prospective, multicenter, randomized, controlled, open-label, phase 2 clinical trial
Description: Assessed by hospital records
Measure: Percentage of patients with normalization of oxygen saturation by pulse oximetry (SpO2) ≥96% Time: through day 14 after study treatment initiationDescription: Assessed by hospital records
Measure: Proportion of patients with temperature < 37,5 °C armpit. Time: through day 14 after study treatment initiationDescription: Assessed by hospital records
Measure: Proportion of patients discharged from the emergency department and classified as low risk Time: In less than 28 daysDescription: The clinical status will be assessed by the SOFA scores
Measure: Change from baseline in organ failure parameters Time: Days 1, 3, 5, 7, 14 (+/- 1 day) and 28 (+/- 2 days) or until discharge whatever it comes first.Description: Determined as percentage of dead patients
Measure: Proportion of mortality rate Time: Day 28Description: Determined as: Time to invasive mechanical ventilation (if not previously initiated); Time to independence from non-invasive mechanical ventilation; Time to independence from oxygen therapy.
Measure: Analysis of the remission of respiratory symptoms Time: Up to 3 months after last dose of treatmentDescription: by using the same imaging technique (chest X-ray or thoracic CT scan)
Measure: Evaluation of the radiological response Time: at days 1 and 28 (+/- 2 days)Description: determined using oropharyngeal or anal swabs
Measure: Time to first negative in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test Time: within 28 days from study inclusionDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of absolute lymphocyte count (ALC),white blood cell count and white blood cell differential count Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of hemoglobin Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of platelets Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of activated partial thromboplastin time (aPTT) Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of creatinine Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of glucose Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of total bilirubin Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of albumin Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Evaluated using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0), SOFA scores.
Measure: Incidence of adverse events (AEs), incidence of prespecified AEs (safety and tolerability) Time: Up to 28 days after last dose of treatmentThe objective of this study is to evaluate the clinical characteristics and outcomes of critically ill patients with COVID-19 admitted to the intensive care unit. A Multicenter Observational Study.
Description: Mortality 30 days following hospital admission
Measure: Hospital mortality Time: 30 daysDescription: The number of calendar days from the day of admission (counted as 1 day) to day of intensive care unit discharge
Measure: Length of stay in the intensive care unit Time: Through study completion, an average of 30 daysCOVID-19 is a rapidly spreading and very contagious disease caused by a novel coronavirus that can lead to respiratory insufficiency. In many patients, the chest radiograph at first presentation be normal, and early low-dose CT-scan is advocated to diagnose viral pneumonia. Lung ultrasound (LUS) has similar diagnostic properties as CT for diagnosing pneumonia. However, it has the advantage that it can be performed at point-of-care, minimizing the need to transfer the patient, reducing the number of health care personnel and equipment that come in contact with the patient and thus potentially decrease the risk of spreading the infection. This study has the objective to examine the accuracy of lung ultrasound in patients with proven COVID-19 pneumonia.
Description: The diagnostic accuracy of lung ultrasound is more than 90% compared to low-dose CT or chest X-ray for the detection of viral pneumonia in patients with COVID-19 infection.
Measure: Accuracy of the diagnosis of interstitial syndrome by lung ultrasound Time: within 2 weeks after first subject includedDescription: The interobserver variability by lung ultrasound between the 2 observers for the diagnosis of interstitial syndrome by lung ultrasound is > 0.6 measured by the Kappa score
Measure: Inter-observer variability Time: within 2 weeks after first subject includedThe COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 pneumonia. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 pneumonia patients, especially the critically ill cases. The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic MSCs. We proposed that the adoptive transfer therapy of MSCs might be an ideal choice to be used. We expect to provide new options for the treatment of critically ill COVID-19 pneumonia patients and contribute to improving the quality of life of critically ill patients.
Description: Improvement and recovery time of inflammatory and immune factors
Measure: The immune function (TNF-α 、IL-1β、IL-6、TGF-β、IL-8、PCT、CRP) Time: Observe the immune function of the participants within 4 weeksDescription: Evaluation of Pneumonia change
Measure: Blood oxygen saturation Time: Monitor blood oxygen saturation of the participants within 4 weeksDescription: Marker for efficacy of treatment
Measure: Rate of mortality within 28-days Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Evaluation of Pneumonia change
Measure: Size of lesion area by chest imaging Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Marker of Immunology and inflammation
Measure: CD4+ and CD8+ T cells count Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Degree of infection
Measure: Peripheral blood count recovery time Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Indirect response to lung function
Measure: Duration of respiratory symptoms (fever, dry cough, difficulty breathing, etc.) Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Clearance time of COVID-19 in participant
Measure: COVID-19 nucleic acid negative time Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Since December 2019, a new agent, the SARS-Cov-2 coronavirus has been rapidly spreading from China to other countries causing an international outbreak of respiratory illnesses named COVID-19. In France, the first cases have been reported at the end of January with more than 60000 cases reported since then. A significant proportion (20-30%) of hospitalized COVID-19 patients will be admitted to intensive care unit. However, few data are available for this special population in France. We conduct a large observational cohort of ICU suspected or proven COVID-19 patients that will enable to describe the initial management of COVID 19 patients admitted to ICU and to identify factors correlated to clinical outcome.
Description: Mortality at day 28
Measure: Mortality at day 28 Time: day 28Description: severe complications (pulmonary embolism, acute kidney injury, myocarditis, cardiac arrest, liver failure, ventilator associated pneumonia) Yes / No
Measure: severe complications Time: up to day 28Description: Delay in imaging in hours
Measure: Imaging Time: day 1Description: delay in microbiological diagnosis in hours
Measure: Delay in Microbiological diagnosis Time: day 1Description: Antiviral therapy Yes / no
Measure: Antiviral therapy Time: up to day 28Description: Antibiotic therapy Yes / No
Measure: Antibiotic therapy Time: day 28Description: Covid-19 treatments Yes / No
Measure: Covid-19 treatments Time: up to day 28Description: number
Measure: Patients receiving renal replacement therapy Time: up to day 28Description: number
Measure: Patients receiving mechanical ventilation Time: up to day 28Description: Patient alive at day 28 : yes / No
Measure: Vital status Time: day 28Coronavirus disease 2019 (COVID-19) is an infectious disease responsible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is highly contagious requiring restrictive and stressful measures for patients, family members and ICU healthcare providers. To avoid contagion, patient isolation has become the rule. For patients, these measures add stress to the ICU environment and deprive them of unrestricted family visits. Family members are not only left with fear but also many unanswered questions. In end-of-life situations, many family members are unable to say good-bye and unable to provide support to their loved-one throughout the process. The impact of exclusion or limited inclusion certainly needs to be explored. Moreover, ICU caregivers are having to face new challenges and to work in a unknown situation, juggling with both professional issues such as increased workload, working longer hours and safety issues, and personal issues such as child care and transport as well as family transmission of the virus. The main objective of this study is to demonstrate that the COVID-19 pandemic, as compared to seasonal flu and community acquired pneumonia, significantly increases post-traumatic stress disorder (PTSD) in family members of critically ill patients. PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge. The IES-R is a 22-item self-report measure that assesses subjective distress caused by traumatic events. It will be compared across the three groups (COVID-19, FLU and CAP).
Description: Proportion of Family members with IES-R> 22 PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge of corresponding patient. It si a scale ranging from 0 to 88. Weiss, DS.; Marmar, CR. The impact of event scale - revised. In: Wilson, JP.; Keane, TM., editors.Assessing psychological trauma and PTSD. New York: Guilford Press; 1997. p. 399-411
Measure: PTSD Family members sup 22 Time: 90 daysDescription: Among Family members PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)
Measure: PTSD Family members Time: 90 daysDescription: Among Patients PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)
Measure: PTSD Patients Time: 90 daysDescription: Among healthcare providers PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)
Measure: PTSD healthcare providers Time: 2 months after official end of the Covid-19 peakDescription: Among Family members Symptoms of anxiety and depression using the HADS scale
Measure: HADS Family members Time: 90 daysDescription: Among Patients Symptoms of anxiety and depression using the HADS scale
Measure: HADS Patients Time: 90 daysDescription: Among Patients Mental and physical health-related quality of life as assessed by the SF36
Measure: SF36 Patients Time: 90 daysDescription: Among Family members Questionnaire describing their experience of the patient's ICU hospitalization
Measure: Questionnaire Family members Time: 90 daysDescription: Among Patients Questionnaire describing their experience of the patient's ICU hospitalization
Measure: Questionnaire Patients Time: 90 daysDescription: Among healthcare providers Questionnaire describing their experience of the patient's ICU hospitalization
Measure: Questionnaire healthcare providers Time: 2 months after official end of the Covid-19 peakDescription: Among healthSymptoms of burnout on MBI scale as assessed by the Maslash Burnout Inventorycare providers
Measure: MBI healthcare providers Time: 2 months after official end of the Covid-19 peakDescription: Job Strain as assessed by the Karasec instrument
Measure: Karasec instrument healthcare providers Time: 2 months after official end of the Covid-19 peakClinical thoracic ultrasound plays an important role in the exploration, diagnosis and follow-up of thoracic pathologies. The COVID (Coronavirus Disease) epidemic is leading to a large influx of patients in the emergency department with respiratory disorders. The rapid diagnosis of respiratory disorders in infected patients is important for further management. Chest ultrasound has already demonstrated its value in the diagnosis of pneumonia in the emergency department with superiority over chest X-ray. However, there is little data on the thoracic ultrasound semiology of viral pneumonia in general and of COVID in particular.
Description: description of ultrasound abnormalities for Covid-19 patients
Measure: Characteristics of pulmonary ultrasound for Covid-19 patients Time: Day oneDescription: description of ultrasound abnormalities for Covid-19 patients
Measure: Characteristics of pulmonary ultrasound for Covid-19 patients Time: Day 3Description: description of ultrasound abnormalities for Covid-19 patients
Measure: Characteristics of pulmonary ultrasound for Covid-19 patients Time: Day 14Description: description of CT-scan abnormalities for Covid-19 patients
Measure: Charateristics of pulmonary CT-scan for Covid-19 patients Time: Day 1Description: description of CT-scan abnormalities for Covid-19 patients
Measure: Charateristics of pulmonary CT-scan for Covid-19 patients Time: Day 3Description: description of CT-scan abnormalities for Covid-19 patients
Measure: Charateristics of pulmonary CT-scan for Covid-19 patients Time: Day 14This is a double-blind, randomized, placebo-controlled clinical trial. A total of 210 individuals aged over 18 years old, without a diagnosis of severe respiratory disease, who came to the study site with clinical and radiological suspicion of SARS-CoV2, will be randomized into two treatment groups at a 1:1 ratio to receive a 5-day CQ diphosphate tablets or placebo (tablet without active ingredient produced with the same physical characteristics).
Description: Evaluate if CQ diphosphate prevents the onset of SARS in patients on intervention group through standardized questionnaires.
Measure: Proportion of patients with onset of severe acute respiratory syndrome (SARS) Time: 7 days after randomizationDescription: Mortality rate between intervention and placebo group on days 7, 14, and 28 after randomization
Measure: Mortality rate Time: after randomization, up to 28 daysDescription: Proportion of participants in need and duration of intensive care support after randomization
Measure: Number of participants in need of intensive care support Time: during and after intervention, up to 28 daysDescription: Viral load change in blood and oropharyngeal swab samples
Measure: Viral concentration Time: After randomization, up to 7 daysDescription: Incidence of serious adverse events during and after treatment
Measure: Cumulative incidence of serious adverse events Time: During and after intervention, up to 28 daysDescription: Incidence of grade 3 and 4 adverse events during and after treatment
Measure: Cumulative incidence of grade 3 and 4 adverse events Time: During and after intervention, up to 28 daysDescription: proportion of discontinuation or temporary suspension of treatment (for any reason)
Measure: Proportion of patients with discontinued treatment Time: after randomization, up to 28 daysDescription: proportion of patients with increased levels of troponin I
Measure: Incidence of cardiac lesions Time: after randomization, up to 120 daysDescription: proportion and magnitude of QTcF interval increases higher than 500ms
Measure: Incidence of cardiac disfunctions Time: after randomization, up to 120 daysDescription: Changes measured on day 120 will be compared to baseline, through spirometry.
Measure: Change in respiratory capacity Time: Day 120 after randomizationThis is a double-blind, randomized, placebo-controlled, phase IIb clinical trial to assess the efficacy and safety of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 420 individuals of both sexes, aged over 18 years old, with symptoms suggestive or confirmed diagnosis of severe acute respiratory syndrome (SARS), hospitalized at the Hospital and Pronto-Socorro Delphina Rinaldi Abdel Aziz (HPSDRAA), with clinical and radiological findings suggestive of SARS-CoV2 infection, will be randomized at a 1:1 ration to receive either MPS (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).
Description: Mortality rate on day 28, after randomization
Measure: Mortality rate at day 28 Time: on day 28, after randomizationDescription: Number of patients with diagnosis of early onset of SARS
Measure: Proportion of patients with SARS Time: after randomization, up to 7 days.Description: Proportion of patient that died on days 7, 14 and 28.
Measure: Mortality rate on days 7, 14 and 28 Time: after randomization, up to 28 days.Description: proportion of patients requiring orotracheal intubation
Measure: Incidence of orotracheal intubation Time: after randomization, up to 7 days.Description: Proportion of patients with oxygenation index (PaO2 / FiO2) < 100 in 7 days.
Measure: Change in oxygenation index Time: after randomization, up to 7 days.Infection with the SARS-Cov-2 virus, responsible of severe acute respiratory distress syndrome (SARS), is an emerging infectious disease called Covid-19 and declared as pandemic by the World Health Organization on March 11, 2020. This pandemic is responsible of significant mortality. In France, several thousand patients are hospitalized in intensive care units, and their number continues to increase. Mortality during Covid-19 is mainly linked to acute respiratory distress syndrome, which frequency is estimated in France to occur in 6% of infected patients. Comorbidities such as cardiovascular conditions, obesity and diabetes increase susceptibility to severe forms of Covid-19 and associated mortality. Therapeutic management has three components: symptomatic management, including supplementary oxygen therapy and in case of respiratory distress mechanical ventilation; the antiviral approach; and immunomodulation, aiming at reducing inflammation associated with viral infection, which is considered to take part in severe presentations of the disease. During Covid-19 viral pneumonia related to SARS-COv-2, there is a significant release of pro-inflammatory cytokines in the acute phase of viral infection, which could participate in viral pneumonia lesions. In children with less mature immune system than adults, SARS-Cov-2 infection is less severe. The current prevailing assumption is that severe forms of Covid-19 may not only be related to high viral replication, but also to an excessive inflammatory response favoring acute lung injury and stimulating infection. The investigators hypothesize that early control of the excessive inflammatory response may help reducing the risk of acute respiratory distress syndrome. The investigators will evaluate the benefit, safety and tolerability of corticosteroid therapy to reduce the rate of subjects hospitalized for Covid-19 viral pneumonia who experience clinical worsening with a need of high-flow supplemental oxygen supplementation or transfer in intensive care units for respiratory support.
Description: SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask. measured twice at 5-15 min intervalsThe average value of the two measurements will be calculated.
Measure: Number of patients with a theoretical respiratory indication for transfer to intensive care unit evaluated by a SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask. Time: 7 daysDescription: level1: not hospitalized no limited activities, level 7: death
Measure: disease severity assessed on a 7-level ordinal scale Time: 7 daysDescription: Reduction of radiological signs on chest imaging
Measure: radiological signs on chest imaging Time: 7 daysDescription: duration on days
Measure: Duration of oxygen therapy Time: 21 daysSeveral patients with hypoxaemic SARS-CoV2 pneumonia were able to benefit from hyperbaric oxygen treatment (HBOT) in China. In a clinical case published in the Chinese journal of hyperbaric medicine, treatment with repeated HBO sessions prevented admission to intensive care unit with mechanical ventilation in a patient aged 69 who presented with signs of respiratory decompensation. HBOT is the most powerful oxygenation modality in the body today. HBOT can dramatically increase the amount of dissolved oxygen in the blood. HBOT not only promotes blood transport but also its tissue delivery. Furthermore, HBOT has specific immunomodulatory properties, both humoral and cellular, making it possible, for example, to reduce the intensity of the inflammatory response and to stimulate antioxidant defenses by repeating sessions. A virucidal capacity of HBOT might also be involved. HBOT is generally regarded as safe with very few adverse events. Following this feedback, it is proposed in the context of crisis management related to SARS-CoV2 to assess the value of HBO treatment of patients with CoV2 pneumonia. Indeed, it seems essential to propose therapeutic strategies to limit the risk of respiratory decompensation requiring admission to intensive care unit for patients with SARS-CoV2 pneumonia.
Description: Time to normalize the oxygen requirement (oxygeno-dependence), i.e. allowing a pulse oximetry value in ambient air greater than or equal to 92% and / or arterial blood gas with a PaO2 value greater than 60mmHg in ambient air.
Measure: Time to normalize the oxygen requirement (oxygeno-dependence) Time: 1 monthDescription: Number of days with oxygen need, taking into account the predictors of bad outcome
Measure: Days of hospitalization between the HBO group and the control group. Time: 1 monthDescription: Oxygen flow values to obtain a saturation by pulse oximetry greater than or equal to 92% between the OHB group and the control group.
Measure: Oxygen flow values to obtain a saturation by pulse oximetry greater than or equal to 92% values between the HBO group and the control group. Time: 1 monthDescription: Days on invasive mechanical ventilation
Measure: Days on invasive mechanical ventilation Time: 1 monthDescription: Mortality
Measure: Mortality Time: 1 monthDescription: Number of patients requiring a permanent O2 flow rate greater than 6 liters / min with high-speed nasal mask or oxygen therapy or with invasive or non-invasive ventilation
Measure: Number of patients requiring a permanent O2 flow rate greater than 6 liters / min with high-speed nasal mask or oxygen therapy or with invasive or non-invasive ventilation Time: 1 monthNational multicentric observational retrospective case-control study comparing the relative frequency of the various microorganisms responsible for VAP in patients infected or not by SARS-CoV-2 and their resistance to antibiotics.
The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality. Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival. The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.
Description: The time-to-death from all causes within the first 60 days after randomization.
Measure: The time-to-death from all causes Time: day-60Description: the time to need for mechanical ventilation (MV), as defined by any of the 3 criteria for intubation within the first 28 days after randomization.
Measure: The time to need for mechanical ventilation (MV) Time: day-28.Description: The cycle threshold for SARS-CoV-2 PCR at baseline, day 7 and day 10 in samples of the same origin (preferably subglottic i.e. bronchoalveolar lavage or tracheal aspiration, otherwise nasopharyngeal swab)
Measure: The viral load in the respiratory tract Time: day-10Description: Proportion of patients with at least one episode of any healthcare-associated infection between randomization and D28
Measure: Number of patient with at least one episode of healthcare-associated infections Time: day-28Description: To compare the exposition to mechanical ventilation
Measure: Number of days alive without mechanical ventilation Time: day-28Description: Changes in SOFA (Sepsis-related Organ Failure Assessment) score. (min = 0 for normal status max = 24 for worse status)
Measure: Measure of SOFA score Time: day-28Description: to compare the exposition to renal replacement therapy
Measure: Number of days alive without renal replacement therapy Time: day-28Description: To compare the lengths of ICU
Measure: Lengths of ICU-stay Time: day-60Description: To compare the lengths of hospital-stay
Measure: Lengths of hospital-stay Time: day-60Description: Proportion of patients with severe hypoxemia, which is defined as an oxygen saturation of less than 80% during the same interval during the interval between induction and 2 minutes after tracheal intubation
Measure: Number of patients with severe hypoxemia, Time: day 60Description: Proportion of patients with cardiac arrest within 1 hour after intubation
Measure: Number of patients with cardiac arrest within 1 hour after intubation Time: day 60COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent Covid-19 or infection with SARS-CoV-2 or therapeutic agent to treat COVID-19. This protocol CORIMUNO19-COAG will evaluate the efficacy and safety of active anticoagulation using heparin: Tinzaparin (INNOHEP®) or unfractionated heparin (Calciparine®, Héparine Sodique Choay®) in COVID-19 patients hospitalized in conventional or intensive care units. It will use a phase 2 randomized open-label multicentre clinical trial, where patients will be randomly allocated to anticoagulation versus Standard of Care.
Description: group 1
Measure: Survival without ventilation (VNI or mechanical ventilation) Time: day 14Description: group 2
Measure: ventilator free survival Time: day 28Description: range from 0 (healthy) to 10 (death) values below or equal to 5 correspond to the absence of any oxygen supply beside nasal or facial mask
Measure: World Health Organisation(WHO) progression scale ≤5 Time: day 4Description: range from 0 (healthy) to 10 (death)
Measure: World Health Organisation(WHO) progression scale Time: day 4, 7 and 14Description: according to Acute Kidney Injury (AKIN) classification system
Measure: rate of acute kidney injury Time: day 28Description: confirmed by objective testing
Measure: rate of clinically overt pulmonary embolism or proximal deep vein thrombosis Time: day 14 and day 90Description: confirmed by objective testing
Measure: Rate of clinically overt arterial thrombosis Time: day 14 and day 90Description: as a thrombus extending from the catheter into the lumen of the deep vein where the catheter is inserted diagnosed with radiologic imaging in case of a clinical suspicion of upper/lower limb DVT or pulmonary embolism or compulsory catheter removal
Measure: Rate of central venous catheter-related deep vein thrombosis (CVC-DVT) Time: day 28Bevacizumab, ZERIBEV® (Pfizer)/AVASTIN® (Roche) 25 mg/ml ®, is a recombinant humanised monoclonal IgG1 antibody It seems interesting to use bevacizumab in severe patients infected with SARS-CoV-2 requiring hospitalization in conventional unit or in ICU. This protocol CORIMUNO19-BEVA will evaluate the efficacy and safety of AVASTIN®/ ZERIBEV® (bevacizumab) COVID-19 patients hospitalized in conventional units. This phase 2 randomized clinical trial aimed at evaluating the efficacy and safety of AVASTIN®/ ZERIBEV® (bevacizumab) alone versus standard of care (SoC) in patients hospitalized in conventional units.
Description: value of a healthy individual occurs between 95 - 100
Measure: Saturation of Oxygen in the blood (SaO2) Time: day 14Description: value of a healthy individual occurs between 75-100 mmHg
Measure: Arterial oxygen partial pressure (paO2) Time: day 14Description: Normal level should be >500 Index of severity of acute respiratory distress syndrome (ARDS) mild if 200-300 moderate if 100-200 severe if < 200
Measure: Ratio of arterial oxygen partial pressure to fractional inspired oxygen (paO2/FiO2) Time: day 14Description: based on a Likert scale with scores ranging from 1 to 5 (1—definitely no; 2—probably no; 3—equivocal; 4—probably yes; 5—definitely yes)
Measure: CT-scan score Time: day 14Description: measured on an visual analog scale (VAS), ranging from 0 (no dyspnea) to 10 (major dyspnea)
Measure: dyspnea Time: day 28This is an open label clinical study to evaluate the activity of chloroquine phosphate in patients with SARS-CoV-2 virus infection. The study aims to document possible prevention of pneumonia in patients staying at home and in improving the symptoms of SARS-CoV-2 pneumonia in patients who will be hospitalised.
Description: Achieving 50% reduction in symptom score for patients with lower respiratory tract infection on day 8 visit from study initiation.
Measure: 50% reduction in symptom score for patients with lower respiratory tract infection Time: Day 8 visit from study initiationDescription: Lack of progression to lower respiratory tract infection in patients enrolled in the study due to upper respiratory tract infection on day 8 visit from study initiation.
Measure: Lack of progression for patients with upper respiratory tract infection Time: Day 8 visit from study initiationDescription: Lower respiratory tract infection rating takes place. The symptoms checked are: Cough, Chest pain, Dyspnea, expectoration. For each symptom score is given from 0 to 3 depending on the intensity and they are summed.
Measure: Comparison of the primary endpoint with respective patients not receiving the treatment Time: Day 14 visit from study initiationDescription: It is defined as the presence of both of the following: Respiratory quotient (pO2 / FiO2) less than 150 Need for treatment with CPAP or mechanical ventilation
Measure: Serious respiratory failure until day 14. This will be compared with respective patients not receiving the treatment. Time: Day 14 visit from study initiationDescription: Frequency of AEs and SAEs
Measure: Frequency of AEs and SAEs Time: Day 14 visit from study initiationCCAP is an investigator-initiated multicentre, randomized, double blinded, placebo-controlled, multi-stage trial, which aims to assess the safety and efficacy of novel treatment option of moderate-severe COVID-19. Participants will be randomized 1:1:1:1:1:1 to parallel treatment arms: Convalescent plasma, sarilumab, hydroxychloroquine, baricitinib, intravenous and subcutaneous placebo, or oral placebo. Primary outcome is a composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days.
Description: Composite outcome
Measure: All-cause mortality or need of invasive mechanical ventilation Time: 28 daysDescription: Number of participants with adverse events with possible relation to study drug
Measure: Frequency of adverse events Time: 90 daysDescription: Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines
Measure: Frequency of severe adverse events Time: 90 daysDescription: Number of days to improvement of at least 2 categories relative to baseline on the ordinal scale. Categories are as follows: Death; Hospitalized, in intensive care requiring Extracorporeal Membrane Oxygenation (ECMO) or mechanical ventilation; Hospitalized, on non-invasive ventilation or high-flow oxygen device; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities
Measure: Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status Time: 90 daysDescription: Number of days without mechanical ventilation
Measure: Ventilator-free days Time: 28 daysDescription: Number of days without organ-failure
Measure: Organ failure-free days Time: 28 daysDescription: Number of days in ICU
Measure: Duration of ICU stay Time: 90 daysDescription: Number of deaths by any cause
Measure: Mortality rate Time: 7, 14, 21, 28 and 90 daysDescription: Days from the date of hospital admission for COVID-19 to the date of discharge
Measure: Length of hospital stay Time: 90 daysDescription: Days requiring supplement oxygen
Measure: Duration of supplemental oxygen Time: 90 daysThis open-label randomized controlled study will evaluate safety, efficacy, and the pharmacokinetic profile of CM4620-IE in patients with severe COVID-19 pneumonia. Forty patients on low flow oxygen and forty patients on high flow oxygen will receive 2.0 mg/kg of CM4620-IE by continuous IV infusion on Day 1, followed by 1.6 mg/kg for days 2 and 3. Another 20 patients of each will receive local standard of care only. The infusion of CM4620-IE will start within 8 hours from the time the patient or LAR provides informed consent.
Description: The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per protocol study drug administration) 7. Not hospitalized
Measure: Improvement on a 7-point Ordinal Scale Time: Upon enrollment into the study through hospital discharge, up to day 28Description: Defined as the number of participants who experience TEAEs with investigator-specified relationship to CM4620-IE and assessment of severity.
Measure: Incidence of treatment-emergent adverse events (TEAE) (safety and tolerability) Time: from enrollment and up to 60 daysDescription: Defined as the change in the ratio of arterial oxygen partial pressure to fractional inspired oxygen
Measure: Change in estimated PaO2/FiO2 Time: from enrollment and up to day 28Description: Defined as the number of days that a participant is both alive and free of mechanical ventilation
Measure: Number of days alive and free of mechanical ventilation Time: from enrollment and up to day 60Description: Defined as the number of days from hospital admission to discharge alive from the hospital
Measure: Time to discharge alive from hospital Time: From day 1 of hospital admission to hospital discharge, up to day 28Description: Measurement of IL-6 levels in patient blood
Measure: Change in interleukin (IL)-6 level Time: from enrollment until day 10Description: Measurement of IL-17 levels in patient blood
Measure: Change in IL-17 level Time: from enrollment until day 10Description: Measurement of tumor necrosis factor-alpha in patient blood
Measure: Change in tumor necrosis factor-alpha level Time: from enrollment until day 10Description: Measurement of cytokines in patient blood
Measure: Change in cytokine levels Time: from enrollment until day 10Description: Concentration measured using a validated assay
Measure: CM4620-IE serum concentration Time: enrollment through 72 hoursDescription: Measurement of procalcitonin in patient blood
Measure: Procalcitonin levels Time: from enrollment through day 28Description: Defined as the time to peripheral capillary oxygen saturation (SpO2) >94% sustained for at least 24 hours
Measure: Normalization of oxygen saturation Time: from enrollment until day 28Description: Defined as the time to peripheral capillary oxygen saturation (SpO2) >94%
Measure: Time to first normalization of oxygen saturation Time: from enrollment until day 28Double blinded randomized clinical trial designed to evaluate the efficacy and safety of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with confirmed COVID-19 pneumonia.
Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points (score range from 1 to 7 , with 7 being the worst score)
Measure: Time to clinical improvement of at least 1 level on the ordinal scale between Day 1 (day of the first administration of study drug) to Day 11 (day after last day of treatment). Time: up to Day 11Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points at day 15 and day 29
Measure: Clinical status assessed by ordinal scale Time: up to Day 29Description: Necessity for transfer to Intensive care unit
Measure: transfer to ICU Time: up to Day 29Description: days from admission to hospital discharge
Measure: Length of hospital day Time: up to Day 29Description: incidence of all-cause mortality
Measure: Hospital Mortality Time: Day 29Description: Need to mechanical ventilation
Measure: Need to Mechanical Ventilation Time: up to Day 29Description: adverse reactions
Measure: Occurence of grade 3-4 adverse event Time: up to Day 29Description: ECG
Measure: QTc Lengthening Time: up to Day 11Description: Thoracic CT scan : number and size of ground-glass opacifications on day 1 and day 11 Two independent pulmonary imagery experts will assess abnormalities according to a standardized framework
Measure: Evolution of pulmonary CT scan images Time: up to Day 11In absence of vaccine and medications specifically designed to treat SARS-CoV-2 disease, identifying treatment options is critical at this time to control the disease outbreak. For this, we have designed a phase II trial of efficacy and safety with 3 branches of different combinations of treatment to identify which is the best early treatment option for patients with pneumonia due to SARS-CoV-2 (Covid-19) Identifying treatment options as early as possible is critical to the SARS-CoV-2 outbreak response. Currently, there is no approved vaccine for the disease and the treatments being used are not specifically designed for the SARS-CoV-2 virus, but are different groups of drugs used for other pathologies with mechanisms of action that justify their use because they inhibit entry of the virus into virus cells or proteases. The study aims to compare lopinavir / ritonavir (200 /50), imatinib 400mg, baricitinib 4mg, in combination with hydroxychloroquine 200mg, administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment. Patients who meet inclusion criteria and do not have any exclusion criteria will be randomized to receive open treatment 1:1:1
Description: time from inclusion to improvement by 2 points on the "seven-category ordinal scale" or high, whichever comes first
Measure: time to clinical improvement Time: baseline to day 14Description: number of serious adverse effects and premature discontinuation of treatment
Measure: Safety of treatments Time: through study completion, an average of 1 monthDescription: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Measure: Tolerability of treatments Time: during treatment and up to 30 days after the last treatment doseDescription: Possible biomarkers and genetic markers of susceptibility to SARS-CoV-2 using high-performance techniques with serum DNA from the participants
Measure: Biomarkers and genetic markers of susceptibility to SARS-CoV-2 Time: baselineThe 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID 19), which originated in Wuhan, China, has become a major concern all over the world. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite any attempted treatment.. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease. The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Plasma-exchange is expensive and requires large volumes of substitution fluid. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion. With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The aforementioned limitations of plasma therapy can be overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP).DFPP is a modality of plasma purification that performs an initial plasma separation from blood, and the subsequent separation of specific molecules, on the basis of their specific molecular weight (cut-off), by using a fractionation filter. The Fractionation Filter 2A20, because of its membrane sieving cut-off, retains larger molecules and returns plasma along with smaller molecules to the circulation, including the major part of the albumin. The selection of the membrane 2A20 is related to the appropriate Sieving Coefficient for IgG that allows to efficiently collect antibodies from patients which are recovered from COVID-19, with negligible fluid losses and limited removal of albumin. The total amount of antibodies obtained during one DFPP session exceeds by three to four times the total amount provided to recipients with one unit of plasma obtained during one plasma-exchange session from one COVID-19 convalescent donor. This should result in more effective viral inhibition and larger benefit for the patient achieved with one unit of enriched immunoglobulin solution obtained with DFPP than with one unit of plasma obtained with plasma exchange. These observations provide the background for a pilot study aimed to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for critically ill patients with severe coronavirus (COVID-19) pneumonia requiring mechanical ventilation.
The purpose of the study is to evaluate an effectiveness of the drug Dalargin for the prevention and treatment of severe pulmonary complications symptoms associated with severe and critical coronavirus infection cases (SARS COVID19, expanded as Severe acute respiratory syndrome Cоrona Virus Disease 2019 ). Test drug that will be administered to patients are: - Dalargin, solution for inhalation administration, - Dalargin, solution for intravenous and intramuscular administration.
Description: Estimated by Polymerase chain reaction (PCR)
Measure: The change of viral load in patients with SARS-COVID-19. Time: Upon patient inclusion in the study, after 96 hours and on the 10day;Description: Assessed through the entire patient participation in the study
Measure: The frequency of development of Acute Respiratory Distress Syndrome (ADRS) Time: up to 10 daysDescription: The number of days a patient is hospitalized
Measure: Duration of hospitalization Time: up to 10 daysDescription: Early mortality from all causes will be estimated
Measure: The frequency of early mortality Time: up to 30 daysDescription: Late mortality from all causes will be estimated
Measure: The frequency of late mortality Time: up to 90 daysDescription: Clinical status at the time of completion of participation in the study will be estimated based upon the following criteria: Death; Hospitalization is extended, on invasive mechanical ventilation of the lungs with extracorporeal membrane oxygenation; Hospitalization extended, on non-invasive ventilation; Hospitalization is extended, needs additional oxygen; Hospitalization is extended, additional oxygen is not required; Discharged.
Measure: Clinical status at the time of completion of participation in the study Time: an average of 10 daysStudy of the effectiveness and safety of the drug Mefloquine, tablets 250 mg, produced by FSUE "SPC" Farmzaschita " FMBA of Russia (Russia), in comparison with the drug Hydroxychloroquine, tablets 200 mg, for the treatment of patients with coronavirus infection, in the "off-label" mode, to make a decision on the possibility of expanding the indications for use.
Description: The number of patients with development of respiratory failure requiring transfer to the ICU.
Measure: 1st primary endpoint for group 1 Time: up to 10 daysDescription: The period of clinical recovery.
Measure: 2nd primary endpoint for group 1 Time: up to 10 daysDescription: The period of clinical recovery.
Measure: 1st primary endpoint for group 2 Time: up to 10 daysDescription: Frequency of fatal outcomes associated with coronavirus infection disease (COVID19)
Measure: 2nd primary endpoint for group 2 Time: through study completion, an average of 3 monthsDescription: A change in viral load by conducting PCR assay through different timeframes
Measure: 1st secondary endpoint for group 1 Time: on days 5 and 10Description: Frequency of clinical cure on day 10 from the start of therapy
Measure: 2nd secondary endpoint for group 1 Time: on day 10Description: The retention time of the reaction temperature from the start of the treatment.
Measure: 3d secondary endpoint for group 1 Time: up to 10 daysDescription: Concentration of C-reactive protein in blood plasma.
Measure: 4th secondary endpoint for group 1 Time: up to 10 daysDescription: Respiratory index.
Measure: 5th secondary endpoint for group 1 Time: up to 10 daysDescription: Frequency appearance unwanted phenomena and serious unwanted phenomena
Measure: 6th secondary endpoint for group 1 Time: up to 10 daysDescription: A change in viral load by conducting PCR assay through different timeframes
Measure: 1st secondary endpoint for group 2 Time: on days 5 and 10Description: Respiratory index.
Measure: 2nd secondary endpoint for group 2 Time: up to 10 daysDescription: The retention time of the reaction temperature from the start of treatment.
Measure: 3d secondary endpoint for group 2 Time: up to 10 daysDescription: Concentration of C-reactive protein in blood plasma.
Measure: 4th secondary endpoint for group 2 Time: up to 10 daysDescription: Number of patients required transition to alternative therapy schedule
Measure: 5th secondary endpoint for group 2 Time: up to 10 daysDescription: Frequency of adverse events and serious adverse events
Measure: 6th secondary endpoint for group 2 Time: up to 10 daysSince end of December, a new coronavirus, close to the 2002 SARS coronavirus, cause serious pneumonias throughout world. There is currently no strong evidence of an efficient specific treatment. Hydroxychloroquine is an old chloroquine-derived drug, prescribed for auto-immune disorders. It has shown efficacy against Sars-CoV-2 in vitro. Some studies showed that Hydroxychloroquine might improve the clinical status of Sars-CoV-2 infected patients. Azithromycin is a macrolide antibiotic, with immunomodulatory properties. Adding Azithromycin to a hydroxychloroquine-based treatment showed an apparent accelerated viral clearance in infected patients. This study wants to evaluate the clinical impact of adding Azithromycin to Hydroxychloroquine in the treatment of Sars-CoV-2 pneumonia
Description: A significant hypoxemia is an arterial partial pressure of oxygen of less than 60 mmHg despite an oxygen flow of more than 6 L/min, patient at rest.
Measure: Rate of patients reaching a significant hypoxemia, in each arms. Time: From day 0 to day 7The study is configured as a retrospective and prospective observational study. The study will be multi-center and will involve all COVID-19 pneumonia patients treated with canakinumab administered subcutaneously.
Description: percentage of patients treated with canakinumab sc who do not require intensive care treatment during hospitalization for COVID-19
Measure: intensive care treatment Time: 9 monthsDescription: ICU stay times
Measure: ICU stay times Time: 9 monthsDescription: percentage of patients who died 1 month after treatment
Measure: % died after 1 month after treatment Time: 9 monthsDescription: time of hospitalization
Measure: hospitalization Time: 9 monthsDescription: number of adverse event
Measure: adverse event Time: 9 monthsMortality of COVID-19 pneumonia with acute respiratory distress syndrome (ARDS) is extremely high in preliminary reports amounting to 50-60%. Duration of mechanical ventilation in these patients appears to exceed standard duration of mechanical ventilation in non-COVID-19 ARDS patients, suggesting that COVID-19 patients may be particularly at risk for ventilator-induced lung injury. Treatment of COVID-19 ARDS patients is to date mainly supportive with protective mechanical ventilation (ventilation with low tidal volume (VT) i.e. 6 ml/kg of predicted body weight (PBW) and plateau pressure control below 30 cm H2O). Mechanical ventilation with VT reduction below 6 ml/kg PBW in ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury. Investigators recently performed a multicenter pilot study on 34 moderately severe to severe ARDS patients. This study demonstrated that ultraprotective ventilation with ultra-low VT (≤4.2 ml/kg PBW) without extracorporeal circulation may be applied in approximately 2/3 of the patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients. Investigators hypothesized that ultraprotective ventilation without extracorporeal circulation may reduce the mortality at day-90 and increase the number of days free from mechanical ventilation (VFD) at day-60, as compared to protective ventilation.
Description: For an alive patient at day 90, the score will be built as follow: a value +1 will be given for comparisons to dead patients and alive patients with a lower number of VFD. For comparisons to alive patients with a higher number of VFD a value -1 will be given and in case of identical number of VFD a value 0 will be given. For a dead patient a value -1 will be given for comparisons to alive patients and 0 for comparisons to dead patients. For a given patients the score will correspond to the sum of values resulting to the comparison to all patients of the other group. A higher score indicates a more favorable result.
Measure: A composite score based on all-cause mortality and the number of ventilator free-days (VFD) Time: Day 90Description: All-cause mortality with analysis in intention to treat, i.e. each patient will be analyzed in his initial randomization group regardless of whether the allocated strategy was effectively applied or not.
Measure: All-cause mortality (intention to treat) Time: 90-day after inclusionDescription: VFD will be computed as follows from the day of inclusion: VFD= 0 if the patient dies between inclusion and day 60 VFD = 60-x if the patient is successfully weaned from invasive mechanical ventilation x days after inclusion. Successful weaning from mechanical ventilation is defined by extubation without reintubation within at least 48 hours (or weaning from mechanical ventilation for at least 48 hours in patients with tracheostomy) VFD= 0 if the patient is mechanically ventilated for more than 60 days after inclusion
Measure: Ventilator-free days (VFD) Time: day 60 after inclusionDescription: Per protocol analysis will be carried out by comparing the group of patients in whom median daily tidal volume from inclusion to weaning of deep sedation will be lower of equal to 4.2 ml/kg of predicted body weight to the group of patients in whom median tidal volume from inclusion to weaning of deep sedation will be greater than 4.2 ml/kg of predicted body weight, whatever the patients' initial randomization group. Weaning of deep sedation is defined by a Richmond Agitation Sedation (RASS) score greater than -3 for at least 48 hours.
Measure: All-cause mortality with per protocol analysis Time: 90-dayDescription: Successful extubation is defined by extubation without reintubation within at least 48 hours (or weaning from mechanical ventilation for at least 48 hours in patients with tracheostomy) Data will be right censored at 60 days and death will be taken into account as a competing risk.
Measure: Time to successful extubation Time: 60 daysDescription: Data will be right censored at 90 days and death will be taken into account as a competing risk.
Measure: Length of hospital stay Time: 90 daysDescription: Weaning of deep sedation is defined by a Richmond Agitation Sedation (RASS) score greater than -3 for at least 48 hours.
Measure: Respiratory parameters assessed daily from inclusion to weaning of deep sedation or 14 days whichever comes first Time: 14 daysDescription: Doses of the following drugs used for deep sedation will be assessed daily: midazolam, propofol and opioid. Opioid dose will be expressed as morphine equivalent with the following conversion factor: 1µg of sufentanil = 10 µg of fentanyl = 1 mg of morphine
Measure: Daily sedation dose during the first 14 days of the study Time: 14 daysDescription: Rescue therapies are any therapy among the following ones: neuromuscular blocking agents, prone position, nitric oxide, recruitment maneuvers, ECMO
Measure: Rate of use of rescue therapies Time: 14 daysDescription: Severe mixed acidosis is defined by the association of pH<7.15 and PaCO2>45 mm Hg.
Measure: Incidence density rate of severe mixed acidosis Time: ICU stayDescription: Ventilator associated pneumonia will be defined as any pneumonia acquired under mechanical ventilation after inclusion.
Measure: Incidence density rate of ventilator associated pneumonia Time: ICU stayDescription: Acute cor pulmonale is defined by the association of right ventricle dilatation (right ventricle surface / left ventricle surface >0,6) and septal dyskinesia assessed by echocardiography
Measure: Incidence density rate of acute cor pulmonale Time: ICU stayDescription: Barotrauma is defined by any pneumothorax OR pneumomediastinum OR subcutaneous emphysema, OR pneumatocele of more than 2 cm detected on image examinations.
Measure: Incidence density rate of barotrauma Time: ICU stayDescription: Serious adverse event is any life threatening event OR any event resulting in death.
Measure: Incidence density rate of any serious adverse events Time: ICU stayDescription: The Telephone Montreal Cognitive Assessment score will be assessed by phone call. The total score ranges from 0 to 30; higher scores being associated to a better outcome.
Measure: Cognitive impairment assessed by phone call using the Telephone Montreal Cognitive Assessment (T-MoCA) test Time: Day 365 after inclusionDescription: The RAND 36-Item Health Survey (SF-36) score will be assessed by phone call. The score ranges from 0 to 100; higher scores being associated to a better outcome.
Measure: Quality of life assessed by the RAND 36-Item Health Survey (SF-36) score Time: Day 365 after inclusionDescription: The Impact of Event Scale - revised (IES-R) score will be assessed by phone call. The total score ranges from 0 to 88; higher scores being associated to a worse outcome.
Measure: Post-traumatic stress disorder assessed by the Impact of Event Scale - revised (IES-R) score by phone call Time: Day 365 after inclusionDescription: The cost-efficacy ratio will be computed as the ratio of cost difference on efficacy difference between the intervention arm and the reference arm. The costs taken into account will be the direct hospitalized costs. The efficacy will be assessed as the number of days alive free from mechanical ventilation.
Measure: Cost-efficacy ratio of the innovative strategy compared to the reference strategy Time: Day 90 after inclusionThe primary objective of this study is to assess whether the use of lenzilumab in addition to current standard of care (SOC) can alleviate the immune-mediated cytokine release syndrome (CRS) and prevent progression to respiratory failure and/or death in high risk patients with COVID-19 pneumonia.
Description: Acute respiratory distress syndrome defined as new or worsening respiratory symptoms with PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 315, chest imaging (radiograph, CT scan, or lung ultrasound) revealing bilateral opacities and pulmonary infiltrates not fully explained by fluid overload or cardiac failure
Measure: Incidence of acute respiratory distress syndrome (ARDS) Time: Up to 28 daysDescription: Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measure: Percentage of Participants Experiencing Adverse Events Time: Up to 60 daysDescription: Using the NCI CTCAE version 5.0
Measure: Percentage of Participants Experiencing Serious Adverse Events Time: Up to 60 daysThe aim of this study is to evaluate the safety and efficacy of autologous adipose-derived mesenchymal cells for treating confirmed or suspected patients with SARS-CoV-2 and compromised respiratory function requiring hospitalization. The hypothesis of the Study is autologous adipose-derived mesenchymal cells given IV to eligible patients will improve clinical outcomes of COVID 19 positive patients with severe pneumonia or ARDS by reducing or avoiding cytokine storm.
Description: Incidence of unexpected adverse events within 28 days following IV administration of MSCs.
Measure: Safety - Incidence of unexpected adverse events Time: up to 28 daysDescription: Changes in progression or rate of subjects progressing to mechanical ventilation
Measure: Efficacy - Frequency of progression to mechanical ventilation Time: up to 28 daysDescription: Changes in time subjects remain on mechanical ventilation
Measure: Efficacy - Changes in length of mechanical ventilation Time: up to 28 daysDescription: Changes in length of time subjects wean off of mechanical ventilation
Measure: Efficacy - Changes in length of weaning of mechanical ventilation Time: up to 28 daysDescription: Length of Hospital Stay
Measure: Efficacy - Changes in length of hospital stay Time: up to 28 daysDescription: Mortality rate from all causes
Measure: Efficacy - Changes in mortality rate Time: up to 28 daysCurrently there is a great need for an accurately and rapid assessment of patients suspected for Covid-19. Like CT, Lung Ultrasound (LUS) examination can potentially help with the initial triage of patients but also help track the evolution of the disease. LUS can be used in every setting, including settings with limited infrastructure, allowing the reduction of disparities in trials participation. LUS is also a practical approach that can be used by obstetricians/gynecologists, who are the primary care givers in the labour and delivery room. The International Lung UltraSound Analysis (ILUSA) Study is an international multicenter prospective explorative observational study to assess the predictive value of LUS in Covid-19 suspected and diagnosed pregnant patients.
Description: The primary endpoint is diagnostic performance in terms of the area under the receiver operating characteristic curve (AUC, also known as the c-statistic) and sensitivity and specificity with regard to the prediction of poor outcome. Outcome at one week from admission: good outcome includes discharge or inpatient breathing in free air; poor outcome includes patient with oxygen support, patients with CPAP/ high oxygen flow cannula, or patient with endotracheal intubation during the week.
Measure: Diagnostic performance of LUS to predict poor outcome Time: outcome one week after enrollment into the studyCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the disease progresses, a series of acute complications tend to develop in multiple organs. Beyond the supportive care, no specific treatment has been established for COVID-19. The effectiveness, both short-term and long-term, of some promising antivirals, such as the hydroxychloroquine combination with azithromycin, needs to be evaluated. This study aims to investigate the predictive role of cardiac biomarkers and pulmonary symptoms for late complications of COVID-19 coronavirus infection on the heart and lung in patients treated with the hydroxychloroquine / azithromycin combination therapy. Thus, COVID-19 coronavirus patients undergoing hydroxychloroquine / azithromycin combination therapy will be compared to patients not undergoing this therapy. The comparison will be made by the analysis of the relationships between (1) levels of ultrasensitive cardiac troponins collected at the beginning of the infection and cardiac magnetic resonance data in the 3rd and 12th months of troponin collection and (2) findings CT scans and the results of the ergospirometers tests performed in those same periods. It is expected to demonstrate that: (1) cardiac troponin and lung tomographic findings can predict late complications of COVID-19 coronavirus infection in the heart and lung, assessed by cardiac magnetic resonance and ergospirometers one year after the beginning of the infection, and (2) hydroxychloroquine / azithromycin combined therapy can abolish the onset of these complications late. Furthermore, the results may point to the need for more rigorous monitoring of cardiologists and pulmonologists of these patients, due to the risk of hemodynamic complications, arrhythmogenic and respiratory.
Description: presence of fibrosis on cardiac resonance and / or decreased functional capacity on ergospirometry
Measure: Fibrosis Time: 12 monthsDescription: Decreased functional capacity on ergospirometers
Measure: Ergospirometers Time: 12 monthesIn the current situation it is of great importance to discover a safe, cost-effective and available treatment strategy in order to limit the rapidly spreading SARS-Cov-2. Recent studies have shown that hydroxychloroquine could have a role in the treatment of infected patients. It is however not very likely that hydroxychloroquine alone could be adequate for treatment of Covid-19 disease. Effective therapy that prevents the virus entrance should contain at least TMPRSS2 inhibitor or a competitive inhibitor of viral ACE 2 binding. The use of bromhexine at the dose adequate to selectively inhibit the TMPRSS2, resulting in preventing of viral entrance via TMPRSS2-specific pathway, coud be an effective treatment of Covid-19. In our study we would like to explore the therapeutic potential of bromhexin and hydroxychloroquine in Covid-19 patients. Hypothesis 1. Combined treatment with bromhexin and hydroxychloroquine shortens the course of disease in hospitalized Covid-19 patients compared to hydroxychloroquine alone. 2. Combined treatment with bromhexin and hydroxychloroquine lowers the incidence of secundary pulmonary infections in hospitalized Covid-19 patients compared to hydroxychloroquine alone. 3. Combined treatment with bromhexin and hydroxychloroquine decreases the need for ICU admission in hospitalized Covid-19 patients compared to hydroxychloroquine alone.
Description: number of days the patient is treated in the hospital
Measure: Duration of hospitalization Time: through study completion, an average of 6 monthsDescription: Number of days from the onset of symptoms to hospital discharge
Measure: Duration of disease Time: through study completion, an average of 6 monthsDescription: Incidence of HAP
Measure: Hospital-aquired pneumonia Time: through study completion, an average of 6 monthsDescription: Number of days spent in the ICU
Measure: ICU stay duration Time: through study completion, an average of 6 monthsDescription: number of days on oxygene therapy
Measure: Oxygene therapy duration Time: through study completion, an average of 6 monthsDescription: Number of hours on mechanical ventilation
Measure: Mechanical ventilatory support duration Time: through study completion, an average of 6 monthsCaptopril being an effective drug available in liquid preparation, administration by nebulization could be of interest for maximizing lung action and minimizing systemic side effects. Such a treatment might be used for "Covid-19" patients with pneumonia in order to avoid ARDS.
Description: To assess determine the efficacy of captopril nebulization addition to standard of care compared to standard of care in term of 14-day ventilation free survival
Measure: Efficacy of captopril nebulization addition to standard of care compared to standard of care. Time: 14 DaysThis protocol provides access to eculizumab treatment for participants with severe COVID-19.
Randomized, prospective, controlled open label clinical trial aimed at investigating if the addition of inhaled corticosteroids (budesonide) reduces treatment failure (defined as a composite variable by the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) according to hospital standard of care guidance) at day 15 after initiation of therapeutic intervention.
Description: composite variable that includes the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) at day 15 after initiation of therapeutic intervention
Measure: Proportion of patients in both arms fulfilling the criteria for treatment failure Time: 15 days after treatmentDescription: Yes/no
Measure: ICU admission Time: baseline, day 3, day 7, day 15, day 30Description: yes/no and reason
Measure: ICU refusal Time: baseline, day3, day 7, day 15, day 30Description: infectious cardiovascular and /or metabolic complications as well as variation in the 7 point WHO scale.
Measure: Occurrence of complications Time: baseline, day3, day 7, day 15, day 30Description: U/L
Measure: lactate dehydrogenase (LDH) Time: at baseline, day 3, day 7, day 15, day 30Description: mg/dL
Measure: C Reactive Protein (CRP) Time: at baseline, day 3, day 7, day 15, day 30Description: ng/mL
Measure: ferritin Time: at baseline, day 3, day 7, day 15, day 30Description: ng/mL
Measure: D-dimer Time: at baseline, day 3, day 7, day 15, day 30Description: x10^9/L
Measure: leukocyte counts Time: at baseline, day 3, day 7, day 15, day 30This is an open-label, controlled, single-centre pilot study of nivolumab in adult patients with COVID-19. This clinical study aims to evaluate efficacy of anti-PD1 antibody in relation to viral clearance and its safety.
Description: Viral load changes in NPS based on SARS-CoV-2 RT-PCR
Measure: Viral clearance kinetics Time: From diagnosis to recovery, assessed up to 6 monthsDescription: Incidence and severity of treatment-related adverse events
Measure: Treatment-related adverse events of nivolumab (Intervention arm only) Time: Up to 1 year after nivolumab dosingDescription: Changes in lymphocyte counts
Measure: Lymphocyte kinetics Time: On days 1, 4, 6, 8, 10 and 28 from study enrollmentDescription: Changes in cytokine levels (e.g. IL-1B, IL-2, IL-6, TNFa)
Measure: Cytokine kinetics Time: On days 1, 4, 6, 8 and 10 from study enrollmentThe aim of this study is to evaluate the efficacy of pulmonary physiotherapy on respiratory functions in hospitalized patients with Novel Coronavirus 2019 pneumonia. Patients will be randomized into 1) intervention group: receiving pulmonary physiotherapy technique to improve pulmonary function and walking training or 2) control group: Usual medical care. Patients in both groups will receive therapeutic incentive spirometer. Various outcome measurements of pulmonary functions will be evaluated before and after of interventions. Mortality rate, hospitalization duration and re-admission will be followed until one month after end of intervention. Also, patient's quality of life will be measured after one month.
Description: Partial pressure of oxygen in mixed venous blood.
Measure: Mixed venous O2 pressure (PVO2) Time: BaselineDescription: Partial pressure of oxygen in mixed venous blood.
Measure: Mixed venous O2 pressure (PVO2) Time: Day 3Description: Partial pressure of carbon dioxide in mixed venous blood.
Measure: Mixed venous CO2 pressure (PVCO2) Time: BaselineDescription: Partial pressure of carbon dioxide in mixed venous blood.
Measure: Mixed venous CO2 pressure (PVCO2) Time: Day 3Description: Measure of the venous blood acidity or alkalinity
Measure: PH Time: BaselineDescription: Measure of the venous blood acidity or alkalinity
Measure: PH Time: Day 3Description: The amount of bicarbonate ion in the venous blood
Measure: HCO3 Time: BaselineDescription: The amount of bicarbonate ion in the venous blood
Measure: HCO3 Time: Day 3Description: The amount of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the venous blood
Measure: Oxygen saturation (O2 Sat) from VBG Time: BaselineDescription: The amount of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the venous blood
Measure: Oxygen saturation (O2 Sat) from VBG Time: Day 3Description: The distance a patient can walk during three minute
Measure: Three minute walk test Time: BaselineDescription: The distance a patient can walk during three minute
Measure: Three minute walk test Time: Day 3Description: The number of dead subjects compared to total patients
Measure: Mortality rate Time: until one monthDescription: Patients' hospitalization after discharge due to any reason
Measure: Number of participants with Rehospitalization Time: until one mothDescription: Using Short-form 36 questionnaire. The minimum score is 0 and the maximum score is 100. Higher scores mean patient's better quality of life.
Measure: The Health-Related Quality of Life (HRQOL) Time: One month after end of interventionDescription: The amount of shortness of breath using Visual Analogue Scale (VAS). The minimum score is 0 and maximum is 10. The 0 score means no breathlessness and the 10 score is the maximum breathlessness.
Measure: breathlessness Time: BaselineDescription: The amount of shortness of breath using Visual Analogue Scale (VAS). The minimum score is 0 and maximum is 10. The 0 score means no breathlessness and the 10 score is the maximum breathlessness.
Measure: breathlessness Time: Day 3The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 3.6%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management. In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.
Description: Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).
Measure: Rate of endotracheal intubation Time: 7 daysDescription: safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater than 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography.
Measure: Discontinuation rate of the treatment Time: 28 daysA national, observational, longitudinal, non-interventional program aiming to identify prognostic parameters, to investigate the kinetics of the immune response, and to identify predictive biomarkers in SARS-CoV-2 infected patients.
Description: Blood samples drawn from the infected participants will be analysed for prognostic parameters.
Measure: Identification of prognostic parameters for SARS-CoV-2 infected participants. Time: 7 monthsDescription: Systems from Abbott and Euroimmun will be used for IgG and IgM in SARS-CoV-2.
Measure: Investigation of the kinetics of immune activation and antibody production against SARS-CoV-2 and correlation with clinical course Time: 7 monthsDescription: Genomic, proteomic, and transcriptomic analyses will be performed on the blood samples drawn from Covid-19 infected participants over the course of 6 months.
Measure: Identification of predictive biomarker/s for clinical course in mildly and severely affected Covid-19 patients using genomic, proteomic, and transcriptomic approach. Time: 7 monthsTwo recent studies have suggested that in patients with Covid19, treatment with hydroxychloroquine may shorten the duration of symptoms and improve viral clearance, an effect that appears most pronounce when combined with azithromycin. Hydroxychloroquine treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation. The purpose of the study is to determine if oral hydroxychloroquine monotherapy, or in combination with azithromycin results in clinical benefit in patients hospitalized with COVID19 pneumonia.
Description: To demonstrate in patients receiving standard of care that the percentage who achieve clinical response with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo at Day 15
Measure: Percentage of participants who achieve clinical response Time: 15 daysDescription: To demonstrate in patients receiving standard of care that the percentage with viral clearance at Day 15 with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo
Measure: Percentage of Participants with Viral Clearance Time: 15 DaysDescription: To assess in patients receiving standard of care the safety of hydroxychloroquine or hydroxychloroquine and azithromycin compared to placebo
Measure: Number of participants receiving hydroxychloroquine or hydroxychloroquine and azithromycin with adverse events of hydroxychloroquin or hydroxychloroquine and azithromycin compared to placebo Time: 40 daysThe objective of this study is to develop and evaluate an algorithm which accurately predicts mortality in COVID-19, pneumonia and mechanically ventilated ICU patients.
Description: Deceased or not deceased
Measure: Mortality outcome in COVID-19 ICU patients Time: Through study completion, an average of 2 monthsDescription: Deceased or not deceased
Measure: Mortality outcome in mechanically ventilated ICU patients Time: Through study completion, an average of 2 monthsDescription: Deceased or not deceased
Measure: Mortality outcome in pneumonia ICU patients Time: Through study completion, an average of 2 monthsThe search for novel therapies to address the ongoing coronavirus (COVID-19) pandemic is ongoing. No proven therapies have been identified to prevent progression of the virus. Preliminary data suggest that inhaled nitric oxide (iNO) could have benefit in preventing viral progression and reducing reliance on supplemental oxygen and ventilator support. Expanded access allows for iNO to be delivered via the portable INOpulse delivery system for the treatment of COVID-19.
Retrospective study on the efficacy of baricitinib in 12 COVID-19 patients with moderate pneumonia.
Description: All adverse event recording
Measure: To assess the safety of baricitinib combined with antiviral (lopinavir-ritonavir) in terms of serious or non-serious adverse events incidence rate. Time: 2 weeksDescription: The percentage of patients improving the clinical and respiratory parameters compared with controls.
Measure: To evaluate the impact of baricitinib in terms of clinical, laboratory, respiratory parameters. Time: 2 weeksDescription: The percentage of ICU admission in baricitinib group as compared with controls.
Measure: ICU admission rate Time: 2 weeksDescription: The percentage of discharged in baricitinib group as compared with controls.
Measure: Discharge rate. Time: 2 weeksFor limiting COVID-19 spreading, the World Health Organisation (WHO) recommended worldwide confinement on 2010. In France, unessential institutions were closed on March 14th and population confinement was decided on March 17th. Quarantine and/or confinement could lead to psychological effects such as confusion, suicide ideation, post-traumatic stress symptoms or anger COVID-19 outbreak highlighted a considerable proportion of health care workers (HCW) with depression, insomnia, anxiety and distress symptoms. In front line, facing the virus with the fear of contracting it and contaminate their closest. During previous outbreaks (H1N1, SARS), HCWs have been shown to experience such negative psychological effects of confinement as well as work avoidance behaviour and physical interaction reduction with infected patients (4-7). In France, Covid 19 outbeak led to increase ICU bed capacity with a full reorganization of the human resources. Some caregivers were reassigned to newly setup units admitting or not Covid-19 patients. In the same time, non-caregivers were also encouraged to work at home whenever possible. Thus, every hospital staff member's private and professional life could be altered by the Covid-19 outbreak. As all these changes in the daily life could induce psychological disturbances, the present study was aimed at assessing the acute anxiety level (main objective) of the staff in our Tertiary University Hospital, (6300 employees). Secondarily, the self-reported insomnia, pain, catastrophism and work avoidance behaviour levels were assessed
Description: Mesured by STAY Scale
Measure: Anxiety Time: 15 to 45 days after the beginning of the outbreakDescription: Participant suffering of Insomnia
Measure: Insomnia Time: 15 to 45 days after the beginning of the outbreakDescription: Participant suffering of catastrophism
Measure: Catastrophism Time: 15 to 45 days after the beginning of the outbreakIn early December 2019, cases of pneumonia of unknown origin were identified in Wuhan, China. The causative virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of international concern. According to the World Health Organization (WHO), the management of COVID-19 has focused primarily on infection prevention, detection and patient monitoring. However, there is no vaccine or specific treatment for SARS-CoV-2 due to the lack of evidence. Treatment options currently include broad-spectrum antiviral drugs but the efficacy and safety of these drugs is still unknown. Convalescent plasma has previously been used to treat various outbreaks of other respiratory infections; however, it has not been shown to be effective in all the diseases studied. Therefore, clinical trials are required to demonstrate its safety and efficacy in patients with VIDOC-19. The present work seeks to determine the mortality from any cause up to 14 days after plasma randomization of patients cured of COVID-19 compared to the Best Available Therapy in subjects with SARS-CoV-2 pneumonia. This is a 2:1 randomized, double-blind, single-center, phase 2, controlled clinical trial (plasma: best available therapy) for the treatment of SARS-CoV-2 pneumonia.
Description: any cause mortality during the first 14 days of treatment
Measure: Early all-cause mortality Time: 14 daysDescription: (48-hour sampling interval from day 3 of hospitalization to two consecutive negatives).
Measure: Time in days for SARS-CoV-2 RT-PCR negatives Time: 90 daysDescription: In subjects of both arms at day 0, 3, 7, 14 and 90.
Measure: The serum anti-SARS-CoV-2 antibody titres Time: 90 daysDescription: Comparison of anti-SARS-CoV-2 antibody titers
Measure: Detection of serum antibodies Time: days 0, 3, 7, 14 and 90.To date, there is no efficient therapeutics to prevent or treat COVID-19 related pulmonary failure. Corticosteroids (CS) could be a helpful therapeutic. Retrospective reports suggested survival improvement in patients with acute respiratory distress syndrome (ARDS). CT scan for COVID19 hospitalized patients showed sometimes unusual aspects of pneumonia, suggestive of an organizing phase of diffuse alveolar damage (DAD). We hypothesize that, in the context of alveolar aggression induced by COVID-19, CT scan could help to individualize patients with a high probability of pulmonary organizing process who could benefit from CS treatment.
Description: The 7-category ordinal scale is as follow: Not hospitalized with resumption of usual activities Not hospitalized, but unable to resume usual activities Hospitalized, not requiring O2 Hospitalized, requiring O2 from 1 to 5 l/min Hospitalized, requiring O2 >6 l/min, nasal high-flow O2, non-invasive mechanical ventilation, or both Hospitalized, requiring ECMO, invasive mechanical ventilation, or both Death.
Measure: Clinical improvement defined by the improvement of 2 points on a 7-category ordinal scale, at 14 days. Time: 14 daysThis is a single arm, prospective, observational, single center study to assess the role of interleukin-6 (IL-6) and soluble interleukin 6 receptor (sIL-6R) as predictors of efficacy and safety outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab. At least 30 patients will be enrolled who are diagnosed with severe COVID-19 pneumonia and meet the entry criteria.
Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab
Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab Time: baselineDescription: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab
Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab Time: 24 hours post treatmentDescription: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab
Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab Time: 48 hours post treatmentDescription: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab
Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab Time: on Day 7Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab
Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab Time: on Day 28Observational pilot single-center study aiming to determine the microbiota of critically ill patients infected with SARS-CoV-2. COVID-19 patients will be compared to historical critically ill controls with no SARS-CoV-2 infection.
Description: relative abundances and diversity indices
Measure: Composition of the fecal bacterial and fungal microbiota Time: At 28 daysDescription: Alterations in fecal microbiota composition (including virose, bacteria and fungi) in COVID-19 patients compared with controls
Measure: Analysis of the faecal microbiota from rectal swab Time: at baseline and every 7 days during 28 daysDescription: Alterations in respiratory microbiota composition (including virose, bacteria and fungi) in COVID-19 patients compared with controls
Measure: Analysis of the respiratory microbiota from the bronchoalveolar lavage liquid Time: at baseline and every 7 days during 28 daysDescription: Changes in blood, c-reactive protein, leucocyte, lymphocyte from baseline
Measure: Serum inflammatory markers changes Time: at 28 days,Description: changes in Cytokine/ chemokine from baseline
Measure: Inflammatory markers changes Time: at 28 days,Description: death
Measure: Mortality Time: at 28 days,Description: Number of days alive without mechanical ventilation
Measure: mechanical ventilation free days Time: at 28 days,COVID-19 originated from Severe Acut Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection leads to critical condition due to hypoxemic respiratory failure with the background of viral pneumonia. Both alevolar recruitment and the subsequent optimal positive end-expiratory pressure (PEEP) adjustment has a pivotal role in the elimination of atelectasis developed by inflammation in the lung parenchyma The gold standard of the follow up of recruitment manoeuvre is the chest computed tomography (CT) examination. However, reduction of intrahospital transport and the exposure with healthcare workers are recommended because of the extremely virulent pathogen spreading easily by droplet infection. In this case bedside investigations have an utmost importance in the management of hygiene regulations. Electric impedance tomography (EIT) is a non-invasive, radiation free functional imaging technique easily applicable at the bedside.
Description: Estimation of change in compliance (ml/cmH2O) from the beginning to end of of the incremental/decremental PEEP alveolar recruitment.
Measure: Changes in lung compliance Time: 20 minutesDescription: Estimation of change in global impedance (%) from the beginning to end of of the incremental/decremental PEEP alveolar recruitment.
Measure: Change in global impedance Time: 20 minutesDescription: Estimation of change in global impedance (%) on a daily manner.
Measure: Change in recruitability Time: 7 daysDescription: Change in arterial partial pressure of oxygen (PaO2) (mmHg) following recruitment
Measure: Gas exchange Time: 20 minutes and 7 daysDescription: Change in plateau pressure (cmH2O) following recruitment
Measure: Plateau pressure Time: 20 minutes and 7 daysDescription: Change in end expiratory lung impedance (%)
Measure: End expiratory lung impedance (EELI) Time: 20 minutes and 7 daysDescription: Change in antero-to-posterior ventilation ratio (%) following intervention
Measure: Antero-to-posterior ventilation ratio Time: 20 minutes and 7 daysDescription: Change in center of ventilation (%) following intervention
Measure: Center of ventilation Time: 20 minutes and 7 daysDescription: Change in global inhomogeneity index (%) following intervention
Measure: Global inhomogeneity index Time: 20 minutes and 7 daysThis trial will determine the safety and estimate efficacy of targeted corticosteroids in mechanically ventilated patients with the hyper-inflammatory sub phenotype of ARDS due to coronavirus disease 2019 (COVID-19) by implementing a Phase 2A clinical trial.
Description: Total number of ventilator free days to day 28 of hospitalization. If a patient dies prior to day 28, they will be counted as zero ventilator free days. Follow up will be performed via phone or electronically to determine ventilator free status of those patients discharged prior to day 28.
Measure: Ventilator Free Days (VFD) at Day 28 Time: 28 DaysDescription: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.
Measure: Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale. Time: 14 DaysNovel coronavirus COVID-19 has become a health emergency around the world. Since first patients were detected in Wuhan China, in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. These immunomodulatory properties of MSCs support performance of the phase I/II, placebo- controlled, randomized MSCs for treatment of severe COVID-19 pneumonia.
Description: Index of therapy success to preserve Intensive Care Hospitalization space
Measure: Proportion of patients who have achieved withdrawal of invasive mechanical ventilation Time: 0-7 daysDescription: To measure global success
Measure: Rate of mortality Time: 28 daysDescription: Index based in the 4 most relevant symptoms and signs: fever, shortness of bread, %Hemoglobin Saturation and PaO2 / FiO2
Measure: Proportion of patients who have achieved clinical response Time: 0-7daysDescription: Evaluation of pneumonia changes
Measure: Proportion of patients who have achieved radiological responses Time: 0-28 daysDescription: Haemogram and cell subpopulations
Measure: Blood white cell counts and their subpopulations. Time: 0-180 daysDescription: Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs
Measure: Cellular markers of inflammation Time: 0-180 daysDescription: IL-10, IL-6, IP-10, TNF-alpha
Measure: Cytokines and chemokines in peripheral blood Time: 0-180 daysThe aim of the research is to improve patient management by rapidly identifying, based on the terrain and clinical and biological characteristics, those patients likely to present a severe form of ARDS at risk of leading to intensive care
This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab plus standard-of-care (SOC) compared with placebo plus SOC in adult patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS).
Description: Clinical response is defined as survival without ever requiring invasive mechanical ventilation from Day 3 to Day 29 (both inclusive). A patient will be defined as a non-responder if the worst clinical status at any time from Day 3 to Day 29 is score 6, 7 or 8 on a 9-point ordinal scale ranging from 0 up to 8. Scores 6, 7 and 8 in the 9-point ordinal scale are defined as follows: Hospitalized patients with severe disease have score 6 if they need intubation and mechanical ventilation and score 7 if they need ventilation + additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation). Patients who die have score 8.
Measure: Number of patients with clinical response Time: Day 3 to Day 29Description: COVID-19-related death during the 4-week period after study treatment.
Measure: COVID-19-related death rate during the 4-week period after study treatment Time: 4 weeksDescription: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the C-reactive protein (CRP) Time: Baseline, Day 29Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the serum ferritin Time: Baseline, Day 29Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the D-dimer Time: Baseline, Day 29Description: Safety will be monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).
Measure: Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs Time: 127 daysThe global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide.1 As of April 14, 2020, there have been more than 1.5 million reported cases and 124 000 deaths in more than 200 countries. A recent open-label nonrandomized French study reporte that addition of azithromycin to hydroxychloroquine in 6 patients resulted in numerically superior viral clearance (6/6, 100%) compared with hydroxychloroquine monotherapy (8/14, 57%) or control (2/16, 12.5%). Azithromycin alone has never been tested, whereas azithromycin has immunomodulating and anti-inflammatory properties that could theoretically prevent or limit secondary worsening. Our hypothesis is that azithromycin combined with amoxicillin/clavulanate will be superior to amoxicillin/clavulanate alone to obtain viral clearance at Day 6 in COVID-19 patients with pneumonia and hospitalized in a non-intensive care unit ward.
Description: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample
Measure: Rate of positive SARS-CoV-2 RT-PCR Time: Day 6Description: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample
Measure: Rate of positive SARS-CoV-2 RT-PCR Time: Day 10Description: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 score. Scale ranging from 0 to 8 (0:unifected; 8:dead)
Measure: Clinical evolution on the World Health Organization Ordinal Scale for Clinical Improvement for COVID-19 Time: day 6, day 10, and day 30Description: Total duration of antibiotic treatment during the 30 days following inclusion
Measure: Total duration of antibiotic treatment during the 30 days following inclusion Time: 30 daysDescription: Number of all-cause mortality during the 30 days following inclusion
Measure: Number of all-cause mortality during the 30 days following inclusion Time: 30 daysDescription: Number of in-hospital mortality during the 30 days following inclusion
Measure: Number of in-hospital mortality during the 30 days following inclusion Time: 30 daysDescription: Number of patients transferred to intensive care unit during the 30-day follow-up
Measure: Number of patients transferred to intensive care unit during the 30-day follow-up Time: 30 daysDescription: Number of days without mechanical ventilation during the 30 days following inclusion
Measure: Number of days without mechanical ventilation during the 30 days following inclusion Time: 30 daysDescription: adverse events attributable to antibiotic treatment during the 30 days following inclusion
Measure: adverse events attributable to antibiotic treatment during the 30 days following inclusion Time: 30 daysDescription: Hospital length of stay during the 30 days following inclusion
Measure: Hospital length of stay during the 30 days following inclusion Time: 30 daysCovid-19 infection is an on-going pandemic with worse diagnosis in adults with comorbid conditions such as hypertension and cardiopulmonary diseases. Obstructive sleep apnea (OSA) is common in those comorbidities and may contribute to worse prognosis for the Covid-19 cases.
Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale
Measure: The rate of clinical improvement Time: 28 daysDescription: Time to hospital discharge, ICU discharge, weaning from intubation, weaning from supplemental oxygen, incident pneumonia, ARDS, in-hospital mortality
Measure: Clinical status Time: 7, 14, 21, 28 daysDescription: Re-analysis of the correlation of obstructive sleep apnea (objectively verified) severity in terms of apnea-hypopnea index and oxygenation levels with the primary and secondary outcomes as described above (the rate of clinical improvement defined as a decline of 2 categories from admission on a 7-category ordinal scale; time to hospital discharge, ICU discharge, weaning from intubation, weaning from supplemental oxygen, incident pneumonia, ARDS, in-hospital mortality as well as with the lung function, CO-diffusion capacity, cardiac function, CT thorax pathologies, biomarkers (cytokines, polymorphisms) and IgG-antibodies after 4 months.
Measure: Long-term outcomes Time: 4 months after the initial hospital admissionThis study will assess the pharmacodynamics, pharmacokinetics, safety and efficacy of two different doses of tocilizumab (TCZ) in combination with standard-of-care (SOC) in hospitalized adult participants with moderate to severe COVID-19 pneumonia.
The purpose of the study is to confirm if BACTEK-R (MV130) provides clinical benefit in subject with mild pneumonia (CURB-65≤2) by COVID-19 admitted to the Hospital.
Description: Number of subjects presenting a improvement in their clinical condition from day 1 to 14 that lead their hospital discharged. Based on the measure of the secondary outcomes.
Measure: Clinical recovery Time: 2 weeksDescription: Number of subjects presenting a worsening in their clinical condition from day 1 to 14 that leads to their admission to the intensive care unit or their death. Based on the measure of the secondary outcomes.
Measure: Clinical worsening Time: 2 weeksDescription: Symptom (fever, cough, dyspnea, myalgia, diarrhea and so on) will be daily record and classified as mild, moderate, severe.
Measure: Clinical severity Time: 2 weeksDescription: Time of reduction or disappearance of the symptoms
Measure: Time to symptoms remission Time: 2 weeksDescription: Record of all the medication administered to the subject
Measure: Medication Use Time: 2 weeksDescription: Time from the subject's admission to the coronavirus unit until discharge
Measure: Hospitalization time Time: 2 weeksDescription: Blood routine test will be carried out days 1 and 7
Measure: Blood routine test Time: Days 1 and 7Description: Heart rate will be followed everyday during time frame
Measure: Heart rate Time: 2 weeksDescription: Blood pressure will be followed everyday during time frame
Measure: Blood pressure Time: 2 weeksDescription: Cardiac auscultation will be recorded everyday during time frame
Measure: Cardiac auscultation Time: 2 weeksDescription: Blood oxygen saturation will be followed everyday during time frame
Measure: Oxygen saturation Time: 2 weeksDescription: Adverse events during treatment
Measure: Adverse events Time: 2 weeksThis study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in hospitalized patients with moderate COVID-19 disease.
Description: Number and severity of adverse events
Measure: Phase 1: Frequency and Severity of Adverse Events (AE) Time: Up to 12 monthsDescription: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR
Measure: Phase 1: Rate of clearance of SARS-CoV-2 Time: Up to 12 monthsDescription: Proportion of subjects who improved clinical symptoms related to lower respiratory tract infection, as measured by National Early Warning Score 2 (NEWS2) score or radiologic evaluation as measured by protocol-defined radiologic evaluation score.
Measure: Phase 1: Rate of clinical improvement Time: Up to 12 monthsDescription: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR in nasal and/or lower respiratory tract samples. Negative results will need to be confirmed by a second negative result in the same sample type at least 24 hours after the first negative result.
Measure: Phase 2: Time to Clearance of SARS-CoV-2 Time: Up to 28 daysDescription: Time from the date of randomization to the first date of improved clinical symptoms related to lower respiratory tract infection. Improvement as measured by National Early Warning Score 2 (NEWS2) Score.
Measure: Phase 2: Time to Clinical Improvement by NEWS2 Score Time: Up to 28 daysDescription: Time from the date of randomization to the first date of improved clinical symptoms related to lower respiratory tract infection. Improvement as measured by Radiologic Evaluation Score.
Measure: Phase 2: Time to Clinical Improvement by radiologic evaluation score Time: Up to 28 daysDescription: Number and severity of adverse events
Measure: Phase 2: Frequency and Severity of Adverse Events (AE) Time: up to 12 monthsDescription: Time to medical discharge as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by time to medical discharge Time: up to 12 monthsDescription: Hospital utilization will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by hospital utilization Time: up to 12 monthsDescription: Mortality rate will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by measuring mortality rate Time: up to 12 monthsDescription: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.
Measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score Time: Up to 28 daysDescription: Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).
Measure: Time to Pulmonary Clearance Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of cough
Measure: Rate of Clinical Improvement of cough Time: Up to 28 daysDescription: For ventilatory support subjects, the days with supplemental oxygen-free.
Measure: Supplemental oxygen-free days Time: Up to 28 daysDescription: Proportion of subjects who need invasive or non-invasive ventilation
Measure: Proportion of subjects requiring ventilation Time: Up to 28 daysDescription: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR
Measure: Rate of Clearance of SARS-CoV-2 Time: Up to 12 monthsCOVID-19 has a high infection rate and mortality, and serious complications such as heart injury cannot be ignored. Cardiac dysfunction occurred in COVID-19 patients, but the law and mechanism of cardiac dysfunction remains unclear. The occurrence of progressive inflammatory factor storm and coagulation dysfunction in severe and fatal cases of NCP points out a new direction for reducing the incidence of severe and critically ill patients, shortening the length of duration in severe and critically ill patients and reducing the incidence of complications of cardiovascular diseases. Aspirin has the triple effects of inhibiting virus replication, anticoagulant and anti-inflammatory, but it has not received attention in the treatment and prevention of NCP. Although Aspirin is not commonly used in the guidelines for the treatment of NCP, it was widely used in the treatment and prevention of a variety of human diseases after its first synthesis in 1898. Subsequently, aspirin has been confirmed to have antiviral effect on multiple levels. Moreover, one study has confirmed that aspirin can inhibit virus replication by inhibiting prostaglandin E2 (PGE2) in macrophages and upregulation of type I interferon production. Subsequently, pharmacological studies have found that aspirin as an anti-inflammatory and analgesic drug by inhibiting cox-oxidase (COX). Under certain conditions, the platelet is the main contributor of innate immune response, studies have found that in the lung injury model in dynamic neutrophil and platelet aggregation. In summary, the early use of aspirin in covid-19 patients, which has the effects of inhibiting virus replication, anti-platelet aggregation, anti-inflammatory and anti-lung injury, is expected to reduce the incidence of severe and critical patients, shorten the length of hospital duration and reduce the incidence of cardiovascular complications.
Description: TTCR is defined as the study treatment (oral aspirin enteric-coated tablet) began to fever, breathing rate, blood oxygen saturation recovery, and cough relieving for at least 72 hours.
Measure: clinical recovery time (TTCR) Time: not more than 14 daysDescription: Time of SARS-CoV2 in upper respiratory tract specimens overcasting detected by RT-PCR.
Measure: the time of SARS-CoV2 overcasting Time: not more than 37 daysItaly was the first European country affected by a severe outbreak of the Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic emerged from Wuhan region (China), with a high morbidity and mortality associated with the disease. In light of its pandemic spread and the very limited therapeutic options, COronaVIrus Disease 19 (COVID-19) is considered an unprecedented global health challenge. Therefore, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research. This is an interventional, non-pharmacological, open, randomized, prospective, non-profit study on the adjuvant use of oxygen ozone therapy plus probiotic supplementation in the early control of disease progression in patients with COVID-19. Contextually, all patients are treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of an ozone therapy-based intervention (accompanied by supplementation with probiotics) in containing the progression of COVID-19 and in preventing the need for hospitalization in intensive care units.
Description: Comparison between the two groups
Measure: Delta in the number of patients requiring orotracheal intubation despite treatment Time: 21 daysDescription: Comparison between the two groups
Measure: Delta of crude mortality Time: 21 daysDescription: Comparison between the two groups
Measure: Delta of length of stay for patients in hospital Time: 90 daysDescription: Comparison between the two groups
Measure: delta in the value of interleukin (IL)-1 Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of IL-6 Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of IL-10 Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of Tumor Necrosis Factor (TNF)-alpha Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR) Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of CD8+ CD38/ HLA-DR Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of fecal calprotectin Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of lipopolysaccharide (LPS) Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of zonulin Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of alpha1-antitrypsin Time: 21 daysThis phase I/II trial studies low-dose radiation therapy as a focal anti-inflammatory treatment for patients with pneumonia or SARS associated with COVID-19 infection.
Description: The rate will be reported, along with a two-sided 95% exact binomial confidence interval, using the Clopper-Pearson method. The observed extubation rate will be compared to the null rate of 20% using a two-sided binomial test. Statistical significance is assessed at the 0.05 level.
Measure: Rate of extubation (for intubated patients) Time: Screening up to 28 days after radiation therapyDescription: Temperature in degrees (F)
Measure: Clinical outcome - Temperature Time: Screening up to 28 days after radiation therapyDescription: Heart rate in beats per minutes
Measure: Clinical outcome - Heart Rate Time: Screening up to 28 days after radiation therapyDescription: Systolic blood pressure in mm Hg
Measure: Clinical outcome - Systolic blood pressure Time: Screening up to 28 days after radiation therapyDescription: Oxygen saturation in percentage
Measure: Clinical outcome - Oxygenation Time: Screening up to 28 days after radiation therapyDescription: Respiratory rate in breaths per minute
Measure: Clinical outcome - Respirations Time: Screening up to 28 days after radiation therapyDescription: FI02 in percentage
Measure: Clinical outcome - FiO2 Time: Screening up to 28 days after radiation therapyDescription: Positive end expiratory pressure (PEEP) in cm H20
Measure: Clinical outcome - PEEP Time: Screening up to 28 days after radiation therapyDescription: Tidal volume in mL
Measure: Clinical outcome - Tidal volume Time: Screening up to 28 days after radiation therapyDescription: Extubation/intubation events in percentage
Measure: Clinical outcome - Intubation/Extubation events Time: Screening up to 28 days after radiation therapyDescription: Survival in percentage
Measure: Clinical outcome - Overall survival Time: Screening up to 28 days after radiation therapyDescription: Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS.
Measure: Radiographic outcome - Chest xray Time: Screening up to 28 days after radiation therapyDescription: CT scans with volume of consolidation measured in cubic centimeters.
Measure: Radiographic outcome - CT can Time: Screening up to 28 days after radiation therapyDescription: White blood cell count in cell count x 10^3/mcL
Measure: Serologic outcome - WBC Time: Screening up to 28 days after radiation therapyDescription: Hemoglobin in gm/dL
Measure: Serologic outcome - Hgb Time: Screening up to 28 days after radiation therapyDescription: Procalcitonin in ng/mL
Measure: Serologic outcome - Procalcitonin Time: Screening up to 28 days after radiation therapyDescription: Absolute neutrophil count in cell count x 10^3/mcL
Measure: Serologic outcome - ANC Time: Screening up to 28 days after radiation therapyDescription: Creatine kinase in units/L
Measure: Serologic outcome - Creatine kinase Time: Screening up to 28 days after radiation therapyDescription: Myoglobin in ng/mL
Measure: Serologic outcome - Myoglobin Time: Screening up to 28 days after radiation therapyDescription: Albumin in gm/dL
Measure: Serologic outcome - Albumin Time: Screening up to 28 days after radiation therapyDescription: Coagulation pathway time in seconds
Measure: Serologic outcome - PT/PTT Time: Screening up to 28 days after radiation therapyDescription: D-Dimer in ng/mL
Measure: Serologic outcome - D-Dimer Time: Screening up to 28 days after radiation therapyDescription: Gamma-glutamyl transferase in units/L
Measure: Serologic outcome - GGT Time: Screening up to 28 days after radiation therapyDescription: Trygliciericdes in mg/dL
Measure: Serologic outcome -Triglycerides Time: Screening up to 28 days after radiation therapyDescription: Ferritin in ng/mL
Measure: Serologic outcome -Ferritin Time: Screening up to 28 days after radiation therapyDescription: Fibrinogen in mg/dL
Measure: Serologic outcome -Fibrinogen Time: Screening up to 28 days after radiation therapyDescription: Immune marker flow cytometry (refractive index)
Measure: Serologic Immune markers flow cytometry Time: Screening up to 28 days after radiation therapyDescription: Bilirubin in mg/dL
Measure: Serologic outcome -Bilirubin Time: Screening up to 28 days after radiation therapyDescription: Lactate Dehydrogenase in units/L
Measure: Serologic outcome - LDH Time: Screening up to 28 days after radiation therapyDescription: Creatinine in mg/dL
Measure: Serologic outcome - Creatinine Time: Screening up to 28 days after radiation therapyDescription: Estimated Glomerular Filtration Rate in mL/min/m2
Measure: Serologic outcome - EGFR Time: Screening up to 28 days after radiation therapyDescription: C-Reactive Protein in mg/L
Measure: Serologic outcome - CRP Time: Screening up to 28 days after radiation therapyDescription: Alanine Aminotransferase in units/L
Measure: Serologic outcome - ALT Time: Screening up to 28 days after radiation therapyDescription: Asparatate Aminotransferase in units/L
Measure: Serologic outcome - AST Time: Screening up to 28 days after radiation therapyDescription: Troponin-I in ng/mL
Measure: Serologic outcome - Troponin-I Time: Screening up to 28 days after radiation therapyDescription: B-Natriuretic Peptid in pg/mL
Measure: Serologic outcome - BNP Time: Screening up to 28 days after radiation therapyDescription: pH (no unit)
Measure: Serologic outcome - Blood Gases pH Time: Screening up to 28 days after radiation therapyDescription: pressure of O2 in mm Hg
Measure: Serologic outcome - Blood Gases pO2 Time: Screening up to 28 days after radiation therapyDescription: pressure of CO2 in mm Hg
Measure: Serologic outcome - Blood Gases pCO2 Time: Screening up to 28 days after radiation therapyDescription: Lactic Acid in mmol/L
Measure: Serologic outcome - Lactic Acid Time: Screening up to 28 days after radiation therapyDescription: Interleukin-6 in pg/mL
Measure: Serologic outcome - IL-6 Time: Screening up to 28 days after radiation therapyDescription: Potassium in mmol/L
Measure: Serologic outcome - Potassium Time: Screening up to 28 days after radiation therapyIn light of its high morbidity and mortality, COronaVIrus Disease 19 (COVID-19) pandemic spread is considered an unprecedented global health challenge. Given the very limited therapeutic options available against Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic at this time, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research. This is an observational, retrospective, non-profit study on the adjuvant use of bacteriotherapy in the early control of disease progression in patients affected by COVID-19 and treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of bacteriotherapy in reducing the clinical impact of acute diarrhea, containing the progression of COVID-19 and preventing the need for hospitalization in intensive care units.
Description: Comparison between the two groups. Acute diarrhea was defined as a stool with increased water content, volume, or frequency that lasts less than 14 days.
Measure: delta of time of disappearance of acute diarrhea Time: 21 daysDescription: Comparison between the two groups
Measure: Delta in the number of patients requiring orotracheal intubation despite treatment Time: 21 daysDescription: Comparison between the two groups
Measure: Delta of crude mortality Time: 21 daysDescription: Comparison between the two groups
Measure: Delta of length of stay for patients in hospital Time: 21 daysThis is a compassionate use, proof of concept, phase IIb, prospective, interventional, pilot study in which the investigators will evaluate the effects of compassionate-use treatment with IV tirofiban 25 mcg/kg, associated with acetylsalicylic acid IV, clopidogrel PO and fondaparinux 2.5 mg s/c, in patients affected by severe respiratory failure in Covid-19 associated pneumonia who underwent treatment with continuous positive airway pressure (CPAP).
Description: Change in ratio between partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, and inspired oxygen fraction at baseline and after study treatment
Measure: P/F ratio Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Change in partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: PaO2 difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Change in alveolar-arterial gradient of oxygen at baseline and after study treatment. Arterial alveolar gradient will be calculated using the following parameters derived from arterial blood gas analysis: partial pressure of oxygen in arterial blood and partial pressure of carbon dioxide in arterial blood.
Measure: A-a O2 difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Number of days on continuous positive end expiratory pressure (CPAP)
Measure: CPAP duration Time: From the first day of study drugs administration (T0) until day 7 post study drugs administrationDescription: Difference in intensity of the respiratory support (non invasive mechanical ventilation, CPAP, high flow nasal cannula (HFNC), Venturi Mask, nasal cannula, from higher to lower intensity, respectively) employed at baseline and at 72 and 168 hours after study treatment initiation
Measure: In-hospital change in intensity of the respiratory support Time: At baseline and 72 and 168 hours after treatment initiationDescription: Difference in partial pressure of carbon dioxide in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: PaCO2 difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in concentration of bicarbonate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: HCO3- difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in concentration of lactate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: Lactate difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in hemoglobin concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.
Measure: Hb difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in platelet concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.
Measure: Plt difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Any major or minor adverse effect occuring during and after the administration of the study drug (e.g. bleeding)
Measure: Adverse effects Time: From the first day of study drugs administration until day 30 post study drugs administrationThis study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab administered in adult patients with Coronavirus Disease 2019 (COVID-19) severe pneumonia, acute lung injury, or acute respiratory distress syndrome. Patients will be randomly assigned to receive ravulizumab in addition to best supportive care (BSC) (2/3 of the patients) or BSC alone (1/3 of the patients). Best supportive care will consist of medical treatment and/or medical interventions per routine hospital practice.
This is a multicenter, randomized, controlled, open-label clinical trial testing the use of ozone auto-hemotherapy in hospitalized patients with Covid-19 pneumonia. Eligible patients will be randomly assigned to receive either ozone auto-hemotherapy plus standard treatment, or standard treatment alone. Patients in the ozone auto-hemotherapy group will receive treatment mixing 100-200ml of blood with ozone at a concentration of 40 μg / mL with a gas volume of 200 ml. Treatment will occur every 12h during 5 days. Standard treatment will be the one used in each hospital participating in the trial. All analyses will be done according to the intention-to-treat principle
Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)
Measure: Rate of patients achieving improvement in clinical condition at day 14 after recruitment Time: 14 daysDescription: mortality
Measure: Mortality at day 28 Time: 28 daysDescription: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)
Measure: Rate of patients achieving improvement in clinical condition at day 28 after recruitment Time: 28 daysDescription: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)
Measure: Rate of patients achieving improvement in clinical condition at day 7 after recruitment Time: 7 daysDescription: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)
Measure: Time to clinical improvement or hospital discharge Time: 28 daysDescription: Ventilator-free days from last extubation day until day 28 after recruitment
Measure: Number of ventilator-free days at 28 days Time: 28 daysDescription: Days hospitalized
Measure: Hospital length of stay Time: 28 daysDescription: Number of days until a 2-fold decrease in ferritin (ng/mL)
Measure: Time to a 2-fold decrease in ferritin Time: 14 daysDescription: Number of days until a 2-fold decrease in C-Protein Reactive (mg/L)
Measure: Time to a 2-fold decrease in C-protein reactive Time: 14 daysDescription: Number of days until a 2-fold decrease in Dimer-D (ng/mL)
Measure: Time to a 2-fold decrease in Dimer-D Time: 14 daysDescription: Number of days until a 2-fold decrease in Lactate Dehydrogenase (U/L)
Measure: Time to a 2-fold decrease in Lactate Dehydrogenase Time: 14 daysDescription: Number of days until a 2-fold decrease in Neutrophils to Lymphocytes ratio
Measure: Time to a 2-fold decrease in Neutrophils to Lymphocytes ratio Time: 14 daysIs Lung Ultrasound really useful in diagnosing COVID19? What can be the usefulness of the Lung Ultrasound in the COVID19 epidemic? In the current state of the art, Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of Lung Ultrasound in the diagnosis of COVID-19 are not yet known. Alveolar-interstitial lung diseases such as viral pneumonia and ARDS seems to have a specific ultrasound pattern that distinguishes them from bacterial pneumonia, preferentially represented by B lines, morphological irregularity of the pleural line, and small subpleural consolidations, but they could share these patterns with other pathologies, reducing specificity. In Italy, the Lung Ultrasound represents a consolidated method for the evaluation and management of all patients who come to the ER, and what we are sure of is its high sensitivity in identifying pathological patterns. Our preliminary data suggest that Lung Ultrasound is highly reliable not to include but to exclude the diagnosis of COVID-19 in patients with respiratory symptoms.
Description: Lung Ultrasound accuracy in rule-out of patients with respiratory symptoms (fever and / or cough and / or dyspnoea) during the SARS-CoV-2 epidemic compared to nasopharyngeal swab and a composite reference standards
Measure: Negative Predictive Value of Lung Ultrasound in the diagnosis of COVID-19 Time: 30 daysDescription: Lung Ultrasound accuracy in rule-in of patients with respiratory symptoms (fever and / or cough and / or dyspnoea) during the SARS-CoV-2 epidemic compared to nasopharyngeal swab and a composite reference standards
Measure: Positive Predictive Value of Lung Ultrasound in the diagnosis of COVID-19 Time: 30 daysThis phase II expanded access trial studies how well tocilizumab works in reducing the serious symptoms including pneumonitis (severe acute respiratory distress), and preventing future complications in patients with cancer and COVID-19. COVID-19 is caused by the SARS-CoV-2 virus. COVID-19 can be associated with a response by the immune system which may also cause symptoms of COVID-19 to worsen. This inflammation may be called "cytokine storm," which can cause widespread problems in the body. Tocilizumab is a medicine designed to block the action of a protein called interleukin-6 (IL-6) that is involved with the immune system and is known to be a key factor for problems with the immune system attacking the body. Tocilizumab is effective in treating "cytokine storm" from a type of cancer immunotherapy and may be effective in reducing the inflammatory response and "cytokine storm" seen in severe COVID-19 disease. Treating the inflammation may help to reduce symptoms, improve the ability to breath without a breathing machine (ventilator), and prevent patients from having more complications.
The outbreak of coronavirus disease 2019 (COVID-19) at the end of 2019 has seen numerous patients experiencing severe acute lung injury (ALI), which developed into severe respiratory distress syndrome (ARDS). The mortality was as high as 20% -40%. Due to the lack of effective antiviral treatments, supporting treatment is the predominant therapy for COVID-19 pneumonia. Its cure is essentially dependent on the patient's immunity. While the immune system eliminates the virus, numerous inflammatory cytokines are produced and a cytokine storm occurs in severe cases. Mesenchymal stem cells (MSCs) play an important role in injury repair and immune regulation, showing advantageous prospects in the treatment of COVID-19 pneumonia. MSCs prevent cytokine storms by retarding the TNF-α pathway, alleviate sepsis by modulating macrophages, neutrophils, NK cells, DC cells, T lymphocytes and B lymphocytes. After infused, MSCs aggregate in the lungs, improve the lung microenvironment, protect alveolar epithelia, and improve pulmonary fibrosis and pulmonary function.
Description: Improvement of pulmonary function
Measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test Time: 12 monthsDescription: Cytokines level
Measure: Detection of TNF-α levels, IL-10 levels Time: 1,3,6,12monthsDescription: Immunological status
Measure: Detection of immune cells that secret cytokines, including CXCR3+, CD4+, CD8+, NK+ cells, and regulatory T cells (CD4 + CD25 + FOXP3 + Treg cells). Time: 1,3,6,12monthsDescription: Improvement of pulmonary function
Measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test Time: 1,3,6monthsDescription: Infection biomarkers
Measure: Changes of c-reactive protein and calcitonin Time: 1,3,6,12monthsThe outbreak of the coronavirus disease 2019 (COVID-19), first merged in China in December 2019, is now becoming a Public Health Emergency, recently confirmed as a pandemic disease by the World Health Organization. In particular, since February 2020, a rapidly growing number of cases has been identified in Italy. The clinical picture of ranges from asymptomatic cases, mild upper respiratory tract infections to severe pneumonia with respiratory failure and death. In most severe cases, COVID-19 disease may be complicated by acute respiratory distress syndrome (ARDS), septic shock and multiorgan failure. It results fundamental to early identify those subjects who rapidly may worsen their clinical status, often requiring an intensive care unit (ICU) admission. It has been showed that, mainly in more severe forms of SARS-Cov-2 disease, there is the development of an hyperinflammatory status resembling a cytokine storm syndrome, as already reported in SARS patients. A recent study by Haung et al. reported that patients with COVID-19 infection showed high amounts of IL1B, IFN-gamma, IP10 and MCP1, probably linked to activated T-helper1 (Th1) cell responses. Those requiring ICU admission had higher levels of cytokines than those subjects not requiring ICU admission, thus suggesting that cytokine storm was associated with disease severity. A similarity between cytokine profile of COVID-19 disease and secondary haemophagocytic syndrome (sHLH) has been reported. Therefore, it was suggested to screen all patients with severe COVID-19 infection both for hyperinflammatory markers (like ferritin), and the HScore commonly used to generate a probability for diagnosis of sHLH (8), which includes some laboratory parameters like triglycerides, fibrinogen, ferritin, serum aspartate aminostransferase. Based on our experience on patients affected by pneumonia from Covid19, we have observed that those subjects with a more severe prognosis might have some predictive markers. We intend to verify if these markers can identify those subjects with Covid19 infection who need a more intensive therapy and to find a prognosis score.
The aim of this study is to determine the risk factors for development of ventilator-associated pneumonia (VAP) and to identify the prognostic factors of VAP among Coronavirus Disease 2019 (CoViD-19) patients. We hypothesized that CoViD-19 serves as a high risk factor for the development of VAP and it affects clinical outcome measures negatively.
Endothelial injury as a consequence of SARS-CoV-2 infection leads to a dysregulated host inflammatory response and activation of coagulation pathways. Macro- and micro-vascular thrombosis may contribute to morbidity, organ failure, and death. Therapeutic anticoagulation with heparin may improve clinical outcomes in patients with COVID-19 through anti-thrombotic, anti-inflammatory, and anti-viral activities of heparins. This pragmatic, Bayesian adaptive randomized controlled trial will determine whether therapeutic anticoagulation with heparin (subcutaneous low molecular weight heparin or intravenous unfractionated heparin) versus usual care reduces the need for intubation or death in hospitalized patients with COVID-19 not initially requiring invasive mechanical ventilation. The trial uses an adaptive design which was chosen to overcome limitations in available data to inform a priori estimation of event rates and possible effect sizes. The adaptive design also includes response-adaptive randomization based on baseline D-dimer level, probing for differential efficacy across subgroups defined based on initial D-dimer level. This Bayesian adaptive randomized trial will stop at a conclusion 1) when the posterior probability that the proportional odds ratio is greater than 1.0 reaches 99% (definition of benefit); 2) when the posterior probability that the proportional odds ratio is greater than 1.2 is less than 10% (definition of futility) or; 3) when the posterior probability that the proportional odds ratio is less than 1.0 is greater than 90% (definition of harm). The trial will enroll a maximum of 3,000 patients, although in many simulations the trial may require fewer patients. The trial is strategically aligned with the international REMAP-CAP/COVID platform trial to accelerate evidence generation.
Description: The primary endpoint is an ordinal endpoint with three possible outcomes based on the worst status of each patient through day 30: no requirement for invasive mechanical ventilation, invasive mechanical ventilation, or death.
Measure: Intubation and mortality Time: 30 daysDescription: Invasive mechanical ventilation
Measure: Intubation Time: 30 daysDescription: Days alive outside of the hospital through 30 days following randomization
Measure: Hospital-free days Time: 30 daysDescription: Number of days alive outside of the ICU through 30 days following randomization
Measure: ICU-free days Time: 30 daysDescription: Number of days alive without the use of a ventilator through 30 days following randomization.
Measure: Ventilator-free days Time: 30 daysDescription: The use of non-invasive mechanical ventilation or high flow nasal cannula
Measure: Non-invasive ventilation Time: 30 daysDescription: Number of days alive without the use of vasopressors/inotropes and ventilation (including high flow nasal cannula >30 L/min and FIO2 >40%) through 21 days following randomization, ranked with death at anytime during 21 days as -1
Measure: Organ support-free Time: 21 daysDescription: As defined by the International Society on Thrombosis and Haemostasis (ISTH)
Measure: Major bleeding Time: Intervention period (maximum 14 days)Description: Laboratory-confirmed
Measure: Heparin-induced thrombocytopenia (HIT) Time: Intervention period (maximum 14 days)The investigators intend to study the role of early use of methylprednisolone in the hospitalized patients with a diagnosis of COVID-19 pneumonia.
Description: Number of patients transferred to ICU is each of the groups
Measure: Transfer to Intensive care unit (ICU) Time: 14 days followup for every patient in each groupDescription: Number of patients that needed mechanical ventilation in each of the groups
Measure: Need for Mechanical Ventilation Time: 14 days followup for every patient in each groupDescription: Number of patients who died in each of the groups
Measure: Mortality Time: 14 days followup for every patient in each groupDescription: Number of patients who developed ARDS of varying severity per Berlin classification in each of the groups
Measure: Development and Severity of ARDS Time: 14 days followup for every patient in each groupDescription: LOS in each of the groups
Measure: Length of hospital stay (LOS). Time: 14 days followup for every patient in each groupThis is a single arm phase II trial to assess efficacy and confirm safety of infusions of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms,with or without confirmed interstitial COVID-19 pneumonia by chest Xray or CT. A total of 29 eligible subjects will be enrolled to receive anti-SARS-CoV-2 plasma.Outcomes will be compared to hospitalized controls with confirmed COVID-19 disease through retrospective chart review.
Description: Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.
Measure: Transfer to ICU Time: Days 0 - 60Description: Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.
Measure: 28 day mortality Time: Days 0 - 60Description: Will be collected from time of enrollment until completion of the study. The adverse events will be evaluated by CTCAE V5.0 and MedDRA.
Measure: Cumulative incidence of serious adverse events Time: Days 0 - 60Description: Will be done by collecting respiratory tract swabs and testing for SARS-CoV-2 positivity.
Measure: Rates and duration of SARS-CoV-2 Time: Days 0, 7, 14, and 21Description: Serum or plasma will be collected and analyzed for SARS-CoV-2 antibody.
Measure: Serum of plasma antibody titer to SARS-CoV-2 Time: Days 0, 7, 14, and 28Description: Blood will be collected and analyzed for cellular and humoral response.
Measure: Cellular and humoral immune response Time: Days 0, 7, 14, 28Description: All days where a supplemental oxygen is needed will be recorded as a concomitant medication and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the supplemental oxygen free days.
Measure: Supplemental oxygen free days Time: Days 0-28Description: All days where a ventilator is needed will be recorded as a concomitant procedure and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ventilator free days.
Measure: Ventilator free days Time: Days 0 - 28Description: All days where the participant is admitted to the ICU will be recorded and subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ICU free days.
Measure: ICU free days Time: Days 0 - 28Description: The patient will be evaluated throughout their enrollment in the study. The score will be evaluated to see if the score improved or worsened throughout their admission.
Measure: Sequential organ failure assessment score Time: days 0, 1, 4, 7, 14, 21, 28Description: Concomitant medications will be recorded throughout the patients participation in the study and vasopressors will be recorded, if they are needed.
Measure: Need for vasopressors Time: Days 0 - 60Description: Renal function will be assessed throughout the patients participation in the study. If renal replacement therapy is needed, it will be captured as a concomitant procedure.
Measure: Need for renal replacement therapy Time: Days 0 - 60Description: Respiratory function will be assessed throughout the patients participation in the study. If ECMO is needed, it will be captured as a concomitant procedure.
Measure: Need for extracorporeal membrane oxygenation (ECMO) Time: Days 0 - 60Description: Will be calculated from the date the patient entered the hospital until they were discharged.
Measure: Hospital length of stay (LOS) Time: Days 0-60Description: Will be calculated from the date the patient entered the ICU until they were discharged from the ICU.
Measure: ICU LOS Time: days 0 - 60Description: All adverse events will be recorded and evaluated by CTCAE v.5.0. All grade 3 and 4 AEs will be calculated to determine safety of convalescent plasma.
Measure: Grade 3 or 4 Adverse Events (AEs) Time: days 0 - 60Studies performed after coronavirus epidemics (severe acute respiratory syndrome coronavirus, SARS-CoV and Middle East respiratory syndrome coronavirus, MERS-CoV) have shown a long-term impact on respiratory morbidity, musculoskeletal and psycho-social repercussions. Patients with SARS-CoV pneumonia had fibrotic pulmonary sequelae at 45 days (lower DLCO in 27.3% of cases and radiological lesions in 21.5% of cases). In the MERS-CoV pneumonia study, patients had radiological sequelae in 33% of cases and the 12-month evaluation showed persistence of radiological abnormalities in 23.7% of the cases despite an improvement in respiratory function. Clinical presentation and therapeutic management of severe SARS-CoV-2 infection are in part similar to those induced by SARS-CoV and MERS-CoV. Long-term respiratory complications are therefore expected.
Description: Interstitial lung disease diagnosed with a thoracic CT-scan
Measure: medium-term respiratory complications Time: 3 monthsDescription: Interstitial lung disease diagnosed with a thoracic CT-scan
Measure: long-term respiratory complications Time: 12 monthsAcute respiratory distress syndrome (ARDS) is a syndromic definition of an acute lung injury with alteration of biomechanics (lower respiratory system compliance) mostly associated with increased lesional edema. Increase in Pulmonary Vascular Permeability Index (PVPI) accompanied with accumulation of excess Extravascular Lung Water (EVLW) is the hallmark of ARDS. In routine clinical practice, the investigators measure the EVLW and PVPI in ARDS patients, as suggested by expert's recommendations, using a transpulmonary thermodilution (TPTD) technique. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly recognized illness that has spread rapidly throughout Wuhan (Hubei province) to other provinces in China and around the world. Most critically ill patients with SARS-CoV-2 will present the criteria for the definition of ARDS. However, many of these patients have a particular form of ARDS with severe hypoxemia often associated with near normal respiratory system compliance. This combination is almost never seen in severe ARDS. Thus other mechanisms (including probably vascular mechanisms), that are still poorly described, have to be involved in SARS-CoV-2. EVLW and PVPI have never been assessed in SARS-CoV-2 mechanically ventilated patients. The aim of this study is to evaluate these two parameters in order to best characterize and understand the mechanisms related to SARS-CoV-2. Based on observation of several cases in intensive care units (ICU), the investigators hypothesize that there are following different SARS-CoV-2 patterns: 1. Nearly normal compliance, low lung recruitability, normal EVLW and low PVPI. 2. Low compliance due to increased edema, high lung recruitability, high EVLW and high PVPI.
Description: EVLW (ml/kg) measured by a PiCCO device using TPTD thermodilution
Measure: Changes of Extra Vascular Lung Water Time: Since intubation at day 0 and measured repetitively by 6 hours until day 3Description: PVPI measured by a PiCCO device using TPTDventilation, duration of ICU length of stay, ICU mortality
Measure: Changes of Pulmonary Vascular Permeability Index Time: Since intubation at day 0 and measured repetitively by 6 hours until day 3Description: Changes of pulmonary compliance (ml/mmHg)
Measure: Changes of pulmonary compliance Time: Since intubation at day 0 and measured repetitively by 6 hours until day 3Low-dose radiotherapy treatment delivered to both lungs in patients with immune-related pneumonia following COVID-19 infection is backed up by biological and clinical bases that justify its use as a possible therapeutic option in these patients. This is a preliminary exploratory study (non-pharmacological interventional) to evaluate the feasibility and tolerability of low-dose radiotherapy treatment of SARS-Cov-2 immune-mediated pneumonia, for the subsequent implementation of a phase II study.This is a preliminary, monocentric, single-arm, interventional, non-pharmacological exploratory study. All enrolled patients will be treated with low-dose radiotherapy. Participants will undergo irradiation of the lungs, administered in a single fraction at the average prescription dose of 0.7 Gy (further details in the dedicated section).
Description: Evaluation of the feasibility of low-dose radiotherapy treatment of SARS-Cov2 pneumonia, for the purpose of the subsequent implementation of a phase II study; lenght of hospital stay will be recorded
Measure: Lenght of hospital stay (days) Time: Six monthsDescription: Evaluation of the feasibility of low-dose radiotherapy treatment of SARS-Cov2 pneumonia; the number of intensive care unit admissions will be recorded
Measure: Number of Intensive Care Unit admissions Time: Six monthsDescription: Variation of the patient's score according to the Brescia COVID-19 Respiratory Severity Scale (minimum value 0, maximum value 8; higher scores mean a worse outcome) with baseline, assessed at 3, 6 and 10 days after treatment.
Measure: Variation of the Brescia COVID-19 Respiratory Severity Scale after treatment Time: 3, 6 and 10 daysDescription: Evaluation of the safety and tolerance of the low-dose radiotherapy treatment of SARS-Cov2 ( using the CTCAE 5.0 scale)
Measure: Occurence of CTCAE 5.0 adverse events Time: 10 days and 6 monthsDescription: Variation of the radiological findings, assessed by chest X-ray (performed 3 and 6 days after treatment) and defined according to the Brixia scoring system (0-18 scale, with 18 meaning the worse outcome)
Measure: Variation of the chest X-ray radiological findings according to Brixia scoring system Time: 3 and 6 daysHypothesis: low-dose chest computed tomography, has the same accuracy for the diagnosis of pneumonia compared to the routine protocol. In total, 230 patients are planned to be enrolled in the study. Each patient will have 2 studies (routine chest CT and low-dose chest CT) sequentially during one visit to the computed tomography room.
Description: A standardized scale CT1-CT4 will be used. The expected correlation percentage is 90%.
Measure: Evaluate the correlation between standard CT and low-dose CT scans for the detection of community-acquired pneumonia. Time: Upon completion, up to 1 yearDescription: Expected threshold - 10 mm.
Measure: Threshold value of the infiltration zone size detected by low-dose CT scan compared to standard CT scan. Time: Upon completion, up to 1 yearDescription: Expected number - more than two zones.
Measure: Number of infiltration zones of pulmonary parenchyma corresponding to viral pneumonia detected by low-dose CT scan in comparison with standard CT scan. Time: Upon completion, up to 1 yearThis single-center, prospective, open-label, comparator study, blind for central accessor evaluates the efficacy, safety of inhalations of low-doses of melphalan in patients with pneumonia with confirmed or suspected COVID-19. All patients will receive 0,1 mg of melphalan in 7-10 daily inhalations 1 time per day.
Description: The number of patients with the clinical improvement is defined as an improvement of two points (from the status at baseline) on an ordinal scale of clinical improvement on day 28 or discharge from hospital ( whatever occurs earlier) Death Hospitalized with Invasive mechanical ventilation plus additional organ support - ECMO / pressors / RRT Hospitalized with intubation and mechanical ventilation Hospitalized on non-invasive ventilation or high flow oxygen. Hospitalized on a mask or nasal prongs. Hospitalized no oxygen therapy. Ambulatory, with limitation of activities. Ambulatory, no limitation of activities. I. No clinical or virological evidence of infection.
Measure: The changes of COVID Ordinal Outcomes Scale Time: baseline vs Day 14, day 28Description: Percentage of the patients with clinical recovery which is defined as a normalisation of fever, respiratory rate, and oxygen saturation, and improvement of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalization and improvement criteria: Fever - <37°C, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.
Measure: Percentage of the patients with Clinical Recovery Time: baseline vs day 7, day 14, day 28Description: The evaluation of changes in modified Borg dyspnea scale. From 0 to 10 units.A lower score means a better clinical result (0 is the absence of dyspnea, and 10 - is maximal dyspnea). Minimal clinically important difference is 1 unit.
Measure: The changes of the Borg's scale Time: Baseline vs day 7, day 14, day 28Description: Change in C-reactive protein (CRP) level from baseline in mg/ml. A lower level of CRP means a better clinical result.
Measure: CRP level Time: baseline, day 7, Day 14, Day 28Description: Change in blood absolute lymphocyte count from baseline. A higher number of lymphocytes means a better clinical result.
Measure: Lymphocyte count Time: baseline, day 7, Day 14, Day 28Description: Change in blood D-dimer level from baseline. A lower level of D-dimer means a better clinical result.
Measure: D-dimer Time: baseline, day 7, Day 14, Day 28Description: Change in peripheral blood IL-6 level from baseline. A lower level of IL-6 means a better clinical result.
Measure: IL-6 Time: baseline, day 7, Day 14, Day 28Description: Percentage of patients without artificial lung ventilation during the study. A lower percentage of patients means a better clinical result.
Measure: Percentage of patients without artificial lung ventilation Time: baseline, day 7, Day 14, Day 28Randomized open label clinical trial carried out at study centers in Sweden, including Karolinska University Hospital Huddinge, S:t Göran Hospital, Danderyd Hospital and Västmanlands Hospital. Patients with COVID-19 who are hospitalized with oxygen therapy are eligible for inclusion. Subjects are randomized to 14 days of inhalation with ciclesonide 360 µg twice daily or to standard of care. Primary outcome is time (in days) of received supplemental oxygen therapy. Key secondary outcome is a composite outcome of death and received invasive mechanical ventilation within 30 days.
Description: Time (in days) of received supplemental oxygen therapy (defined as being alive and discharged from hospital to home or at least 48 h of not receiving oxygen therapy during hospitalization).
Measure: Duration of received supplemental oxygen therapy Time: 30 days after study inclusionDescription: Rate of and time to (in days) received invasive mechanical ventilation or all-cause death
Measure: Invasive mechanical ventilation or all-cause death Time: 30 days after study inclusionDescription: Rate of and time to (in days) death of any cause
Measure: All cause death Time: 30 days after study inclusionDescription: Rate of and time to (in days) received invasive mechanical ventilation
Measure: Invasive mechanical ventilation Time: 30 days after study inclusionDescription: Maximum received oxygen therapy during hospitalization in liters per minute
Measure: Maximum oxygen therapy Time: 30 days after study inclusionDescription: Time (in days) from study inclusion to discharge from hospital.
Measure: Duration of hospitalization Time: 30 days after study inclusionDescription: Level of remaining dyspnea symptoms according to the Modified Medical Research Council Dyspnea Scale
Measure: Remaining dyspnea symptoms Time: 3 and 6 months after inclusion. (Only for patients hospitalized at S:t Goran's Hospital)Background: On December 2019, a new human coronavirus infection (COVID-19) was detected in China. Its infectivity and virulence characteristics caused a rapid spread, being declared pandemic on March 2020. The mortality attributed to the infection ranges between 3 and 10%. Main risk factors are age, male sex, and chronic degenerative comorbidities. Due to the absence of therapeutic options, potential alternatives such as human immunoglobulin or plasma from convalescent patients have been administered. Due to the severity of the disease and the associated mortality, it is urgent to find therapeutic alternatives. Objective: To assess the safety and efficacy of the administration of Convalescent plasma vs human immunoglobulin in critically ill patients with COVID-19 infection. Material and methods: Randomized Controlled trial of patients diagnosed with respiratory infection by COVID-19, with severe respiratory failure without indication of mechanical ventilation, or those who due to their severity are intubated upon admission. Randomization will be performed 2:1 to receive plasma from convalescent patients or human immunoglobulin. Outcomes: The primary outcome will be time to discharge from hospital for improvement. The safety outcomes will be: Kirby index (PaO2/FiO2) evolution and dead.
Description: Mean days from admission as a suspected case of COVID with hospitalization criteria until discharge
Measure: Mean hospitalization time Time: Through study completion, an average of 3 monthsDescription: Mean of delta of oxigenation index (PaO2/FiO2)
Measure: Mean Oxigenation index evolution Time: Through study completion, an average of 3 monthsDescription: Rate of patients with evolution to severe ARDS (PaO2/FiO2 < 100)
Measure: Rate of severe ARDS Time: Through study completion, an average of 3 monthsDescription: Rate of Dead caused by COVID-19 related complications and time to dead caused by COVID-19 complication
Measure: Rate and time to dead Time: Through study completion, an average of 3 monthsDescription: Mean time with invasive mechanical ventilation
Measure: Mean time with invasive mechanical ventilation Time: Through study completion, an average of 3 monthsDescription: Time to negativization of RT-qPCR SARS-CoV-2 test.
Measure: Time to Viral PCR Negativization Time: Through study completion, an average of 3 months.The purpose of the COVIDNOCHE trial (HFNO versus CPAP Helmet Evaluation in COVID-19 Pneumonia) is to evaluate the comparative effectiveness of standard care non-invasive respiratory support (helmet CPAP versus HFNO) for acute hypoxemic respiratory failure from COVID-19 pneumonia on ventilator-free days (primary outcome) and other clinical outcomes measured up to 90 days.
Description: VFD is the number of days alive and free of mechanical ventilation in the first 28 days after study enrollment. Death before 28 days will be assigned a VFD equal to 0 to penalize non-survival. In cases of repeated intubation and extubation, periods free from invasive ventilation and lasting at least 24 consecutive hours will be calculated and summed. Timing of intubation and extubation will be captured in hours, and the number of hours a patient received invasive ventilation will be used to calculate duration of ventilation.
Measure: Ventilator-Free Days (VFD) Time: 28 daysDescription: Days spent in the ICU and hospital after time of enrollment
Measure: ICU and Hospital Length of Stay Time: 28 daysDescription: Incidence and time to intubation in days after the time of enrollment
Measure: Intubation Time: 28 daysDescription: Incidence of RRT after the time of enrollment
Measure: Renal Replacement Therapy (RRT) Time: 28 daysDescription: Death from any cause during after the time of enrollment
Measure: Mortality Time: 28 days, 90 daysDescription: Changes in Borg Dyspnea Score after time of enrollment
Measure: Dyspnea Time: 1 hourThe study will assess the efficacy and safety of DFV890 for the treatment of SARS-Cov-2 infected patients with COVID-19 pneumonia and impaired respiratory function.
Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.
Measure: APACHE II severity of disease score on Day 15 or on the day of discharge (whichever is earlier) Time: up to Day 15Description: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a log-scale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.
Measure: Serum C-reactive protein (CRP) levels Time: up to Day 29Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Clinical status over time Time: up to Day 29Description: Proportion of participants not requiring mechanical ventilation for survival.
Measure: Proportion of participants not requiring mechanical ventilation for survival. Time: Day 15, Day 29Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Proportion of participants with at least one-point improvement from baseline in clinical status Time: Baseline, Day 15, Day 29Treatment of patients with Covid-19 associated pneumonia using intravenous injection of allogenic pooled olfactory mucosa-derived mesenchymal stem cells
Description: Number of patients cured, assessed by PCR in addition to chest CT scan
Measure: Number of cured patients Time: 3 weeksDescription: MSC infusion related adverse events assessed by blood count, liver and function tests
Measure: Number of patients with treatment-related adverse events Time: 3 weeksNovel coronavirus SARS(Severe Acute Respiratory Syndrome)-CoV-2 was first identified during the outbreak in Wuhan, China in December 2019 with the now resulting pandemic. Aggressive supportive care is the mainstay of treatment currently and rescue with lung protective mechanical ventilation is essential for survival in patients with severe acute respiratory distress syndrome. Despite supportive care, mortality is significant in hospitalized patients in the U.S., especially among patients > 65 years of age. Pharmacologic treatments to decrease disease severity are urgently needed. Hydroxychloroquine is currently widely used for treatment of autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis, and it has been used to prevent and treat malaria. In vitro and in vivo antiviral activity towards SARS-CoV-2 has been reported. Since hydroxychloroquine has been used for decades its properties as a drug are well known. The investigators propose a pragmatic trial of hydroxychloroquine in moderately ill hospitalized adults with SARS-CoV-2 pneumonia with the hypothesis that hydroxychloroquine reduces severity of acute lung injury caused by SARS-CoV-2 infection.
Description: paO2
Measure: Change from Baseline Oxygenation on Day 1 to Day 5 Time: Day 1 of treatment to day 5 of treatmentDescription: FIO2
Measure: Change from Baseline Oxygenation at Day 5 Time: Day 1 of treatment to day 5 of treatmentDescription: Length in hours
Measure: Intensive Care length of stay Time: Day 0 to Day 28Description: Length in hours
Measure: Required Mechanical Ventilation Time: Day 0 to Day 28Description: Length in hours
Measure: Required Oxygen supplementation Time: Day 0 to Day 28Description: Length in hours
Measure: Hospitalization length of Stay Time: Day 0 to Day 28Description: Date of Death
Measure: Mortality Time: Day 0 to Day 28Description: Cardiologist Diagnostic Documentation
Measure: Cardiac Arrhythmia - Polymorphic Ventricular Tachycardia Time: Day 0 to Day 28Description: Cardiologist Diagnostic Documentation
Measure: Cardiac Arrhythmia - Ventricular Tachycardia Time: Day 0 to Day 28Description: Cardiologist Diagnostic Documentation
Measure: Cardiac Arrhythmia - Lengthening QTc Time: Day 0 to Day 28The study will assess the efficacy and safety of MAS825 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function
Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.
Measure: APACHE II severity of disease score on Day 15 or on day of discharge (whichever is earlier) Time: Up to 15 daysDescription: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.
Measure: Serum C-reactive protein (CRP levels) Time: Up to 15 daysDescription: Ferritin is a blood test marker for inflammation in the body. For a standard Ferritin test, a normal reading is less than 300 micrograms per liter (μg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline Ferritin as a covariate.
Measure: Ferritin levels Time: Up to 15 daysDescription: Proportion of participants without the need for invasive mechanical ventilation for survival.
Measure: Proportion of participants without the need for invasive mechanical ventilation Time: Day 15, Day 29Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Proportion of participants with at least one level improvement in clinical status Time: Day 15, Day 29Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Clinical status over time Time: Up to 15 daysA multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.
Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 30th day Time: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 7th day Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 14th day Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Hospital discharge or intrahospital death
Measure: Time until hospital discharge (days). Time: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admissionDescription: ICU discharge or ICU death
Measure: Time until discharge from ICU (days) Time: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admissionDescription: Death and time to death
Measure: Time to death Time: In a 30 days follow up periodDescription: Time until complete functional recovery (according to basal status).
Measure: Time until complete functional recovery Time: Whenever the patient returns to basal functional status until 1 month from dischargeDescription: Percentage of participants with adverse events / serious adverse events
Measure: Percentage of participants with adverse events / serious adverse events Time: In a 30 days follow up periodDescription: Percentage of patients with negative SARS-CoV-3 PCR
Measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: D Dimer plasma concentration
Measure: D Dimer plasma concentration at Day 14th Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Ferritin plasma concentration
Measure: Ferritin plasma concentration at Day 13th Time: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Plasma concentration of neutralizing antibodies
Measure: Plasma concentration of neutralizing antibodies at Day 2nd Time: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Plasma concentration of neutralizing antibodies
Measure: Plasma concentration of neutralizing antibodies at Day 7th Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Post-transfusion adverse reactions between study groups
Measure: Post-transfusion adverse reactions Time: In a 30 days follow up periodIn December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. The aim of the study is to investigate the influence of extracorporeal cytokine adsorption on interleukin-6-levels and time to successful ECMO explantation under controlled conditions in patients with particularly severe COVID-19 disease requiring extracorporeal membrane oxygenation.
Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)
Measure: IL-6 reduction by 75% or more after 72 hours as compared to the baseline measurement Time: 72 hoursDescription: time to successful ECMO-explantation within 30 days after randomization
Measure: time to successful ECMO-explantation Time: 30 daysDescription: Ventilator free days (VFD) in the first 30 days after randomization, where invasive mechanical ventilation (IMV), non-invasive ventilation (NIV) and ECMO are defined as ventilator days. VFD=0, if the patient dies in the first 30 days after randomization
Measure: Ventilator free days (VFD) Time: 30 daysDescription: Time to extubation from ventilation and explantation from ECMO. Death under ventilation and/or ECMO will be analyzed as a competing event. The time will be censored at the time of last visit for surviving patients under ventilation and/or ECMO.
Measure: Time to extubation from ventilation and explantation from ECMO Time: 30 daysDescription: Overall survival time, defined as time from randomization to death. The time will be censored at the time of last visit for surviving patients.
Measure: Overall survival time Time: 30 daysDescription: Days on intensive care unit (ICU)
Measure: Days on intensive care unit (ICU) Time: 30 daysDescription: Vasopressor dosage of adrenaline, noradrenaline, vasopressin, and dobutamine at 24, 48,72 h
Measure: Vasopressor dosage Time: 24, 48, 72 hoursDescription: Total fluid[ml] substitution and fluid balance [ml] at 24, 48, 72 h
Measure: Fluid substitution and fluid balance Time: 24, 48, 72 hoursDescription: Serum lactate at 24, 48, 72 h
Measure: Serum lactate Time: 24, 48, 72 hoursDescription: Urine output at 24, 48, 72 h
Measure: Urine output Time: 24, 48, 72 hoursDescription: Willebrand factor at 24, 48, 72 h
Measure: Willebrand factor Time: 24, 48, 72 hoursDescription: d-dimers at 24, 48, 72 h
Measure: d-dimers Time: 24, 48, 72 hoursDescription: interleukin-6 levels at 24, 48, 72 h
Measure: interleukin-6 levels Time: 24, 48, 72 hoursDescription: Sequential Organ Failure Assessment Score at 24, 48, 72 h (values from 6 to 24, where the higher values explain higher disease severity)
Measure: SOFA-Score Time: 24, 48, 72 hoursDescription: serious complications or malfunctions related to the CytoSorb device
Measure: serious adverse device effects Time: 30 daysDescription: unintended air in the ECMO system during operation of the device
Measure: adverse event of special interest: air in the ECMO system Time: 30 daysDescription: unintended blood-clotting in the ECMO system during operation of the device
Measure: adverse event of special interest: blood-clotting in the ECMO system Time: 30 daysDescription: major bleeding events
Measure: adverse event of special interest: bleeding complications Time: 30 daysNasal High Flow oxygen therapy (NHF) is commonly used as first line ventilatory support in patients with acute hypoxemic respiratory failure (AHRF). It's use has been initially limited in Covid-19 patients presenting with AHRF. The aim of the study is to describe the use of NHF in Covid-19-related AHRF and report the changes in the respiratory-oxygenation index (termed ROX index) over time in these patients.
Description: values of ROX index during ICU stay
Measure: Changes in ROX index Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: percentage of patients requiring intubation
Measure: NHF failure Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: level of flow used with NHF
Measure: NHF flow Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: level of inspired fraction in oxygen used with NHF
Measure: NHF inspired fraction in oxygen Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: level of pulse oxymetry during NHF therapy
Measure: oxygenation Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: respiratory rate during NHF therapy
Measure: respiratory status Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: defining the values of ROX index associated with intubation
Measure: prediction of intubation Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: defining the values of ROX index associated with NHF success (no intubation required)
Measure: prediction of NHF success Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsThis study seeks to assess the impact of physical and pulmonary rehabilitation on patients who have been diagnosed with COVID-19 in the short and long term in hopes of establishing a best practices protocol for treatment of future patients with this disease.
Description: Validated test demonstrating functional gait capacity and endurance; measuring change in capacity over time in 6 month increments.
Measure: Change in 6 Minute Walk Test Time: From 6 to 24 months post diagnosisDescription: Validated questionnaire assessing function and quality of life for patients with pulmonary function issues
Measure: Change in Short Form 35 (SF-36) Questionnaire Time: From 6 to 24 months post diagnosisDescription: Use of grip dynamometer and isokinematic lower extremity testing to determine muscle capacity
Measure: Change in Strength testing Time: From 6 to 24 months post diagnosisDescription: Measures lung output capacity
Measure: Change in Peak Flow Meter Test Time: From 6 to 24 months post diagnosisThis is a Phase II, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of MSTT1041A (astegolimab) or UTTR1147A in combination with standard of care (SOC) compared with matching placebo in combination with SOC in patients hospitalized with severe coronavirus disease 2019 (COVID-19) pneumonia.
Molecular testing (e.g PCR) of respiratory tract samples is the recommended method for the identification and laboratory confirmation of COVID-19 cases. Recent evidence reported that the diagnostic accuracy of many of the available RT-PCR tests for detecting SARS-CoV2 may be lower than optimal. Of course, the economical and clinical implications of diagnostic errors are of foremost significance and in case of infectious outbreaks, namely pandemics, the repercussions are amplified. False positives and false-negative results may jeopardize the health of a single patient and may affect the efficacy of containment of the outbreak and of public health policies. In particular, false-negative results contribute to the ongoing of the infection causing further spread of the virus within the community, masking also other potentially infected people.
Description: assess if inpatients who presented with pneumonia but had a negative test for Covid-19 are positive at the serology for SARS-CoV-2.
Measure: Serology Time: 3 weeksDescription: to find if the combination of CT scan and serology could help us in the identification of those patients who were initially negative at laboratory testing alone.
Measure: Efficacy of CT scan and Serology Time: 3 weeksDescription: the efficacy of different pharmaceutical treatments against Covid-19
Measure: Efficacy of different pharmaceutical treatments Time: 3 weeksCoronavirus 2 (SARS-CoV2) has been identified as the pathogen responsible for severe acute respiratory syndrome associated with severe inflammatory syndrome and pneumonia (COVID-19). Haemostasis abnormalities have been shown to be associated with a poor prognosis in these patients with this pneumonia. In a Chinese series of 183 patients, the hemostasis balance including thrombin time, fibrinogenemia, fibrin degradation products and antithrombin III were within normal limits. Only the D-Dimer assay was positive in the whole cohort with an average rate of 0.66 µg / mL (normal <50 µg / mL). These hemostasis parameters were abnormal mainly in patients who died during their management; the levels of D-dimers and fibrin degradation products were significantly higher while the antithrombin III was reduced. The findings on the particular elevation of D-dimers in deceased patients as well as the significant increase in thrombin time were also reported in another series. Higher numbers of pulmonary embolisms have been reported in patients with severe form of SARS-COV2 (data in press). This research is based on the hypothesis that the existence of deep vein thrombosis (DVT) could make it possible to screen patients at risk of pulmonary embolism and to set up a curative anticoagulation. The main objective is to describe the prevalence of deep vein thrombosis in patients hospitalized in intensive care for acute respiratory failure linked to documented SARS-COV2 pneumonia, within 24 hours of their admission.
Description: The primary outcome measure will be the percentage of patients with one or more DVTs from a lower extremity ultrasound scan.
Measure: percentage of patients with one or more DVTs. Time: 28 daysSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused mass mortality in the last 3 months that necessitates urgent development of new therapeutical agents. So far there is no effective anti-viral drug to reduce viral load that has critical importance to prevent progress into severe viral pneumonia and systemic hyper inflammation state. This project is to offer a biologic agent based on T cell derived exosomes. This is a novel approach using our proprietary protocols for drug development. This clinical trial is to test the safety and efficacy of this new agent following targeted delivery by metered dose inhaler. The project have received proper approvals from the Turkish Ministry of Health and Erciyes University, Kayseri Turkey. Turk-Patent Application Number: PCT/TR2020/050302
Description: Safety Assessment
Measure: Adverse reaction (AE) and severe AE (SAE) Time: 28 daysDescription: Time to Clinical Recovery (TTCR)
Measure: Efficacy Assessment Time: 28 daysDescription: Efficacy Assessment
Measure: The Rate of Recovery Without Mechanical Ventilator Time: 28 daysThis is a Phase 2, proof of concept, randomized, placebo-controlled, multicenter study to evaluate the ability of LB1148 to attenuate pulmonary dysfunction associated with COVID-19 pneumonia. The primary objective of this study is to determine if enteral administration of LB1148 will effect disease progression in hospitalized patients with moderate to severe COVID-19 via measurement of the proportion of subjects alive and free of respiratory failure at Day 28.
Description: The proportion of subjects alive and free of respiratory failure at Day 28.
Measure: Effect of LB1148 on disease progression via measurement of the proportion of patients who are alive and free of respiratory failure. Time: 28 DaysDescription: Number and proportion of patients with improved clinical status as assessed by a 9-point ordinal scale of disease severity at fixed timepoints (Days 3, 5, 7, 8, 10, 14, 28)
Measure: Clinical status at fixed time points Time: Measured at 3, 5, 7, 8, 10, 14 and 28 DaysDescription: Length of hospital stay (live discharge)
Measure: Duration of hospital stay Time: 28 DaysDescription: Number and proportion of patients requiring admission to the intensive care unit
Measure: Measurement of the number and proportion of patients requiring admission to the intensive care unit (ICU) during hospitalization Time: 28 DaysDescription: Length of ICU stay
Measure: Duration of ICU stay Time: 28 DaysDescription: Number and proportion of patients requiring invasive mechanical ventilation
Measure: Invasive mechanical ventilation requirements Time: 28 DaysDescription: Length of time patients require invasive mechanical ventilation
Measure: Duration of invasive mechanical ventilation Time: 28 DaysDescription: The number and proportion of patients deceased at Day 28
Measure: All-cause 28-day mortality Time: 28 DaysDescription: The incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Measure: Safety and tolerability of LB1148 Time: 28 DaysThis study aims to use the regenerative and repair abilities of stem cells to fight against the harmful effects of the novel coronavirus Covid-19 and therefore develop a treatment strategy. It is known that fatalities from this virus is largely caused by its damage to lungs and other organs. As the disease progresses, these organs fail and lead to mortality. Our hope is that the stem cell transplantation from healthy donors will repair the damage caused by the virus and result in a healthy recovery.
Description: Improvement of clinical symptoms related to Covid-19 infection (fever, pneumonia, shortness of breath)
Measure: Clinical improvement Time: 3 monthsDescription: Improvement of lungs assessed by CT Scan
Measure: Lung damage improvement Time: 3 monthsDescription: Negative, measured by RT-PCR laboratory tests for the virus
Measure: Sars-Cov-2 viral infection laboratory test Time: 3 monthsDescription: Cell types and numbers
Measure: Blood test Time: 3 monthsThere is urgent need of an effective therapy for Covid-19. To date, the best treatment of SARS-CoV-2 infection is unknown. Baricitinib has been identified as potential treatment for 2019-nCoV acute respiratory disease, because of its immunomodulating and hypothesized antiviral activity. This is a multicenter randomized clinical trial that aims to evaluate the efficacy and safety of baricitinib in patients with SARS-CoV2 pneumonia. Patients will be randomized to receive or not baricitinib as adjunctive therapy. All patients will continue to receive the ongoing standard therapy: chloroquine/idrossichloroquine and low-molecular weight heparin (LMWH) eventually associated with ritonavir/lopinavir or darunavir/ritonavir will be allowed for all included patients. The primary endpoint measure is the efficacy of baricitinib in reducing the number of patients requiring invasive ventilation after 7 and 14 days of treatment. Secondary endpoints will be mortality rates and toxicity of baricitinib.
Description: Reduction of the number of patients requiring invasive ventilation
Measure: Need of invasive mechanical ventilation Time: after 7 and 14 days of treatmentDescription: Proportion of any cause deaths
Measure: Mortality Time: 14- and 28-days from randomizationDescription: Days from randomization to invasive mechanical ventilation
Measure: Time to invasive mechanical ventilation Time: 30 daysDescription: Days from randomization to independence from non-invasive mechanical ventilation
Measure: Time to independence from non-invasive mechanical ventilation Time: 30 daysDescription: Days from randomization to independence from oxygen therapy
Measure: Time to independence from oxygen therapy Time: 30 daysDescription: Days from randomization to improvement in oxygenation for at least 48 hours
Measure: Time to improvement in oxygenation for at least 48 hours Time: 30 daysDescription: Days of hospital stay
Measure: Length of hospital stay Time: 30 daysDescription: Days of ICU stay
Measure: Length of ICU stay Time: 30 daysDescription: Changes in pulmonary echography
Measure: Instrumental response Time: 30 daysDescription: Rate of adverse events codified by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0
Measure: Proportion of adverse events Time: 30 daysIn this research study the investigators want to learn more about the potential benefit of radiation to the lung to improve the health of patients who are hospitalized with Coronavirus-19 (COVID-19) due to infection with a virus called SARS-CoV-2. This infection causes inflammation of the lung, which can make it difficult to breathe. As a result, patients may need supplemental oxygen or be placed on a ventilator. The investigators believe that low dose radiation therapy to the lung may reduce this inflammation and increase the likelihood that patients will need less oxygen support such as ventilation or supplemental oxygen, or be discharged from the hospital in fewer days, compared to without radiation therapy. The amount of radiation is much lower than what is typically used to treat other conditions such as cancer, although it is higher than the dose used for routine medical imaging.
Description: Subjects will be treated with 100 cGy irradiation to a single (right-sided) lung (dose level 1) or 100 cGy irradiation to both lungs (dose level 2) following a 3 + 3 dose escalation scheme
Measure: Phase 1: Feasibility and safety of treating hospitalized patients with SARS-CoV-2 pneumonia with single or bilateral whole lung irradiation Time: 4 days after randomizationDescription: The ordinal scale is an assessment of the clinical status on a given day. Each day, the worst (lowest) score from the previous day will be recorded as the score for that previous day. The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring low flow supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care Not hospitalized
Measure: Phase 2: Proportion with clinical improvement on a 7-point ordinal scale on day 4 after randomization Time: 4 days after randomizationThe novel coronavirus SARS-CoV2 clinically presents with pneumonia, characterised by fever, cough, dyspnea. The severity of the disease varies widely with evidence of mild disease in the majority of confirmed cases, severe pneumonia-dyspnea, hypoxia or lung involvement at imaging within 24-48 hours- and critical disease with respiratory failure, shock or multi-organ failure in particular patient cohorts. Imaging plays a key role is diagnosis and progression of this disease.
Description: Evaluate RX imaging aspects at the time of diagnosis and until discharge.
Measure: Describe qualitative and quantitative variables Time: Through study completion, an average of 5 monthsDescription: Evaluate CT imaging aspects at the time of diagnosis and until discharge.
Measure: Describe qualitative and quantitative variables Time: Through study completion, an average of 5 monthsDescription: Correlate imaging findings to OS
Measure: Ability of imaging to predict disease progression Time: Through study completion, an average of 5 monthsDescription: Correlate imaging findings over time
Measure: Ability of imaging to predict disease evolution Time: Through study completion, an average of 5 monthsDescription: Correlate imaging findings to age and sex
Measure: Imaging findings and demographic data Time: Through study completion, an average of 5 monthsDescription: Correlate imaging findings to laboratory values
Measure: Imaging findings and laboratory exams Time: Through study completion, an average of 5 monthsThe host response against the coronavirus 2 (SARS-CoV-2) appears to be mediated by a 'cytoquine storm' developing a systemic inflammatory mechanism and an acute respiratory distress syndrome (ARDS), in the form of a bilateral pneumonitis, requiring invasive mechanical ventilation (IMV) in an important group of patients. In terms of preventing progression to the critical phase with the consequent need of admission to the intensive care units (ICU), it has been recently proposed that this inflammatory cytoquine-mediated process can be safely treated by a single course of ultra-low radiotherapy (RT) dose < 1 Gy. The main purpose of the study was to analyze the efficacy of ultra low-dose pulmonary RT, as an anti-inflammatory intention in patients with SARS-Cov-2 pneumonia with a poor or no response to standard medical treatment and without IMV.
Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)
Measure: Oxygen Therapy Status at Day 2 Time: At 2 after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)
Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2 Time: At 2 days after RTDescription: Pa02 / Fi02 > 300 mmHg
Measure: Blood Gas Analysis at Day 2 Time: At 2 days after RTDescription: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)
Measure: Blood Test at Day 2 Time: At 2 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)
Measure: Oxygen Therapy Status at Day 5 Time: At 5 after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)
Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5 Time: At 5 days after RTDescription: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)
Measure: Blood Test at Day 5 Time: At 5 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)
Measure: Oxygen Therapy Status at Day 7 Time: At 7 after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)
Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7 Time: At 7 days after RTDescription: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)
Measure: Blood Test at Day 7 Time: At 7 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)
Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7 Time: At 7 days after RTDescription: Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death)
Measure: Recovery time Time: From RT administration until hospital discharge or deathDescription: COVID-19 negativization test
Measure: COVID-19 status Time: At 7 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)
Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1 Time: At 1 month after RTDescription: Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales.
Measure: Acute Toxicity Time: 1-3 months after RTA randomized placebo controlled trial to assess the clinical outcome in COVID-19 Pneumonia following administration of Silymarin owing to its role as a p38 MAPK pathway inhibitor and its antiviral, anti-inflammatory and anti-oxidant effects
Description: Defined as the time from randomization to an improvement of two points (from the status of randomization) on seven category ordinal scale or live discharge from the hospital, whichever comes first.
Measure: Time to clinical improvement Time: 7-28 daysDescription: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14
Measure: Clinical outcome Time: 7-14 daysDescription: Time in days patient was intubated
Measure: Duration of Mechanical Ventilation Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 daysDescription: Total days of hospitalization
Measure: Hospitalization Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 daysDescription: number of days patient remained with positive RT-PCR SARS-CoV-2 swab
Measure: Virologic Response Time: Randomization till discharge, up to 28 daysDescription: Any adverse events whether related to medication or not
Measure: Adverse events Time: Randomization till hospital discharge, up to 28 daysSerious pneumonia is a serious inflammation of the lungs caused by various pathogens, resulting in severe bacteraemia or toxemia, which in turn causes blood pressure drop, shock, blurred consciousness, restlessness, delirium and coma, etc., and requires intensive care and treatment in intensive care unit (ICU) because of its seriousness. There is an upward trend in the number of clinically immunosuppressed host patients, including long-term use of glucocorticoids for rheumatoid immune diseases and kidney diseases, tumor chemotherapy, organ transplantation, etc. A huge risk for these patients is the diagnosis and treatment of infections, especially lung infections. We have previously observed a significant increase in mortality from severe pneumonia in immunosuppressed patients, and our recent analysis of 204 patients with novel coronavirus pneumonia found that low lymphatic counts, immunosuppression, etc. were independent risk factors for death in patients. Early diagnosis and timely treatment are the main means to reduce the mortality rate of severe pneumonia. CD55 is an important complement regulatory protein that inhibits C3 and C5 activation by blocking the formation and accelerating the decay of new C3 and C5 convertases, both of which mediate the downstream action of all three complement activation pathways, and CD55 protects host cells from complement attack. Our previous study found that CD55 was significantly elevated in patients with severe pneumonia. Therefore, this project proposes "Early diagnosis of severe pneumonia based on combination of biomarkers with new generation pathogenesis and early clinical manifestations". It is proposed to validate the predictive effects of recently discovered markers such as CD55, HBP and CD64 on severe pneumonia through prospective single-center clinical studies, explore the establishment of new predictive models for early diagnosis of severe pneumonia, and optimize the diagnosis and treatment strategy of severe pneumonia, and provide new ideas for accurate treatment of severe pneumonia.
This is a Phase I open-label interventional study which will test the efficacy of ResCure™ in the treatment of patients with COVID-19 infection.
Description: Number of days from COVID-19 diagnosis to recovery via RT-PCR
Measure: The rate of recovery of mild or moderate COVID-19 in patients using ResCure™ Time: 12 WeeksDescription: Reduction and/or progression of symptomatic days, reduction of symptom severity
Measure: Reduction or progression of symptomatic days Time: 12 WeeksDescription: Pulse from baseline to 12 weeks
Measure: Assess the safety of ResCure™ via pulse Time: 12 WeeksDescription: Oxygen saturation from baseline to 12 weeks
Measure: Assess the safety of ResCure™ via oxygen saturation Time: 12 WeeksDescription: EKG from baseline to 12 weeks
Measure: Assess the safety of ResCure™ via EKG Time: 12 WeeksDescription: Assess Adverse Events and Serious Adverse Events due to ResCure™
Measure: Assess Tolerability of ResCure™ Time: 12 WeeksThe COVID-19 pandemic, commonly referred to as "coronavirus", first began in the city of Wuhan, China in December 2019. This virus has since spread globally, with infections reported in nearly every country. COVID-19 targets the body's respiratory system, where infections can be found in the nose, throat and lungs. The effect of COVID-19 infection is very variable, where many people might not know that they have been infected and have recovered from COVID-19. However, COVID-19 infection can cause people to have difficulty breathing. This can be severe enough to require hospitalisation and potentially intensive care treatment. While they are being treated in hospital, COVID-19 infected patients can be found to have inflamed tissue in their lungs (referred to medically as "pneumonitis"). This inflammation is thought to be caused by their body's immune systems overacting to the infection rather than the COVID-19 virus itself. By potentially dampening down this overreaction of their immune system, it is hoped that COVID-19 patients with inflamed lungs have better and quicker chance to survive. Mesenchymal stromal cells (MSCs) have been shown to have anti-inflammatory and healing properties on injured tissue. MSCs have been trialled in various diseases but have not yet been tested on patients with COVID-19. In this study, the investigators will obtain bone marrow from healthy volunteers to develop a cell-based treatment for COVID-19-related pneumonitis. The investigators will also determine whether it is feasible to recruit bone marrow donors in a clinically useful timeframe to treat COVID-19 patients. A future trial, COMET20, will use the bone marrow-derived MSCs (BM-MSCs) manufactured in COMET20d to treat COVID-19 patients suffering with pneumonitis, to determine whether the BMMSCs can reduce the likelihood for mechanical ventilation and reduce hospitalisation.
Description: Successful identification of healthy volunteers in acceptable timeframe (i.e. within days) to donate bone marrow.
Measure: Determine feasibility of recruiting healthy volunteers in a clinically useful timeframe. Time: 3 or more participants recruited in 1 monthDescription: Successful manufacture of bone marrow-mesenchymal stromal cells suitable for clinical use
Measure: Manufacture a cell-based product suitable for clinical use Time: Successfully opening the next phase of the trial in approx. 2 monthsDescription: Ability to prepare a dossier acceptable to the MHRA. Success will achieved if the dossier is deemed acceptable.
Measure: Establishment of a robust process of production Time: Successfully opening the next phase of the trial in approx. 2 monthsDescription: Successful manufacturing of products will be defined initially as the award of a Manufacturers Specials Licence to the CCTL to allow the manufacture of Bone Marrow-Mesenchymal Stromal Cells for compassionate use.
Measure: Production of stability data to be used in the MHRA dossier for the COMET clinical trial. Time: Successfully opening the next phase of the trial in approx. 2 monthsDescription: Successful manufacturing of products will be subsequently defined by production under MA(IMP) licence, allowing for future production under CTIMP and CTA.
Measure: Production of cell-based products to be administered to COVID-19 patients with severe pneumonitis. Time: Successfully opening the next phase of the trial in approx. 2 monthsDescription: Successful manufacturing of products, under MA(IMP) licence will be defined as the availability of Bone Marrow-Mesenchymal Stromal Cells to be used in the context of the COMET20 clinical trial.
Measure: Analysis of cells for understanding production, manufacture and related research. Time: Successfully opening the next phase of the trial in approx. 2 monthsThis study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.
Description: Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm
Measure: Reduction in the dependency on oxygen supplementation Time: within day 14 of treatmentDescription: Response is defined as a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Proportion of responders (using the WHO 7-point ordinal scale) Time: Day 7, 14, and 28Description: Time from date of randomization to the date with a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Time to response (using the WHO 7-point ordinal scale) Time: Within day 28 of interventionDescription: Proportion of patients with at least two-point improvement in clinical status
Measure: Proportion of improving patients (using the WHO 7-point ordinal scale) Time: At day 7, 14, and 28Description: Time to resolution of fever (for at least 48 hours) in absence of antipyretics, or discharge, whichever is sooner
Measure: Time to resolution of fever Time: Within day 28 of interventionDescription: COVID-19-related death
Measure: Reduction in case fatality Time: Within day 28 of interventionDescription: Proportion of hospitalized patients who died or required mechanical ventilation (WHO Categories 6 or 7)
Measure: Proportion of patient requiring mechanical ventilation/deaths Time: Within day 14 of interventionDescription: Change of the following serological markers over follow-up (C-reactive protein; Ferritin; D-Dimer)
Measure: Change in biochemical markers Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Median changes of NEWS2 score from baseline
Measure: Median changes in the National Early Warning Score 2 (NEWS2) Time: At day 7, 14, and 28Description: Time to clinical improvement (as defined as a NEWS2 score of 2 or less maintained for at least 24 hours or discharge, whichever comes first)
Measure: Time to clinical improvement as evaluated with the National Early Warning Score 2 (NEWS2) Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Variations from baseline to subsequent timepoints (when available) in terms of percentage of lung involvement, modifications in the normal parenchyma, ground glass opacities (GGO), crazy paving pattern,parenchymal consolidations, and evolution towards fibrosis.
Measure: Variations in radiological findings Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Number of patients with treatment- related side effects (as assessed by Common Terminology Criteria for Adverse Event (CTCAE) v.5.0), serious adverse events, adverse events of special interest, clinically significant changes in laboratory measurements and vital signs
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: By day 84Description: To evaluate the primary and secondary endpoints in different subgroups of patients: mild respiratory failure: PaO2/FiO2 ≤ 300 and > 200 mmHg; moderate respiratory failure: PaO2/FiO2 ≤ 200 and > 100 mmHg
Measure: Clinical efficacy of mavrilimumab compared to the control arm by clinical severity Time: Within day 28 of interventionDescription: Median changes in serum IL-6
Measure: Changes in serum IL-6 (exploratory biomarker) Time: By day 84Description: Median changes in serum IL-1 receptor antagonist
Measure: Changes in serum IL-1RA (exploratory biomarker) Time: By day 84Description: Median changes in serum TNF-alpha
Measure: Changes in serum TNF-alpha (exploratory biomarker) Time: By day 84Description: Median variations in haemoglobin and leucocyte counts
Measure: Changes in CBC + differential (exploratory biomarker) Time: By day 84Description: Median titres od anti-SARS-CoV2 antibodies
Measure: Level of anti-SARS-CoV2 antibodies (exploratory biomarker) Time: By day 84Description: Proportion of patients with a positive swab for SARS-CoV2 by PCR
Measure: Virus eradication (exploratory biomarker) Time: By day 84Description: Proportion of patients who developed anti-drug antibodies
Measure: Anti-drug antibodies (exploratory biomarker) Time: By day 84The purpose of this open label, randomized, study is to obtain information on the safety and efficacy of 80 ppm Nitric Oxide given in addition to the standard of care of patients with COVID-19 caused by SARS-CoV-2.
Description: Time to deterioration measured by need for NIV, HFNC or intubation
Measure: Time to deterioration Time: 14 DaysDescription: Time to non-invasive ventilation
Measure: Time to NIV Time: 14 DaysDescription: Time to high flow nasal cannula
Measure: Time to HFNC Time: 14 DaysDescription: Time to intubation
Measure: Time to intubation Time: 14 daysDescription: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93%
Measure: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93% Time: 14 daysDescription: Need for supplemental oxygen
Measure: Need for supplemental oxygen Time: 14 daysDescription: Change in viral load
Measure: Change in viral load Time: 30 daysDescription: Duration of the Hospital Length of Stay (LOS)
Measure: Duration of the Hospital Length of Stay (LOS) Time: 14 daysDescription: Mortality rate at Day 30
Measure: Mortality rate at Day 30 Time: 30 daysThe purpose of this study is to see if this plasma can be safely used in humans with COVID-19 and to see if it improves patients' health as compared to not using it in patients with pneumonia caused by SARS-CoV-2.
Description: Cumulative incidence of serious adverse events (SAEs) at Study Day 29.
Measure: Participants with serious adverse events. Time: Up to 29 days from treatmentDescription: Severity is measured by the 8-point ordinal clinical severity scale at D29 where 1 is the best state to be in and 8 is the worst (equals death). The severity score is based on a procedure by Shaw and Fay 2016, which ranks participants based on their Day 29 ordinal severity. [Shaw PA, Fay MP. A rank test for bivariate time‐to‐event outcomes when one event is a surrogate. Statistics in medicine. 2016 Aug 30;35(19):3413-23]
Measure: Comparison of clinical severity score between patients on the experimental versus control arms; Time: Up to 29 days from treatmentDescription: Time to recovery, defined by time to levels 1-3 on the ordinal scale
Measure: Clinical status assessment, using 8-point ordinal scale, of convalescent plasma administration by comparing treatment vs control arms Time: Up to 29 days from treatmentDescription: Time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first.
Measure: Clinical status assessment using the National Early Warning Score (NEWS) of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment, daily while hospitalized until discharge or death and on Days 15 and 29.Description: Oxygen-free days to Day 29.
Measure: Oxygen-free days of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment to Day 29Description: Incidence of new oxygenation use up to Day 29.
Measure: Incidence of new oxygenation use up to Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment to Day 29.Description: Days of new oxygen use up to Day 29.
Measure: Duration of new oxygen use up to Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment to Day 29.Description: Days of non-invasive ventilation/high flow oxygen up to Day 29
Measure: Non-invasive ventilation/high flow oxygen days up to Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment to Day 29.Description: Incidence of non-invasive ventilation up to Day 29.
Measure: Incidence of non-invasive ventilation/high flow oxygen up to Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment to Day 29.Description: Days of non-invasive ventilation/high flow oxygen up to Day 29
Measure: Duration of non-invasive ventilation/high flow oxygen up to Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment to Day 29.Description: Ventilation/ECMO free days up to Day 29. mechanical ventilation or ECMO use during the study.
Measure: Ventilator/ECMO free days to Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment to Day 29.Description: Incidence of new mechanical ventilation or ECMO use up to Day 29.
Measure: Incidence of new mechanical ventilation or ECMO use of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment to Day 29.Description: Days of new mechanical ventilation or ECMO use up to Day 29.
Measure: Duration of new mechanical ventilation or ECMO use of convalescent plasma administration by comparing treatment vs control arms Time: From enrollment to Day 29.Description: Duration of hospitalization.
Measure: Duration of hospitalization of convalescent plasma administration by comparing treatment vs control arms Time: To Day 29Description: D14 and D28 mortality.
Measure: Mortality of convalescent plasma administration by comparing treatment vs control arms Time: To Day 28Description: Cumulative incidence of SAEs through Day 29.
Measure: Cumulative incidence of SAEs through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29Description: Cumulative incidence of Grade 3 and Grade 4 clinical and/or laboratory adverse events through Day 29.
Measure: Cumulative incidence of Grade 3 and Grade 4 clinical and/or laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29Description: Changes in WBC with differential on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).
Measure: Changes in WBC with differential through day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29Description: Changes in hemoglobin measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).
Measure: Changes in hemoglobin measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29Description: Changes in platelets measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).
Measure: Changes in platelets measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29.Description: Changes in creatinine measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).
Measure: Changes in creatinine measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29.Description: Changes in glucose measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).
Measure: Changes in glucose measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29.Description: Changes in bilirubin measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).
Measure: Changes in bilirubin measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29Description: Changes in ALT measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).
Measure: Changes in ALT measurement laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29Description: Changes in AST measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).
Measure: Changes in AST measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29.Description: Changes in PT measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).
Measure: Changes in PT measurement laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms Time: Through Day 29.Novel Coronavirus 2019 Disease (COVID-19) mortality is highly associated with viral pneumonia and its complications. Accurate and prompt diagnosis shown to be effective to improve outcome by providing early treatment strategies. While chest X-ray (CXR) and computerized tomography (CT) are defined as gold standard, given the advantage of being an ionized radiation free, practical technique point of care ultrasound (POCUS) is also reported as a diagnostic tool for COVID-19. There are limited studies regarding the importance of POCUS in diagnosis and review of COVID-19. Therefore the aim of this study is to evaluate the utility of bedside lung ultrasound on diagnosis of COVID-19 for patients admitted to emergency department .
Description: Efficacy of POCUS on diagnosis of viral pneumonia caused by COVID 19
Measure: Presence of viral pneumonia caused by COVID 19 Time: 3 monthsThe objective of the study is to assess the efficacy and safety of Baricitinib in the treatment of patients with COVID-19 pneumonia. This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof of concept phase will lead to favourable results, an open-label, Phase II, randomized controlled trial will be then designed and performed to confirm the results obtained in the proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on a limited number of patients in the use of a drug new to the current condition being treated.
Description: A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)
Measure: Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria) Time: 8 daysDescription: Absence of death within 8 days from enrollment
Measure: Response to treatment: survival Time: 8 daysDescription: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days Time: 8 daysDescription: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days Time: 15 daysDescription: To quantify mortality within 8 and 15 days
Measure: Mortality Time: 8 days and 15 daysDescription: SpO2 will be assessed with the median and 25th-75th percentiles
Measure: Peripheral capillary oxygen saturation (SpO2) Time: 8 days; 15 daysDescription: PaO2/FiO2 will be assessed with the median and 25th-75th percentiles
Measure: Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2) Time: 8 days; 15 daysDescription: Number of patients over the number of patients enrolled
Measure: To assess the rate of patients admitted to the intensive care unit Time: 8 days; 15 daysDescription: Median number of days and 25th-75th percentiles
Measure: To measure the length of hospital stay Time: 8 days; 15 daysDescription: To quantify 28-day mortality
Measure: 28-day mortality Time: 28 daysDescription: Number of patients readmitted over the number patients enrolled
Measure: To quantify the rate of re-admission within 28 days Time: 28 daysDescription: Number, type, and severity of adverse events
Measure: To quantify the cumulative incidence and severity of adverse events Time: 28 daysDescription: Serial serum assessments from baseline up to 15 days
Measure: Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels; Time: 15 daysDescription: Serial serum assessments from baseline up to 15 days
Measure: TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels Time: 15 daysDescription: Serial assessments from baseline up to 15 days for viral load persistence
Measure: Viral load analyses Time: 15 daysThe purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
Description: Number of subjects alive and off of oxygen
Measure: Proportion of subjects alive and off of oxygen at day 14 Time: Day 14Description: Number of subjects alive and without respiratory failure
Measure: Proportion of subjects alive and without respiratory failure at 28 days Time: Day 28