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Hepatitis (1) Hepatitis A (1) Hepatitis C (1) Hepatitis, Alcoholic (1) Hereditary Autoinflammatory Diseases (1) Herpes Labialis (1) Herpes Zoster (1) Hodgkin Disease (1) Hyaline Membrane Disease (1) Hyperaldosteronism (1) Hypercapnia (1) Hyperphosphatemia (1) Hyperplasia (1) Hypersensitivity, Immediate (1) Hypertension, Pregnancy-Induced (1) Hypokalemia (1) Hyponatremia (1) Hypoparathyroidism (1) Hypotension (1) Iatrogenic Disease (1) Infant, Newborn, Diseases (1) Infec (1) Infecti (1) Infertility, Female (1) Infertility, Male (1) Intellectual Disability (1) Intestinal Atresia (1) Intracranial Hypertension (1) Intracranial Thrombosis (1) Jaundice, Obstructive (1) Joint Diseases (1) Keratoconjunctivitis (1) Keratosis (1) Keratosis, Actinic (1) Leishmaniasis (1) Leukemia, Lymphocytic, Chronic, B-Cell (1) Leukemia, Myeloid (1) Leukemia, Myelomonocytic, Acute (1) Leukemia, Myelomonocytic, Chronic (1) Liver Cirrhosis, Biliary (1) Liver Failure (1) Low Back Pain (1) Lung (1) Lyme Disease (1) 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D013577: Syndrome

Developed by Shray Alag, The Harker School
Sections: Correlations, Clinical Trials, and HPO

Correlations computed by analyzing all clinical trials.

Navigate: Clinical Trials and HPO


Correlated Drug Terms (281)


Name (Synonyms) Correlation
drug2858 Remestemcel-L Wiki 0.17
drug176 Ad26.COV2.S Wiki 0.15
drug753 ChAdOx1 MERS Wiki 0.14
Name (Synonyms) Correlation
drug2039 Methylprednisolone Sodium Succinate Wiki 0.14
drug2933 Ruxolitinib Oral Tablet Wiki 0.14
drug2505 Placebo Wiki 0.12
drug2202 Nitric Oxide Gas Wiki 0.11
drug2371 PARTNER-MH Wiki 0.10
drug177 Ad26.ZEBOV Wiki 0.10
drug3821 canakinumab Wiki 0.10
drug3426 Testing for SARS-CoV-2 Wiki 0.10
drug358 Awake prone positioning Wiki 0.10
drug144 AZD9833 film-coated tablet A Dose 2 Wiki 0.10
drug2566 Placebo- 1.00 mg/kg Wiki 0.10
drug431 BVRS-GamVac-Combi Wiki 0.10
drug3734 XCEL-UMC-BETA Wiki 0.10
drug1567 Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy) Wiki 0.10
drug3633 Vehicle + Heparin along with best supportive care Wiki 0.10
drug2666 Prone decubitus Wiki 0.10
drug3488 Tocilizumab 180 MG/ML Wiki 0.10
drug107 ARGX-117 Wiki 0.10
drug1743 Itolizumab IV infusion Wiki 0.10
drug894 Convalescent Immune Plasma Wiki 0.10
drug2511 Placebo (Plasma-Lyte 148) Wiki 0.10
drug2496 Physiology Wiki 0.10
drug2560 Placebo solution Wiki 0.10
drug2728 Qualitative interviews (in 40 patients : 20 with COVID-19 and 20 without COVID-19) Wiki 0.10
drug2372 PB1046 Wiki 0.10
drug1696 Interleukin-1 receptor antagonist Wiki 0.10
drug3169 Sofosbuvir/daclatasvir Wiki 0.10
drug2716 Pyronaridine-artesunate Wiki 0.10
drug2339 Opt-in Recruitment Email Wiki 0.10
drug322 Association of diltiazem and niclosamide Wiki 0.10
drug3640 Veru-111 Wiki 0.10
drug1442 HLCM051 Wiki 0.10
drug471 Best supportive care" which includes antivirals /antibiotics/ hydroxychloroquine; oxygen therapy Wiki 0.10
drug1947 MVA-BN-Filo Wiki 0.10
drug1649 IncobotulinumtoxinA 100 UNT Injection [Xeomin] Wiki 0.10
drug3857 dapansutrile capsules Wiki 0.10
drug4159 urinary NGAL, TIMP-2, IGFBP7, IL-6, viral load and metabolomic Wiki 0.10
drug4041 placebo+rHuPH20 Wiki 0.10
drug92 APL-9 Wiki 0.10
drug89 ALX148 Wiki 0.10
drug215 Alteplase 100 MG [Activase] Wiki 0.10
drug1103 Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) Wiki 0.10
drug1727 Intravenous sedation Wiki 0.10
drug112 ASP2390 Wiki 0.10
drug180 Adalimumab Wiki 0.10
drug2564 Placebo- 0.10 mg/kg Wiki 0.10
drug1792 LEAF-4L6715 Wiki 0.10
drug3386 Tele-medicine platform Wiki 0.10
drug268 Antibody test (SARS-CoV2) Wiki 0.10
drug377 BAT + Calcifediol Wiki 0.10
drug105 ARDSNet Wiki 0.10
drug60 A short video intervention Wiki 0.10
drug312 Assessing impact of COVID19 Wiki 0.10
drug695 CUROSURF® (poractant alfa) Wiki 0.10
drug1097 Drug: GS-5734 - 2.00 mg/kg Wiki 0.10
drug923 Coronary artery calcium score and cardiac computed tomographic angiography Wiki 0.10
drug1878 Low Dose (10 mg) Control Wiki 0.10
drug1266 Extracorporeal membrane oxygenation Wiki 0.10
drug2826 Recombinant S protein SARS vaccine Wiki 0.10
drug1855 Lopinavir / Ritonavir plus Ribavirin Wiki 0.10
drug1619 IgG antibodies immunoassay Wiki 0.10
drug140 AZD8154 nebuliser Wiki 0.10
drug777 Chloroquine Diphosphate Wiki 0.10
drug4163 vadadustat Wiki 0.10
drug1513 Human umbilical cord derived CD362 enriched MSCs Wiki 0.10
drug2340 Opt-out Recruitment Email Wiki 0.10
drug297 Arm exercise electrocardiographic stress test Wiki 0.10
drug239 Analogs, Prostaglandin E1 Wiki 0.10
drug3527 Treadmill electrocardiographic stress test Wiki 0.10
drug3025 Saline Placebo Wiki 0.10
drug1038 Diabetes type 2 Wiki 0.10
drug227 Ampion Wiki 0.10
drug1860 Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki 0.10
drug2141 NP-120 (Ifenprodil) Wiki 0.10
drug142 AZD9833 Oral Solution Wiki 0.10
drug3438 The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care: Wiki 0.10
drug1625 Imaging by thoracic scanner Wiki 0.10
drug3269 Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki 0.10
drug2552 Placebo of excipient(s) will be administered Wiki 0.10
drug275 Antihypertensive Agents Wiki 0.10
drug1657 Inflammatory cytokines and chemokines profiles of patients with dexmedetomidine administration Wiki 0.10
drug91 AMY-101 Wiki 0.10
drug3176 Spartan COVID-19 System Wiki 0.10
drug1032 Dexamethasone and Hydroxychloroquine Wiki 0.10
drug2148 Naltrexone Wiki 0.10
drug1100 Drug: NA-831 - 0.10 mg/kg Wiki 0.10
drug174 Activity Wiki 0.10
drug298 Artemesia annua Wiki 0.10
drug3044 Sampling salivary Wiki 0.10
drug3396 Telemedicine FU Wiki 0.10
drug276 Antioxidation Therapy Wiki 0.10
drug161 Accuchek Inform II platform Wiki 0.10
drug362 Azacitidine Wiki 0.10
drug1779 Ketamine Wiki 0.10
drug143 AZD9833 film-coated tablet A Dose 1 Wiki 0.10
drug1847 Liver function tests ,serum ferritin and PCR for COVID-19 . Wiki 0.10
drug1811 Lactoferrin (Apolactoferrin) Wiki 0.10
drug1514 Human umbilical cord mesenchymal stem cells + best supportive care Wiki 0.10
drug2806 Rapamycin Wiki 0.10
drug260 Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS) Wiki 0.10
drug1109 During COVID-19 Pandemic Wiki 0.10
drug2283 Obesity Wiki 0.10
drug962 D-dimer,CBC.ESR,CRP, Wiki 0.10
drug3691 WFI 5% glucose Wiki 0.10
drug191 Aerosolized All trans retinoic acid Wiki 0.10
drug1951 MW33 injection Wiki 0.10
drug3246 Standard therapeutic protocol Wiki 0.10
drug118 AT-527 Wiki 0.10
drug2567 Placebo- 2.00 mg/kg Wiki 0.10
drug3718 Wharton's jelly derived Mesenchymal stem cells. Wiki 0.10
drug3628 Valsartan (Diovan) Wiki 0.10
drug1096 Drug: GS-5734 - 1.00 mg/kg Wiki 0.10
drug1579 Hypertension Wiki 0.10
drug220 Aluminum hydroxide adjuvant (Alhydrogel®) Wiki 0.10
drug4020 oral polio vaccine + information Wiki 0.10
drug2379 PEEP trial Wiki 0.10
drug1859 Lopinavir 200Mg/Ritonavir 50Mg FT Test Wiki 0.10
drug550 Brexanolone Wiki 0.10
drug2019 Mesenchymal Stem Cell Wiki 0.10
drug292 Aprepitant injectable emulsion Wiki 0.10
drug3237 Standard of care therapies Wiki 0.10
drug584 CAStem Wiki 0.10
drug1101 Drug: NA-831 - 0.20 mg/kg Wiki 0.10
drug1509 Human Cord Tissue Mesenchymal Stromal Cells (hCT-MSCs) Wiki 0.10
drug2841 Regadenoson myocardial perfusion imaging stress test Wiki 0.10
drug3638 Verapamil Wiki 0.10
drug2399 PLN-74809 Wiki 0.10
drug345 Auricular percutaneous neurostimulation Wiki 0.10
drug726 Cannabis, Medical Wiki 0.10
drug311 Assessing antibody responses, neutralizing capacity and memory B-cell function Wiki 0.10
drug1659 Information Wiki 0.10
drug2900 Ringer solution Wiki 0.10
drug195 After COVID-19 Pandemic Wiki 0.10
drug3895 gammaCore® Sapphire (non-invasive vagus nerve stimulator) Wiki 0.10
drug30 2019-nCoV IgG/IgM Rapid Test Cassette Wiki 0.10
drug2321 OnabotulinumtoxinA 100 UNT [Botox] Wiki 0.10
drug186 Aerobic Exercise Training Wiki 0.10
drug2435 Patient Education Wiki 0.10
drug346 Auto-questionnaires (patients co infected HIV Sras-CoV-2) Wiki 0.10
drug1799 LSALT peptide Wiki 0.10
drug2718 Q16 testing Wiki 0.10
drug108 ARGX-117 + rHuPH20 Wiki 0.10
drug1656 Infectious Disease and Cardiology Clinical Consultations Wiki 0.10
drug2144 NaCl 0.9% Wiki 0.10
drug1351 Freestyle Libre 14 day CGM system Wiki 0.10
drug3616 VIB4920 Wiki 0.10
drug3311 Survey Group Wiki 0.10
drug1834 LifeSignals Biosensor 1AX* Wiki 0.10
drug356 Awake Prone Positioning Wiki 0.10
drug516 Blood group determination Wiki 0.10
drug376 BAT Wiki 0.10
drug288 Apple Watch Series 5 Wiki 0.10
drug223 Amiodarone Wiki 0.10
drug3277 Streptokinase Wiki 0.10
drug781 Chloroquine diphosphate Wiki 0.10
drug479 Biological collection (patients co infected HIV Sras-CoV-2) Wiki 0.10
drug160 Access to training facility Wiki 0.10
drug231 Anakinra 100Mg/0.67Ml Inj Syringe Wiki 0.10
drug3664 Virtual Reality Wiki 0.10
drug880 Continuous renal replacement therapy Wiki 0.10
drug17 14C-lazertinib Wiki 0.10
drug2401 PP-MI Intervention Wiki 0.10
drug1711 Intervention program Wiki 0.10
drug3481 Tissue plasminogen activator Wiki 0.10
drug1746 Ivermectin (IVM) Wiki 0.10
drug2565 Placebo- 0.20 mg/kg Wiki 0.10
drug1104 Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg) Wiki 0.10
drug1306 Favipiravir plus Nitazoxanide Wiki 0.10
drug1952 MW33 injection placebo Wiki 0.10
drug3870 eculizumab Wiki 0.10
drug3578 Umbilical cord Wharton's jelly-derived human Wiki 0.10
drug2515 Placebo 0.10 mg + 1.00 mg/kg Wiki 0.10
drug1637 Immunological profiling Wiki 0.10
drug1014 Defibrotide Wiki 0.10
drug4036 placebo capsules Wiki 0.10
drug3577 Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care. Wiki 0.10
drug1772 Janus Kinase Inhibitor (ruxolitinib) Wiki 0.10
drug1992 Medical Record Review - Inpatient Treatment Wiki 0.10
drug3241 Standard oxygen therapy Wiki 0.10
drug1693 Interleukin 6 (IL6) Antagonist Wiki 0.10
drug2303 Office FU Wiki 0.10
drug1127 EIT-Group Wiki 0.10
drug4120 standard procedure Wiki 0.10
drug270 Antibody titration Wiki 0.10
drug138 AZD8154 Monodose DPI presented in capsules Wiki 0.10
drug190 Aerosolized 13 cis retinoic acid Wiki 0.10
drug2516 Placebo 0.20 mg + 2.00 mg/kg Wiki 0.10
drug2486 Phosphate buffered saline Placebo Wiki 0.10
drug3913 hyperimmune plasma Wiki 0.10
drug216 Alteplase 50 MG [Activase] Wiki 0.10
drug3232 Standard of care (Paracetamol) Wiki 0.10
drug221 Alvelestat Wiki 0.10
drug1858 Lopinavir 200Mg/Ritonavir 50Mg FT Reference Wiki 0.10
drug1675 Inhaled sedation Wiki 0.10
drug2326 Online Questionnaires Wiki 0.10
drug1023 Descartes 30 Wiki 0.10
drug3763 [14C]AZD9833 Solution for Infusion, (NMT 22.8 kBq/5mL) Wiki 0.10
drug1035 Dexmedetomidine Injectable Product Wiki 0.10
drug1499 Home-use Test and Follow-up Questionnaire Wiki 0.10
drug1606 IVERMECTIN (IVER P®) arm will receive IVM 600 µg / kg once daily plus standard care. CONTROL arm will receive standard care. Wiki 0.10
drug3267 Statins (Cardiovascular Agents) Wiki 0.10
drug139 AZD8154 Placebo Monodose DPI presented in capsules Wiki 0.10
drug374 Açaí palm berry extract - natural product Wiki 0.10
drug430 BVRS-GamVac Wiki 0.10
drug2162 Nasopharyngeal swab and main laboratory Wiki 0.10
drug1614 Icosapent ethyl (IPE) Wiki 0.10
drug117 AT-001 Wiki 0.10
drug2024 Mesenchymal cells Wiki 0.10
drug2875 Respiratory Exercise Training Wiki 0.10
drug145 AZD9833 film-coated tablet B Dose 1 Wiki 0.10
drug61 A vignette intervention Wiki 0.10
drug1694 Interleukin 6 (IL6) Antagonist and corticosteroids Wiki 0.10
drug1066 Diphenhydramine Wiki 0.10
drug2665 Prone Positioning (PP) Wiki 0.10
drug361 Ayurvedic Kadha Wiki 0.10
drug303 Artesunate-amodiaquine Wiki 0.10
drug278 Antroquinonol Wiki 0.10
drug3454 Therapeutic plasma exchange (TPE) Wiki 0.10
drug146 AZD9833 film-coated tablet B Dose 2 Wiki 0.10
drug3634 Vehicle Control Wiki 0.10
drug204 Alexa Amazon Wiki 0.10
drug1793 LEAF-4L7520 Wiki 0.10
drug364 Azithromycin Wiki 0.10
drug3231 Standard of care Wiki 0.08
drug4034 placebo Wiki 0.08
drug3268 Stellate Ganglion Block Wiki 0.07
drug2029 Mesenchymal stromal cells Wiki 0.07
drug120 ATI-450 Wiki 0.07
drug3233 Standard of care (SOC) Wiki 0.07
drug3450 Therapeutic Plasma Exchange Wiki 0.07
drug246 Angiotensin II Wiki 0.07
drug2812 Ravulizumab Wiki 0.07
drug147 Abatacept Wiki 0.07
drug719 Canakinumab Wiki 0.07
drug3583 Unfractionated heparin Wiki 0.07
drug1552 Hydroxychloroquine and Azithromycin Wiki 0.07
drug1087 Dornase Alfa Inhalation Solution [Pulmozyme] Wiki 0.07
drug1511 Human immunoglobulin Wiki 0.07
drug422 BNT162b2 Wiki 0.07
drug15 100 mg/mL Virazole Wiki 0.07
drug52 50 mg/mL Virazole Wiki 0.07
drug3125 Siltuximab Wiki 0.07
drug1754 Ivermectin Oral Product Wiki 0.07
drug2621 Practice details Wiki 0.07
drug1520 Hydroxychloroquine Wiki 0.07
drug1745 Ivermectin Wiki 0.06
drug467 Best Supportive Care Wiki 0.06
drug2021 Mesenchymal Stromal Cells Wiki 0.06
drug2650 Probiotic Wiki 0.06
drug2290 Observational Wiki 0.06
drug46 3D Telemedicine Wiki 0.06
drug261 Anti-SARS-CoV2 Serology Wiki 0.06
drug421 BNT162b1 Wiki 0.06
drug2669 Prone positioning Wiki 0.06
drug207 Alirocumab Wiki 0.05
drug1228 Evolocumab Wiki 0.05
drug154 Acalabrutinib Wiki 0.05
drug790 Cholecalciferol Wiki 0.05
drug1517 Hydrocortisone Wiki 0.05
drug4113 standard care Wiki 0.05
drug304 Ascorbic Acid Wiki 0.05
drug3221 Standard of Care Wiki 0.05
drug464 Best Practice Wiki 0.04
drug3046 Sarilumab Wiki 0.04
drug3815 blood sampling Wiki 0.04
drug717 Camostat Mesilate Wiki 0.04
drug2752 Questionnaires Wiki 0.04
drug2557 Placebo oral tablet Wiki 0.03
drug229 Anakinra Wiki 0.03
drug3212 Standard care Wiki 0.03
drug3485 Tocilizumab Wiki 0.03
drug2931 Ruxolitinib Wiki 0.03
drug3603 Usual Care Wiki 0.03
drug1538 Hydroxychloroquine Sulfate Wiki 0.03
drug2037 Methylprednisolone Wiki 0.03
drug3309 Survey Wiki 0.03
drug908 Convalescent plasma Wiki 0.02
drug2741 Questionnaire Wiki 0.02

Correlated MeSH Terms (93)


Name (Synonyms) Correlation
D012127 Respiratory Distress Syndrome, Newborn NIH 0.49
D055371 Acute Lung Injury NIH 0.47
D012128 Respiratory Distress Syndrome, Adult NIH 0.44
Name (Synonyms) Correlation
D045169 Severe Acute Respiratory Syndrome NIH 0.17
D018352 Coronavirus Infections NIH 0.16
D054143 Heart Failure, Systolic NIH 0.14
D054058 Acute Coronary Syndrome NIH 0.13
D011665 Pulmonary Valve Insufficiency NIH 0.11
D005356 Fibromyalgia NIH 0.10
D011289 Preleukemia NIH 0.10
D000070627 Chronic Traumatic Encephalopathy NIH 0.10
D001997 Bronchopulmonary Dysplasia NIH 0.10
D008595 Menorrhagia NIH 0.10
D006929 Hyperaldosteronism NIH 0.10
D002561 Cerebrovascular Disorders NIH 0.10
D012778 Short Bowel Syndrome NIH 0.10
D054559 Hyperphosphatemia NIH 0.10
D019462 Syncope, Vasovagal NIH 0.10
D004314 Down Syndrome NIH 0.10
D056587 Cryopyrin-Associated Periodic Syndromes NIH 0.10
D005879 Tourette Syndrome NIH 0.10
D013575 Syncope NIH 0.10
D054144 Heart Failure, Diastolic NIH 0.10
D013616 Tachycardia, Sinus NIH 0.10
D000309 Adrenal Insufficiency NIH 0.10
D007008 Hypokalemia NIH 0.10
D000071257 Emergence Delirium NIH 0.10
D007022 Hypotension NIH 0.10
D006333 Heart Failure NIH 0.09
D055370 Lung Injury NIH 0.07
D011014 Pneumonia NIH 0.07
D003327 Coronary Disease NIH 0.07
D015673 Fatigue Syndrome, Chronic NIH 0.07
D000690 Amyotrophic Lateral Sclerosis NIH 0.07
D000075902 Clinical Deterioration NIH 0.07
D014552 Urinary Tract Infections NIH 0.07
D002546 Ischemic Attack, Transient NIH 0.07
D009190 Myelodysplastic Syndromes NIH 0.07
D000787 Angina Pectoris NIH 0.07
D053201 Urinary Bladder, Overactive NIH 0.07
D000755 Anemia, Sickle Cell NIH 0.07
D001281 Atrial Fibrillation NIH 0.07
D045888 Ganglion Cysts NIH 0.07
D016472 Motor Neuron Disease NIH 0.07
D009410 Nerve Degeneration NIH 0.07
D013610 Tachycardia NIH 0.07
D001714 Bipolar Disorder NIH 0.07
D059350 Chronic Pain NIH 0.06
D020181 Sleep Apnea, Obstructive NIH 0.06
D018746 Systemic Inflammatory Response Syndrome NIH 0.06
D009080 Mucocutaneous Lymph Node Syndrome NIH 0.06
D012640 Seizures NIH 0.06
D011654 Pulmonary Edema NIH 0.06
D016584 Panic Disorder NIH 0.06
D007249 Inflammation NIH 0.05
D001927 Brain Diseases NIH 0.05
D012818 Signs and Symptoms, Respiratory NIH 0.05
D001289 Attention Deficit Disorder with Hyperactivity NIH 0.05
D012891 Sleep Apnea, NIH 0.05
D024821 Metabolic Syndrome NIH 0.05
D012859 Sjogren's Syndrome NIH 0.05
D006470 Hemorrhage NIH 0.05
D009203 Myocardial Ischemia NIH 0.05
D003693 Delirium NIH 0.04
D009102 Multiple Organ Failure NIH 0.04
D058186 Acute Kidney Injury NIH 0.04
D010300 Parkinsonian NIH 0.04
D015212 Inflammatory Bowel Diseases NIH 0.04
D003324 Coronary Artery Disease NIH 0.04
D014947 Wounds and Injuries NIH 0.04
D000070642 Brain Injuries, Traumatic NIH 0.03
D011024 Pneumonia, Viral NIH 0.03
D007239 Infection NIH 0.03
D004194 Disease NIH 0.03
D003424 Crohn Disease NIH 0.03
D001930 Brain Injuries, NIH 0.03
D003141 Communicable Diseases NIH 0.03
D006331 Heart Diseases NIH 0.03
D012598 Scoliosi NIH 0.03
D009103 Multiple Sclerosis NIH 0.03
D020141 Hemostatic Disorders NIH 0.03
D001778 Blood Coagulation Disorders NIH 0.03
D012120 Respiration Disorders NIH 0.03
D016638 Critical Illness NIH 0.02
D007251 Influenza, Human NIH 0.02
D008171 Lung Diseases, NIH 0.02
D014777 Virus Diseases NIH 0.02
D006973 Hypertension NIH 0.02
D012140 Respiratory Tract Diseases NIH 0.02
D002318 Cardiovascular Diseases NIH 0.02
D040921 Stress Disorders, Traumatic NIH 0.02
D012141 Respiratory Tract Infections NIH 0.02
D013313 Stress Disorders, Post-Traumatic NIH 0.02

Correlated HPO Terms (38)


Name (Synonyms) Correlation
HP:0010444 Pulmonary insufficiency HPO 0.11
HP:0002905 Hyperphosphatemia HPO 0.10
HP:0006802 Abnormal anterior horn cell morphology HPO 0.10
Name (Synonyms) Correlation
HP:0002900 Hypokalemia HPO 0.10
HP:0011703 Sinus tachycardia HPO 0.10
HP:0000846 Adrenal insufficiency HPO 0.10
HP:0002615 Hypotension HPO 0.10
HP:0000132 Menorrhagia HPO 0.10
HP:0012668 Vasovagal syncope HPO 0.10
HP:0001279 Syncope HPO 0.10
HP:0007354 Amyotrophic lateral sclerosis HPO 0.10
HP:0000859 Hyperaldosteronism HPO 0.10
HP:0001635 Congestive heart failure HPO 0.10
HP:0002090 Pneumonia HPO 0.08
HP:0001649 Tachycardia HPO 0.07
HP:0004757 Paroxysmal atrial fibrillation HPO 0.07
HP:0002326 Transient ischemic attack HPO 0.07
HP:0100598 Pulmonary edema HPO 0.07
HP:0001681 Angina pectoris HPO 0.07
HP:0002863 Myelodysplasia HPO 0.07
HP:0100754 Mania HPO 0.07
HP:0002180 Neurodegeneration HPO 0.07
HP:0012532 Chronic pain HPO 0.06
HP:0001250 Seizure HPO 0.06
HP:0002870 Obstructive sleep apnea HPO 0.06
HP:0001658 Myocardial infarction HPO 0.05
HP:0007018 Attention deficit hyperactivity disorder HPO 0.05
HP:0010535 Sleep apnea HPO 0.05
HP:0001298 Encephalopathy HPO 0.05
HP:0001919 Acute kidney injury HPO 0.04
HP:0001677 Coronary artery atherosclerosis HPO 0.04
HP:0002037 Inflammation of the large intestine HPO 0.04
HP:0100280 Crohn's disease HPO 0.03
HP:0001928 Abnormality of coagulation HPO 0.03
HP:0000822 Hypertension HPO 0.02
HP:0002088 Abnormal lung morphology HPO 0.02
HP:0011947 Respiratory tract infection HPO 0.02
HP:0001626 Abnormality of the cardiovascular system HPO 0.02

Clinical Trials

Navigate: Correlations   HPO

There are 106 clinical trials


1 Clinical Evaluation and Management of Persons With Severe Acute Respiratory Syndrome (SARS)

This study will evaluate and treat people with SARS, a new type of pneumonia (lung infection) originating in China. SARS is caused by a new virus that is easily transmitted from person to person. This study will look at the course of the disease; determine how the virus affects the body and how the body fights the infection; and evaluate diagnostic tests to quickly identify the disease. People 18 years of age and older with probable or suspected SARS may be eligible for this study. Close contacts of patients with SARS, patients who recovered from SARS, and NIH health care workers involved in the care of patients will also be enrolled. Patients with SARS who require hospitalization will be admitted to the NIH Clinical Center. Because SARS spreads easily, hospitalized patients will be in a room by themselves and will not be allowed any visitors. They will not leave their room except for tests, such as x-rays. All participants will have a full medical examination, including a medical history, physical examination, and blood tests. In addition, the participants undergo various tests and procedures as follows: - Probable and suspected SARS patients may be hospitalized or may be seen as outpatients. They are provided the treatment judged best for their disease, usually according to expressed or published recommendations. The best treatment for SARS is not yet known, and there have been no studies evaluating therapies. Outpatients are seen three times a week for 2 weeks, once a week for 4 more weeks, and then at 6 months. Patients have mouth and throat swabs taken three times a week for the first 2 weeks, then once a week for 4 more weeks. Blood is drawn three times a week for the first 2 weeks, then once at weeks 3, 4, and 6. If virus is still detectable after 6 weeks, nose washings and throat swabs are repeated until no virus is detected for 3 weeks in a row. In addition, patients provide urine and stool samples, have a chest x-ray and electrocardiogram, and undergo bronchoscopy and bronchial lavage. For the bronchoscopy, a bronchoscope (pencil-thin flexible tube) is passed into the large airways of the lung, allowing the physician to examine the airways. Cells and secretions from the airways are rinsed from the lung with salt water. A brush the size of a pencil tip is passed through the bronchoscope to scrape cells lining the airways and pieces of tissue are collected for analysis. - Close contacts of patients are evaluated twice a week for 2 weeks, then once a week for 2 more weeks. Blood is drawn at the first visit and then at 1, 2, and 4 weeks. Mouth and throat swabs, nose washings, and sputum collections are done twice a week for 2 weeks, then once a week for 2 more weeks. Urine and stool samples are collected once a week for 4 weeks. If virus from the nose or throat is still detectable after 4 weeks, weekly nose washings and throat swabs continue until no virus is detected for 3 weeks in a row. Blood may also be drawn during the weekly visits. - Recovered SARS patients provide blood, urine, and stool samples and have a mouth and throat swab and nose aspiration to see if the SARS virus is present. For the nasal aspiration, salt water is put in the nose and then suctioned out. Usually, these tests are done only once. If virus is detected, however, the nose washing, throat swabs and blood tests are repeated once a week until no virus is detected for 3 weeks in a row. - Health care workers document their contact with patients, use of isolation procedures and equipment, and any unexpected events that occur during contact. They are evaluated for symptoms of infection and provide a blood sample once a month

NCT00073086
Conditions
  1. Severe Acute Respiratory Syndrome
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

2 The Interaction Between Severe Acute Respiratory Distress Syndrome Viral Proteins and Monocytes

Severe acute respiratory syndrome (SARS) is a new threat to public health since November, 2002. The SARS is highly contagious and is believed to be transmitted by person-to-person through droplet and direct contact. The patients present with fever, chills, cough, myalgia, dyspnea, and diarrhea. The symptoms aggravate in the second week and nearly 40% of the patients develop respiratory failure that requires assisted ventilation. The mortality rate is reported as 6.5%-7%. After several months, the world scientists found the etiology to be a new coronavirus not belonging to the previous coronavirus group I, II and III. The new virus is called SARS associated coronavirus (SARS-CoV). Although the high morbidity and mortality of SARS occurred in adults, there was rare mortality reported in the children. The report from Hong Kong pointed out that the symptoms of SARS in younger children were milder and the clinical course was not as aggressive as in adults. Therefore, the aim of the project is to design the experiment to see the differences of immunological responses to SARS-CoV protein in healthy younger children, teenagers, and adults. The investigators hope that the result could explain the reason for milder disease in younger children and the immunological pathogenesis of SARS.

NCT00172263
Conditions
  1. Severe Acute Respiratory Syndrome
Interventions
  1. Procedure: blood sampling
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

3 A Multi-centre, Double-blinded, Randomized, Placebo-controlled Trial on the Efficacy and Safety of Lopinavir / Ritonavir Plus Ribavirin in the Treatment of Severe Acute Respiratory Syndrome

The study aims to examine whether the combination of Lopinavir/Ritonavir plus Ribavirin for treatment of severe acute respiratory syndrome (SARS) is superior to placebo.

NCT00578825
Conditions
  1. Severe Acute Respiratory Syndrome
Interventions
  1. Drug: Lopinavir / Ritonavir plus Ribavirin
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

Primary Outcomes

Measure: Development of severe SARS

Time: Any time during the acute illness

Secondary Outcomes

Measure: Adverse events

Time: Throughout the illness period

Measure: SARS-CoV Viral load

Time: Throughout the illness period

Measure: Immunological profile

Time: Throughout the illness period
4 An International Observational Study to Characterize Adults Who Are Hospitalized With Influenza or Other Targeted Respiratory Viruses

Following the sudden and unexpected emergence of influenza A(H1N1)pdm09 (2009 H1N1) virus, this observational study was initiated to estimate rates of morbidity and mortality and to examine predictors of severity among participants with 2009 H1N1 infection. In 2011, as surveillance indicated that 2009 H1N1 virus was co-circulating with other seasonal influenza A and B viruses worldwide, the protocol was expanded to include other influenza A subtypes and influenza B viruses. The current version of the protocol (released in August 2013) further broadens the scope of this observational study. With the recognition that novel respiratory viruses other than novel influenza A viruses, e.g., Middle East Respiratory Syndrome Coronavirus (MERS-CoV), could become prevalent and of major public health importance, the objectives of this protocol have been expanded.

NCT01056185
Conditions
  1. Influenza
  2. Novel Respiratory Virus-1 Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV)
  3. Novel Respiratory Virus-2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)
MeSH:Virus Diseases Influenza, Human Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Measure: Death

Time: 60-day period following enrollment

Secondary Outcomes

Measure: Recovery from influenza illness (including days lost from normal activities) duration of hospitalization, days in intensive care, days of mechanical ventilation, days of dialysis, pregnancy outcome

Time: approximately 60 days
5 A Prospective, Multi-center Registry for Patients With Short Bowel Syndrome

This is a global prospective, observational, multi-center registry to evaluate the long-term safety profile for participants with short bowel syndrome (SBS) who are treated with teduglutide in a routine clinical setting. The registry will also evaluate the long-term clinical outcomes in participants with SBS. SBS participants treated and not treated with teduglutide will be enrolled.

NCT01990040
Conditions
  1. Short Bowel Syndrome
MeSH:Short Bowel Syndrome Syndrome

Primary Outcomes

Description: Incidence rates of colorectal cancer in participants will be calculated by dividing the number of incident colorectal cancer cases by the total number of person-years observed since beginning treatment with teduglutide.

Measure: Occurrence of Colorectal Cancer in Short Bowel Syndrome (SBS) Participants With a Remnant Colon Currently Being Treated With or Ever Having Been Treated With Teduglutide

Time: 10 years

Secondary Outcomes

Description: Incidence rates of other malignancies will be calculated by dividing the number of incident cases by the total number of person-years observed since beginning treatment with teduglutide.

Measure: Occurrence of Other Malignancy

Time: 10 years

Description: Incidence rates of benign neoplasia of the GI tract, hepatobiliary system, and pancreas will be calculated by dividing the number of incident cases by the total number of person-years observed since beginning treatment with teduglutide.

Measure: Occurrence of Benign Neoplasia of the Gastrointestinal (GI) tract, Hepatobiliary System, and Pancreas in Participants

Time: 10 years

Description: Incidence rates of colorectal polyps will be calculated by dividing the number of incident cases by the total number of person-years observed since beginning treatment with teduglutide.

Measure: Occurrence of Colorectal Polyps

Time: 10 years

Description: Incidence rates of intestinal obstruction will be calculated by dividing the number of incident cases by the total number of person-years observed since beginning treatment with teduglutide.

Measure: Occurrence of Intestinal Obstruction

Time: 10 years

Description: Incidence rates of pancreatic and biliary disease will be calculated by dividing the number of incident cases by the total number of person-years observed since beginning treatment with teduglutide.

Measure: Occurrence of Pancreatic and Biliary Disease

Time: 10 years

Description: Incidence rates of heart failure and other manifestations of volume overload will be calculated by dividing the number of incident cases by the total number of person-years observed since beginning treatment with teduglutide.

Measure: Occurrence of Heart Failure and Other Manifestations of Volume Overload

Time: 10 years

Description: Incidence rates of allergic/hypersensitivity reactions to teduglutide will be calculated by dividing the number of incident cases by the total number of person-years observed since beginning treatment with teduglutide.

Measure: Occurrence of Allergic/Hypersensitivity Reaction to Teduglutide

Time: 10 years

Description: Incidence rates of other AEs will be calculated by dividing the number of incident cases by the total number of person-years observed since beginning treatment with teduglutide. Incidence rates of other AEs will be calculated by dividing the number of incident cases by the total number of person-years observed since beginning treatment with teduglutide. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product (ICH Guidance E2A 1995). This includes an exacerbation of a pre-existing condition.

Measure: Occurrence of Other Adverse Events (AEs) Potentially Related to Treatment with Teduglutide

Time: 10 years

Description: PS will be measured by parenteral treatment volume (liters/week) and days (days/week) that occurred in the 7 days prior to the visit.

Measure: Actual Volume Change in Parenteral Support (PS)

Time: 10 years

Description: PS will be measured by parenteral treatment volume (liters/week) and days (days/week) that occurred in the 7 days prior to the visit.

Measure: Percentage Volume Change in Parenteral Support (PS)

Time: 10 years

Description: PS will be measured by parenteral treatment volume (liters/week) and days (days/week) that occurred in the 7 days prior to the visit.

Measure: Actual Change in the Number of Days per Week on Parenteral Support (PS)

Time: 10 years

Description: PS will be measured by parenteral treatment volume (liters/week) and days (days/week) that occurred in the 7 days prior to the visit.

Measure: Percentage Change in the Number of Days per Week on Parenteral Support (PS)

Time: 10 years

Description: PS will be measured by parenteral treatment volume (liters/week) and days (days/week) that occurred in the 7 days prior to the visit.

Measure: Percent of Participants Weaning From Parental Support (PS)

Time: 10 years
6 Essential Arterial Hypotension and Allostasis Registry

The essential arterial hypotension and allostasis registry is a prospective, observational research that has the purpose of demonstrating that essential blood pressure (BP) disorders and the associated comorbidities are a result of the inappropriate allostatic response to daily life stress. This required a functioning brain orchestrating the evaluation of the threat and choosing the response, this is a mind-mediated phenomenon. If the response is excessive it contributes to high BP, if deficient to low BP, and the BP itself will identify the allostatic pattern, which in turn will play an important role in the development of the comorbidities. To do so, consecutive patients of any age and gender that visit a cardiologist's office in Medellin, Colombia, are recruited. Individuals are classified according to their arterial BP and allostasis and follow them in time to see what kind of diseases develops the most (including BP) in the follow up according to the categorization of the characteristic chosen and after adjustment for confounder's variables. In addition, stress events with their date are registered. HYPOTHESIS The causes of the diseases are multifactorial. Physical, biochemical, psychological, social, and cultural dimensions of development dynamically interact to shape the health development process. A person´s health depends on their: 1. Biological and physiologic systems 2. External and internal environment (a) physical, b) internal behavioural and arousal state as registered by the brain. 3. Their interaction. The allostatic mechanisms to the internal and external stressors (allostatic load) involves a network composed by: 1. Functional systems; mediated by: 1. The Autonomic Nervous System 2. The endocrine system 3. The immune system 2. Structural changes: whenever the internal and/or external stressors are long lasting and/or strength enough, they may induce changes in: 1. Epigenetic, endophenotypes, polyphenism. 2. Plasticity 3. The interaction between a) and b). The network response do not affect exclusively the BP, propitiating the development of comorbidities, which may prompt strategies for prevention, recognition and ultimately, treatment. The allostatic model defines health as a state of responsiveness. The concept of psycho-biotype: The allostasis is the result of both: biological (allostasis) and psychological (psychostasis) abilities. It is proposed that both components behave in similar direction and magnitude. Immune disorders may be associated with the development of cancer. High BP population has a higher sympathetic and lower vagal tone, this has been associated with a decrease in the immune´s system function. Resources and energy depletion: Terms like weathering have been used to describe how exposures to different allostatic loads gradually scrape away at the protective coating that keeps people healthy. It is postulated that High BP individuals have more resources and energy.

NCT02018497
Conditions
  1. Blood Pressure
  2. Depression
  3. Panic Attack
  4. Fibromyalgia
  5. POTS
  6. Inappropriate Sinus Tachycardia
  7. Coronary Heart Disease
  8. Acute Coronary Syndrome (ACS)
  9. Acute Myocardial Infa
  10. Acute Myocardial Infarction (AMI)
  11. Cerebrovascular Disease (CVD)
  12. Transient Ischemic Attack (TIA)
  13. Atrial Fibrillation
  14. Diabetes Mellitus
  15. Cancer
  16. Systolic Heart Failure
  17. Diastolic Heart Failure
  18. Chronic Fatigue Syndrome
  19. Syncope
  20. Vasovagal Syncope
MeSH:Fatigue Syndrome, Chronic Fibromyalgia Syncope Ischemic Attack, Transient Cerebrovascular Disorders Syncope, Vasovagal Heart Failure Atrial Fibrillation Heart Diseases Myocardial Infarction Acute Coronary Syndrome Hypotension Coronary Disease Tachycardia Heart Failure, Diastolic Heart Failure, Systolic Tachycardia, Sinus Syndrome Panic Disorder
HPO:Atrial fibrillation Carotid sinus syncope Congestive heart failure Hypotension Left ventricular dysfunction Myocardial infarction Paroxysmal atrial fibrillation Right ventricular failure Sinus tachycardia Syncope Tachycardia Transient ischemic attack Vasovagal syncope

Primary Outcomes

Description: Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, and others. Cardiovascular mortality Total mortality

Measure: Relationship between Blood pressure group and comorbidities

Time: A 7-year prospective study

Description: Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, and others. Cardiovascular mortality Total mortality

Measure: Relationship between adaptability group and comorbidities

Time: A 7-year prospective study

Description: Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension. Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, and others. Cardiovascular mortality Total mortality

Measure: Relationship between blood pressure group, adaptability group and comorbidities

Time: A 7-year prospective study

Secondary Outcomes

Description: Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension. Habits: smoke and drink Anthropometric variables: Body mass index, waist, hip Metabolic variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, homoeostasis model assessment (HOMA), total cholesterol, LDL, HDL, triglycerides. Endocrine variables: plasma cortisol, free cortisol in 24 hs. urine, epinephrine, norepinephrine, metanephrines, vanilmandelic acid, ACTH, aldosterone, renin, thyrotropine, free thyroxine, triiodothyronine, testosterone Electrocardiogram: HR; PR interval, QRS complex, cQT interval Holter variables: HR, standard deviation of NN intervals (SDNN) and sympathovagal balance, at day, night and 24 hs. ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.

Measure: Relationship between blood pressure group, habits and anthropometric, metabolic, endocrine, Electrocardiogram, Holter, ambulatory blood pressure monitoring (ABPM)

Time: A 7-year prospective study

Description: Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension. Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Habits: smoke and drink Anthropometric variables: Body mass index, waist, hip Metabolic variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, HOMA, total cholesterol, LDL, HDL, triglycerides. Endocrine variables: plasma cortisol, free cortisol in 24 hs. urine, epinephrine, norepinephrine, metanephrines, vanilmandelic acid, ACTH, aldosterone, renin, thyrotropine, free thyroxine, triiodothyronine, testosterone Electrocardiogram: PR interval, QRS complex, Heart rate, cQT interval Holter variables: HR, SDNN and sympathovagal balance, at day, night and 24 hs. ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.

Measure: Relationship between blood pressure group, adaptability group, habits anthropometric, metabolic, endocrine, electrocardiographic, Holter, ambulatory arterial blood pressure monitoring.

Time: A 7-year prospective study

Description: Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension. Adaptability group: 1) Hyper adaptable, 2) normal adaptability and 3) hypo adaptable. Habits: smoke and drink, exercise Anthropometric variables: Body mass index, waist, hip Metabolic and other variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, HOMA, total cholesterol, LDL, HDL, triglycerides; thyrotropine, Holter variables: HR, standard deviation of NN intervals (SDNN) and sympathovagal balance, at day, night and 24 hs. ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.

Measure: For metabolic disorders what it matters the most: the anthropometric variables vs blood pressure group vs adaptability group

Time: A 7-year prospective study

Description: Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Habits: smoke and drink Anthropometric variables: Body mass index, waist, hip Metabolic variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, HOMA, total cholesterol, LDL, HDL, triglycerides. Endocrine variables: plasma cortisol, free cortisol in 24 hs. urine, epinephrine, norepinephrine, metanephrines, vanilmandelic acid, ACTH, aldosterone, renin, thyrotropine, free thyroxine, triiodothyronine, testosterone Electrocardiogram: PR interval, QRS complex, Heart rate, cQT interval Holter variables: HR, SDNN and sympathovagal balance, at day, night and 24 hs. ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.

Measure: Relationship between adaptability group, habits and anthropometric, metabolic, endocrine, Electrocardiogram, Holter, ambulatory blood pressure monitoring (ABPM)

Time: A 7-year prospective study

Other Outcomes

Description: Clinical syncope characteristics (age of first syncope, number of syncope episodes, trauma, duration, clinical score, convulse, sphincter relaxation, etc.) Syncope cause Blood pressure group Adaptability group Prognosis

Measure: Syncope Registry

Time: Up 100 weeks

Description: TTT protocol: describe the protocol, the time at positive response, nitroglycerine use, autonomic and hemodynamic variables. TTT outcome for syncope: positive or negative TTT other outcomes: 1) Chronotropic incompetence, 2) arterial orthostatic hypotension, 3) carotid hypersensitivity, 4) POTS, 5) IST The relationship between TTT results and Clinical score for syncope in regard to: syncope behaviour and other orthostatic intolerance entities, symptoms and comorbidities. The relationship between neurally mediated syncope response at the TTT and comorbidities.

Measure: Tilt table testing (TTT) registry

Time: Up to 100 weeks

Description: EPS variables: AH, AV, CL, sino atrial conduction time (SACT), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), response to Isoproterenol, intrinsic heart rate Diagnosis: control, sick sinus syndrome, IST, chronotropic incompetence at the TTT HR at the ECG HR at the Holter monitoring HR at the TTT HRV at the Holter monitoring Syncope, cardiac or neurally mediated HR at the physical treadmill test Relationship with the blood pressure group Relationship with the adaptability group

Measure: Sinus node function at the electrophysiological study (EPS)

Time: Up to 100 weeks

Description: Define how the blood pressure group and/or the adaptability group may add to the already known and include in this registry, in the diagnosis of cardiovascular complications as coronary artery disease, cerebrovascular disease, peripheral artery disease, nephropathy.

Measure: Score for coronary artery disease

Time: Up to 200 weeks

Description: Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension. Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, COPD, and others. Mortality

Measure: Neurally Mediated Syncope: further of the transient lost of consciousness (TLC)

Time: A 7-year prospective study

Description: Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension. Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Psychiatric variables: Big Five Questionary (BFQ) for personality. Modify of the Coping Scale (Scale of modified coping strategies) Zung questionary for depression and anxiety MINI in those patients with moderate or severe depression and/or anxiety at the Zung questionary

Measure: Psychobiotype: relationship between biological and psychological variables

Time: Up to 100 weeks

Description: High sodium intake in the diet is recognized as a risk factor for hypertension development. Essential hypotension population is advised to increase the sodium (at least 10 grams a day) and water intake (at least 2 liters a day), or as much as possible, several have taken Fludrocortisone (is not a exclusion criteria). Normal blood pressure population are advised to have a normal or low sodium intake. Physical exercise is recommended in both groups. This registry is a good opportunity to test how important sodium diet is to induce hypertension, or if by the contrary adaptability could prevail over high sodium intake in this registry. Blood pressure groups: essential hypotension and normotension and those with new essential hypertension. Adaptability groups. The results will be adjusted for age, gender and BMI.

Measure: The role of high sodium intake in the development of essential hypertension. Comparison between essential hypotension (high sodium intake) vs normotension population (normal or low sodium intake) in the follow-up.

Time: 4 years

Description: Consistent bradycardia in the ECG at the office and normal HR in the holter monitoring or the contrary. There are patients with complaints that may be attributed to bradycardia, low blood pressure, hypothyroidism, or other entities. Some patients very often have bradycardia in the ECG taken in the office and normal HR in the 24 Holter monitoring, the opposite is also possible. Patients with bradycardia (without medication or physiological condition as exersice affecting heart rate) in at least 2 ECG (less 60 bpm) and at least 2 Holter monitoring will be analyzed, Other variables to consider are: Age, gender, blood pressure group, adaptability group, maximum HR in the treadmill test, white coat or masked hypertension, Tilt-Table-test result or syncope cause, Electrophysiological study if available. The acknowledge of this phenomenon could have clinical implications in the diagnosis of sick sinus syndrome and physiopathological ones.

Measure: White coat effect in the heart rate or masked bradycardia.

Time: 1 year

Description: Bradycardia is the classical presentation form for sinus node dysfunction, mainly when associated with symptoms. Chronotropic incompetence is also a manifestation. Absence of medications with effects on the heart rate (HR) must be ruled out. Variables HR at the ECG, Holter monitoring, stress text, and at the physical examination previous to pacemaker implantation, Electrophysiological study (EPS): Basic cycle length, Sino-atrial conduction time, Sinus node recovery time, Corrected sinus node recovery time, Intrinsic HR when available 3. Pacemaker variables: HR at day and night or rest time Percentage of stimulation in A and V chambers 4. Syncope: Clinical characteriscs and clinical score Tilt table test results Trans Thoracic Echocardiogram in rest and or stress text Hypothesis: patients with ANSD will start to decrease the percentage atrial stimulation.

Measure: Reversible Bradycardia Mimicking Sinus Node Dysfunction as a Manifestation of Subacute Autonomic Nervous System Dysfunction (ANSD).

Time: 2 years

Description: A non invasive, beat to beat BP monitoring, with the ability to measure BP, HR, Cardiac Output and Systemic Vascular Resistance (SVR) was started to use in the EHAR registry since May 2017. A description of this variables in the three BP groups will be collected in the data base (DB). This will allow to characterize whether SVR and/or CO maintain BP. Until now BP levels are related with prognosis. In the prognosis model SVR and CO will be add them to know what matter the most: BP levels, SVR and/or CO? In the EHAR registry a collection of the variables recognized as a risk factor for several comorbidities are available to adjust in multivariable analysis.

Measure: Description of the blood pressure hemodynamic profile at a medical office and their prognostic implications.

Time: Three years
7 Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST): An Open Label Dose Escalation Phase 1 Trial Followed by a Randomized, Double-blind, Placebo-controlled Phase 2 Trial (COVID-19)

Acute Respiratory Distress Syndrome (ARDS) causes the lungs to fail due to the collection of fluid in the lungs (pulmonary oedema). ARDS is common in severely ill patients in Intensive Care Units and is associated with a high mortality and a high morbidity in those who survive. ARDS occurs in approximately 20% case of COVID-19 and respiratory failure is the leading cause of mortality. There is a large economic burden with direct healthcare costs, but also indirectly due to the impact on the carer and patient through the patients inability to return to full time employment. There is little evidence for effective drug (pharmacological) treatment for ARDS. There is increasing information that mesenchymal stem cells (MSCs) might be important in treating ARDS. REALIST will investigate if a single infusion of MSCs will help in the treatment of ARDS. The first step will be to first of all determine what dose of MSCs is safe and then divide patients suffering from ARDS into two groups, one of which will get MSCs and the other a harmless dummy (or placebo) infusion, who will then be followed up to determine if lung function improves. If effective this may lead to further research to determine if MSCs are effective in patients with ARDS.

NCT03042143
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Human umbilical cord derived CD362 enriched MSCs
  2. Biological: Placebo (Plasma-Lyte 148)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: OI is a physiological index of the severity of ARDS and measures both impaired oxygenation and the amount of mechanical ventilation delivered

Measure: Oxygenation index (OI)

Time: Day 7

Description: Incidence of SAEs

Measure: Incidence of Serious Adverse Events (SAEs)

Time: 28 days

Secondary Outcomes

Measure: Oxygenation index

Time: Days 4 and 14

Description: SOFA score is a measure of organ failure

Measure: Sequential Organ Failure Assessment (SOFA) score

Time: Days 4, 7 and 14

Description: Crs is a physiological measure of pulmonary function in ARDS

Measure: Respiratory compliance (Crs)

Time: Days 4, 7 and 14

Description: P/F ratio is a physiological measure of pulmonary function in ARDS

Measure: Partial pressure of arterial oxygen to the fraction of inspired oxygen ratio (P/F ratio)

Time: Days 4, 7 and 14

Measure: Driving Pressure

Time: Days 4, 7 and 14

Measure: Extubation and reintubation

Time: Up to day 14 or until the patient is discharged from ICU or the patient dies

Measure: Ventilation free days at day 28

Time: Day 28

Measure: Length of ICU and hospital stay

Time: Until the patient is discharged or the patient dies

Measure: 28-day and 90-day mortality

Time: Up to 28 and 90 days
8 Implementation of Lung Protective Ventilation in Patients With Acute Respiratory Failure

This is a quality improvement study with the purpose of observing and measuring the effects of implementation of a proven standardized lung protective ventilation protocol in the new electronic medical record system iCentra across all Intermountain Healthcare hospitals. Approximately 14,000 records will be accessed for this study from a database of mechanically ventilated patients established for quality improvement purposes. The investigators hypothesize that implementation of a standardized computerized lung protective ventilation protocol across all Intermountain Healthcare hospitals will be feasible, will decrease initial tidal volumes to the target 6 ml/kg PBW, and will improve outcomes. The objectives of this study are to: - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in patients with acute respiratory failure requiring mechanical ventilation - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in the sub-group of patients with the acute respiratory distress syndrome (ARDS) - Measure compliance with the implementation of a computerized lung protective ventilation protocol at 12 Intermountain Healthcare hospitals

NCT03225807
Conditions
  1. Acute Respiratory Distress Syndrome
  2. ARDS
  3. Respiratory Distress Syndrome, Acute
  4. Respiratory Insufficiency
  5. Respiratory Distress Syndrome
  6. Shock Lung
  7. Severe Acute Respiratory Syndrome
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Pulmonary Valve Insufficiency Syndrome
HPO:Pulmonary insufficiency

Primary Outcomes

Measure: Ventilator free days to day 28

Time: 28 days

Secondary Outcomes

Measure: 30 day mortality

Time: 30 days

Measure: 90 day mortality

Time: 90 days

Measure: Hospital discharge disposition

Time: 30 days

Measure: Hospital mortality

Time: 1 week

Measure: Time to first ICU activity

Time: 24 hours
9 A Phase I Study to Determine the Safety and Immunogenicity of the Candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Vaccine ChAdOx1 MERS in UK Healthy Adult Volunteers

This is a clinical trial in which healthy volunteers will be administered an experimental MERS vaccine. The vaccine ChAdOx1 MERS will be administered alone both as a single administration and with a homologous prime-booster.

NCT03399578
Conditions
  1. MERS (Middle East Respiratory Syndrome)
Interventions
  1. Biological: ChAdOx1 MERS
MeSH:Coronavirus Infections Syndrome

Primary Outcomes

Description: The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. Change from baseline for safety laboratory measures will also be collected. Occurrence of serious adverse events will be collected during the whole study duration

Measure: Occurrence of solicited and unsolicited local and systemic adverse events

Time: up to 28 days following vaccination

Secondary Outcomes

Description: ELISA to quantify antibodies to MERS Spike protein antigen Ex vivo ELISpot responses to MERS Spike protein antigen

Measure: Measures of immunogenicity to the ChAdOx1 MERS vaccine

Time: 12 months
10 Streptokinase Versus Unfractionated Heparin Nebulization in Patients With Severe Acute Respiratory Distress Syndrome (ARDS): A Partially Randomized Controlled Trial

Background: Intra-alveolar clotting and alveolar collapse in ARDS is due to alveolar capillaries epithelial and leakage. Subsequently, collapse induces hypoxemia that is resistant to recruitment (RM). Heparin and Streptokinase may prevent or dissolve intra-alveolar fibrin clot respectively helping alveolar re-expansion. We examined and compared the effect of nebulizing Heparin versus Streptokinase on reversing this pathology. Methods: Sixty severe ARDS (PaO2/FiO2<100) patients and failure of RM, prone position (PP) and neuromuscular block (NMB) were partially randomised into Group (I): (n=20) received nebulized Heparin 10000 IU/4h. Group (II): (n=20) received nebulized Streptokinase 250,000 IU/4h. Group (III): (n=20) received conservative management. Randomization to either Heparin or Streptokinase groups was applied to patients whom guardian accepted participation, while those who declined participation were followed-up as a control. The primary outcome was the change in PaO2/FiO2; the secondary outcomes included the change in compliance, plateau pressure, ventilation-off days, coagulation and ICU mortality.

NCT03465085
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Severe Acute Respiratory Syndrome
Interventions
  1. Drug: Unfractionated heparin
  2. Drug: Streptokinase
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Dis Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Change in the ratio of arterial oxygen tension to fraction of inspired oxygen from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.

Measure: Change in PaO2/FiO2 ratio

Time: daily over eight days

Secondary Outcomes

Description: Change in the plateau airway pressure during ventilation from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.

Measure: Change in the plateau pressure

Time: daily over eight days

Description: change in volume of the lungs per change in pressure during ventilation from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.

Measure: Change in the pulmonary compliance

Time: daily over eight days

Description: Number of patients who are discharged alive

Measure: ICU survival rate

Time: At the end of ICU stay up to one year after the start of recruitment

Description: the total duration the patient stays in ICU

Measure: ICU length of stay

Time: At the end of ICU stay up to one year after the start of recruitment

Description: number of patients who required tracheostomy

Measure: Tracheostomy rate

Time: During ICU stay up to one month after the start of recruitment
11 Incobotulinumtoxin Versus Onabotulinumtoxin in the Treatment of Patients With Overactive Bladder Syndrome

The aim of the original study was to compare Incobot/A versus Onabot/A in order to evaluate if the differences in the pharmacologic formulations between the two drugs could affect their efficacy and safety in the treatment of neurogenic overactive bladder (OAB). In the original study protocol two different dosages for either Incobot/A and Onabot/A (200 U and 100 U) were considered, to treat patients with neurogenic detrusor overactivity incontinence performing intermittent catheterization (IC) with higher dosages and those able to void spontaneously with lower dosage, with the resulting four treatment groups. For such a study, a very large sample of participants should have been treated and followed up, to have adequate power to demonstrate the hypothesis. At the end of last February 2020, we had to temporarily stop all the clinical activities related to the study and patients' recruitment, due to the occurrence of Sars-Cov-2 pandemic in our Country. At that point, a non-inferiority study seemed to be possible and adequate, and we adapted the protocol accordingly. In addition, on the basis of previously published information, we could hypothesize that the new drug (Incobot/A) would have had at least a roughly similar effect to the control drug (Onabot/A). In order to perform a non-inferiority study, the power and sample size analysis have been re-planned. Thus, we perform a not planned interim analysis to show the preliminary results of an ongoing, non-inferiority trial in which patients' recruitment temporarily stopped due to incontrollable external factors. The present study will be aimed to assess the non-inferiority of Incobot/A compared to Onabot/A on the efficacy and safety parameters, in the treatment of patients with refractory NDOI performing IC, who are randomized to receive 200 U of Incobot/A or Onabot/A intradetrusor injections and who are followed up to 12 wks after treatment

NCT03758235
Conditions
  1. Overactive Bladder Syndrome
Interventions
  1. Drug: IncobotulinumtoxinA 100 UNT Injection [Xeomin]
  2. Drug: OnabotulinumtoxinA 100 UNT [Botox]
MeSH:Urinary Bladder, Overactive Syndrome

Primary Outcomes

Description: change from baseline in the daily frequency of urinary incontinence episodes, as assessed by the 3-day voiding diary.

Measure: Change from baseline in the frequency of urinary incontinence episodes.

Time: 24 weeks

Description: Measurement of eventual differencies between the two arms of treatment in the frequency of urinary tract infections at 2, 12 and 24 weeks after treatment

Measure: Evaluation of frequency of urinary tract infections in both arms of treatment.

Time: 2, 12, 24 weeks

Secondary Outcomes

Description: Significant improvements in urodynamic parameters (maximum cystometric capacity, maximum detrusor pressure during first involuntary detrusor contraction) at 12 and 24 weeks as compared to baseline.

Measure: Change from baseline in urodynamic parameters.

Time: 24 weeks

Description: Significant improvement in I-QoL total score at 2, 12 and 24 weeks as compared to baseline.

Measure: Change from baseline in Incontinence Quality of Life (I-QoL) questionnaire total score.

Time: 2, 12, 24 weeks

Description: Assessment of possible adverse events-AE (systemic AEs: fatigue, weakness, dyspnoea, gastrointestinal irritation, Flu-like symptoms, dizziness; local AEs: haematuria, dysuria, urinary retention, post-void residual volume > 150 ml) at 2, 12 and 24 weeks after treatment.

Measure: Recording of the adverse events.

Time: 2, 12, 24 weeks
12 An Open-label, Standard Therapy as a Controlled, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of HLCM051(MultiStem) in Patients With Acute Respiratory Distress Syndrome (ARDS) Caused by Pneumonitis

The primary object of this clinical study is to investigate the efficacy of HLCM051 in patients with ARDS caused by pneumonitis.

NCT03807804
Conditions
  1. Respiratory Distress Syndrome, Adult
Interventions
  1. Biological: HLCM051
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: VFD for 28 days after administration of the investigational product

Measure: Ventilator-free days (VFD)(ARDS caused by pneumonia cohort)

Time: 28 days after administration of the investigational product

Description: The number and rate of adverse events

Measure: Adverse events(ARDS caused by COVID-19 cohort)

Time: From informed consent to 180 days after administration of the investigational product

Description: Change from baseline in systolic blood pressure(mmHg)

Measure: Change from baseline in systolic blood pressure(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in diastolic blood pressure(mmHg)

Measure: Change from baseline in diastolic blood pressure(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in pulse rate(beats/min)

Measure: Change from baseline in pulse rate(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in respiration(breath/min)

Measure: Change from baseline in respiration(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in oxygen saturation(%)

Measure: Change from baseline in oxygen saturation(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in body temperature(C)

Measure: Change from baseline in body temperature(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in red blood cell count(/uL)

Measure: Change from baseline in red blood cell count(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in hemoglobin(g/dL)

Measure: Change from baseline in hemoglobin(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in hematocrit(%)

Measure: Change from baseline in hematocrit(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in leukocyte count(/uL)

Measure: Change from baseline in leukocyte count(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in neutrophils(%)

Measure: Change from baseline in neutrophils(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in eosinophils(%)

Measure: Change from baseline in eosinophils(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in basophils(%)

Measure: Change from baseline in basophils(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in lymphocytes(%)

Measure: Change from baseline in lymphocytes(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in monocytes(%)

Measure: Change from baseline in monocytes(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in platelet count(/uL)

Measure: Change from baseline in platelet count(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in asparate aminotransferase(AST)(IU/L)

Measure: Change from baseline in asparate aminotransferase(AST)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in alanine aminotransferase(ALT)(IU/L)

Measure: Change from baseline in alanine aminotransferase(ALT)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in alkaline phosphatase(ALP)(IU/L)

Measure: Change from baseline in alkaline phosphatase(ALP)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in total bilirubin(mg/dL)

Measure: Change from baseline in total bilirubin(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in blood urea nitrogen(BUN)(mg/dL)

Measure: Change from baseline in blood urea nitrogen(BUN)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in creatinine(mg/dL)

Measure: Change from baseline in creatinine(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in sodium(Na)(mmol/L)

Measure: Change from baseline in sodium(Na)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in potassium(K)(mmol/L)

Measure: Change from baseline in potassium(K)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in chloride(Cl)(mmol/L)

Measure: Change from baseline in chloride(Cl)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in calcium(Ca)(mg/dL)

Measure: Change from baseline in calcium(Ca)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in blood sugar(mg/dL)

Measure: Change from baseline in blood sugar(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in urinary protein(- to >= 4+)

Measure: Change from baseline in urinary protein(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in urinary sugar(- to >= 4+)

Measure: Change from baseline in urinary sugar(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in uric blood(- to >= 4+)

Measure: Change from baseline in uric blood(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in urinary sediment(RBC)(/HPF)

Measure: Change from baseline in urinary sediment(RBC)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in urinary sediment(WBC)(/HPF)

Measure: Change from baseline in urinary sediment(WBC)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product

Description: Change from baseline in urinary sediment(Other)(/HPF)

Measure: Change from baseline in urinary sediment(Other)(ARDS caused by COVID-19 cohort)

Time: From screening to 180 days after administration of the investigational product
13 Outcomes Mandate National Integration With Cannabis as Medicine for Prevention and Treatment of COVID-19

This will be a multistate, multicenter clinical study to determine the efficacy and safety of medical cannabis for a wide variety of chronic medical conditions.

NCT03944447
Conditions
  1. Chronic Pain
  2. Chronic Pain Syndrome
  3. Chronic Pain Due to Injury
  4. Chronic Pain Due to Trauma
  5. Fibromyalgia
  6. Seizures
  7. Hepatitis C
  8. Cancer
  9. Crohn Disease
  10. HIV/AIDS
  11. Multiple Sclerosis
  12. Traumatic Brain Injury
  13. Sickle Cell Disease
  14. Post Traumatic Stress Disorder
  15. Tourette Syndrome
  16. Ulcerative Colitis
  17. Glaucoma
  18. Epilepsy
  19. Inflammatory Bowel Diseases
  20. Parkinson Disease
  21. Amyotrophic Lateral Sclerosis
  22. Chronic Traumatic Encephalopathy
  23. Anxiety
  24. Depression
  25. Insomnia
  26. Autism
  27. Opioid-use Disorder
  28. Bipolar Disorder
  29. Covid19
  30. SARS-CoV Infection
  31. COVID-19
  32. Corona Virus Infection
  33. Coronavirus
Interventions
  1. Drug: Cannabis, Medical
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Fibromyalgia Crohn Disease Inflammatory Bowel Diseases Parkinson Disease Multiple Sclerosis Brain Injuries Brain Injuries, Traumatic Seizures Moto Motor Neuron Disease Amyotrophic Lateral Sclerosis Brain Diseases Tourette Syndrome Chronic Traumatic Encephalopathy Anemia, Sickle Cell Disease Syndrome Sclerosis Chronic Pain Wounds and Injuries Stress Disorders, Traumatic Bipolar Disorder Stress Disorders, Post-Traumatic
HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis Bilateral tonic-clonic seizure Bipolar affective disorder Chronic pain Crohn's disease Encephalopathy Focal-onset seizure Generalized-onset seizure Inflammation of the large intestine Mania Seizure

Primary Outcomes

Description: Covid-19 infection rates in cannabis users will be compared to rates in the general population. Our online questionnaire responses will compare infection rates of cannabis users in this study against the Johns Hopkins University Coronavirus Research Center data (https://coronavirus.jhu.edu).

Measure: Prevention of COVID-19

Time: Five years

Description: Severity of persistent symptoms in cannabis users testing positive for active infection and/or antibodies will also be compared to the general population. Patients will answer the widely used FLU-PRO questionnaire, which asks about flu symptoms and severity, to capture diagnoses, symptoms, and medical interventions related to COVID-19. The data from cannabis user patients will be compared with national and international data surveys, such as the Covid Symptom Study (https://covid.joinzoe.com/us-2).

Measure: Treatment of COVID-19

Time: Five years

Description: The primary objective is to assess the efficacy and safety of medical cannabis as medicine for treatment of chronic pain and other chronic debilitating diseases. Pain will be measured by Brief Pain Inventory (BPI) numeric scale. Change from baseline in BPI will be assessed at 3-month intervals. For prospective associations between cannabis use and outcomes, use of a lagged mixed-effects models will examine temporal associations between cannabis use and pain severity, opioid sparing, and patient satisfaction. Data will be analyzed from baseline and the annual follow-up waves.

Measure: Treatment of Symptoms

Time: Five years

Secondary Outcomes

Description: Secondary objectives include evaluating increases or decreases in quality of life, and increases or decreases in concomitant opioid use. Satisfaction with treatment will be measured by a Visual Analog Score (VAS). Change From baseline in Satisfaction with treatment measured by (VAS) be assessed at 3-month intervals.

Measure: Cannabis Impact on Quality of Life

Time: Five years

Description: Tertiary objectives will examine preferences for routes of administration, and preferences for THC / CBD ratios. Categorical factors will be summarized using frequencies and percentages, while continuous measure distributions will be described using means, standard deviations, and quartiles of interest.

Measure: Cannabis Route and Dosing

Time: Five years

Description: Incidence of Treatment-Related Adverse Events will be measured by Physician Global Assessment (PGA) numeric scale. Number of participants with Treatment-Related Adverse Events will be assessed by CTCAE v4.0.

Measure: Monitoring Adverse Events

Time: Five years
14 Developing a Positive Psychology Intervention to Promote Health Behaviors in Metabolic Syndrome: A Randomized Controlled Pilot Trial

Specific Aim #1 (Feasibility; primary aim): To assess the feasibility of the PP-MI group-based physical activity intervention and outcome assessments in patients with MetS. Hypothesis: The PP exercises and MI-based goal-setting sessions will be feasible: most (≥50%) of participants will complete 6/9 exercises/sessions. Furthermore, the investigators will be able to obtain objective physical activity measurement follow-up data from at least 80% of enrolled participants at the end of the intervention and 24 weeks later. Specific Aim #2 (Acceptability): To assess whether the intervention is acceptable to participants, as measured by ratings provided after each PP-MI session. Hypothesis: The intervention will be acceptable: participants will rate the PP-MI exercises with a mean score of at least 7 out of 10 on ease of completion and helpfulness. Specific Aim #3 (Outcomes): To assess whether this preliminary intervention appears to result in improvement of physical activity, related health behaviors (sedentary time, diet quality), psychological well-being (optimism, positive affect, anxiety, depression), and the exploratory outcomes of MetS-relevant physiological markers (e.g., blood pressure, weight, chart-reviewed lipids and HbA1C). Hypothesis a: The intervention will lead to improvements in physical activity, related health behaviors, optimism and positive affect, reductions in depression and anxiety at 9 weeks and 24 weeks compared to baseline (or the start of the intervention, for the WLC group). Hypothesis b: The hypothesis is that there will be improvements in the exploratory outcomes of the physiological markers, even if they do not reach significance.

NCT04039165
Conditions
  1. Metabolic Syndrome
Interventions
  1. Behavioral: PP-MI Intervention
MeSH:Metabolic Syndrome Syndrome

Primary Outcomes

Description: Feasibility will be measured by examining the number of completed exercises.

Measure: Feasibility of the PP-MI-Based Health Behavior Intervention

Time: 8 weeks of group sessions

Secondary Outcomes

Description: Participants will rate the ease and usefulness of each weekly activity (0-10).

Measure: Acceptability of Intervention

Time: 8 weeks

Description: ActiGraph GT3X+ accelerometers are validated as measures of physical activity and have been used in numerous studies of physical activity in patients with medical illness. In this trial, participants will wear the accelerometer to assess the feasibility of doing so and to ensure adequate capture of physical activity.

Measure: Physical Activity Adherence (Actigraph)

Time: Baseline, weeks 9, 24 (baseline, weeks 9, 17, 33 for the WLC group)

Description: Feasibility will be measured by examining the rates of use of the Actigraph.

Measure: Feasibility of Actigraph

Time: Baseline, weeks 9, 24 (baseline, weeks 9, 17, 33 for the WLC group)

Description: The LOT-R is a well-validated 6-item instrument used to measure dispositional optimism. (Range: 5-30)

Measure: Changes in Life Orientation Test- Revised Scores

Time: Baseline, weeks 9, 24 (Baseline, weeks 17 and 33 for the WLC group)

Description: The positive affect items on the Positive and Negative Affect Schedule (PANAS), a well-validated scale used in other intervention trials, will be used to measure positive affect. (Range: 10-50)

Measure: Changes in Positive and Negative Affect Schedule Scores

Time: Baseline, weeks 9, 24 (Baseline, weeks 17 and 33 for the WLC group)

Description: The HADS will be used to measure depression and anxiety. This is a well-validated scale with few somatic symptom items that can confound mood/anxiety assessment in medically-ill patients. (Range: HADS-A, HADS-D; 0-21 each)

Measure: Changes in The Hospital Anxiety and Depression Scale Scores

Time: Baseline, weeks 9, 24 (Baseline, weeks 17 and 33 for the WLC group)

Description: The BBAQ is a 21-item measure, published by the US Centers for Disease Control and Prevention (CDC), that explores seven main categories of barriers, including lack of time, energy, and resources. (Range: 0-63)

Measure: Changes in Barriers to Being Active Quiz Scores

Time: Baseline, weeks 9, 24 (Baseline, weeks 17 and 33 for the WLC group)

Description: The SOM will be used to capture the changeable nature of optimism based on time and situation. (Range: 7-35)

Measure: Changes in State Optimism Measure

Time: Baseline, weeks 9, 24 (Baseline, weeks 17 and 33 for the WLC group)

Description: The SF-12 will be used to measure quality of life. This instrument has been used in many patient-oriented studies. (Range: SF-12 PCS and SF-12 MCS); range 0-100 each)

Measure: Changes in The Medical Outcomes Study Short Form-12 Scores

Time: Baseline, weeks 9, 24 (Baseline, weeks 17 and 33 for the WLC group)

Description: The IPAQ-SF is a validated scale that measures self-reported physical activity in the past 7 days in the domains of vigorous activity, moderate activity, and walking.

Measure: Changes in The International Physical Activity Questionnaire-Short Form Scores

Time: Pre-baseline screening, weeks 9, 24 (Pre-baseline, weeks 17 and 33 for the WLC group)

Description: The CDC's BRFSS Fruit and Vegetable Module is a brief questionnaire about frequency of eating different types of fruits and vegetables.

Measure: Changes in Behavioral Risk Factor Surveillance System Fruit and Vegetable Module

Time: Baseline, weeks 9, 24 (Baseline, weeks 17 and 33 for the WLC group)

Description: The National Cancer Institute's Percentage Energy from Fat Screen is a brief questionnaire that estimates people's typical percentage of energy derived from eating common fat-containing foods, as fat content is related to metabolic syndrome progression.

Measure: Changes in National Cancer Institute's Percentage Energy from Fat Screener Scores

Time: Baseline, weeks 9, 24 (Baseline, weeks 17 and 33 for the WLC group)
15 Double-blind, Placebo-controlled Study With an Open Dose Selection Period for Assessing the Safety and Immunogenicity of the Drug "BVRS-GamVac-Combi", a Combined Vector Vaccine for the Prevention of the Middle East Respiratory Syndrome, Lyophilisate for the Preparation of a Solution for Intramuscular Administration, With the Participation of Healthy Volunteers

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreak. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~34.5%. The aim of the study is to assess the safety and immunogenicity of heterologous adenoviral-based vaccine against MERS - BVRS-GamVac-Combi.

NCT04128059
Conditions
  1. MERS (Middle East Respiratory Syndrome)
  2. MERS
Interventions
  1. Drug: BVRS-GamVac-Combi
  2. Other: placebo
MeSH:Coronavirus Infections Syndrome

Primary Outcomes

Description: Determination of Number of Participants With Adverse Events

Measure: Number of Participants With Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of Number of Participants With Serious Adverse Events

Measure: Number of Participants With Serious Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of Number of Participants with Solicited Local and Systemic Adverse Events

Measure: Number of Participants with Solicited Local and Systemic Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of antibody levels against the MERS-CoV glycoprotein S measured by an ELISA vs. baseline values (phase 1, phase 2) and placebo (phase 2)

Measure: Antibody levels against the MERS-CoV glycoprotein S measured by an enzyme-linked immunosorbent assay (ELISA)

Time: Time Frame for group 1 phase 1: at days 0, 7, 14, 21, 28, 42, 56 and 90. Time Frame for group 2 phase 1 and phase 2: at days 0, 7, 14, 21, 28, 35, 42, 56 and 90

Secondary Outcomes

Description: determination of specific T-cell- mediated response vs. baseline values and placebo

Measure: Assessment of antigen-specific cell-mediated immune response

Time: at 0, 14 and 28 days from the start of vaccination compared to baseline values (phase 1, phase 2) and placebo (phase 2)

Description: Determination of the neutralizing antibody titer for a virus in virus neutralization reaction vs. baseline values and placebo

Measure: Neutralizing antibody levels

Time: at days 0, 14 and 28 from the start of vaccination compared to baseline values
16 A Phase 2 Randomized, Double-blind, Placebo-controlled, Proof of Concept Study to Evaluate the Efficacy and Safety of VIB4920 in Subjects With Sjögren's Syndrome (SS)

The purpose of the study is to evaluate the efficacy, safety, and tolerability of VIB4920 (formerly MEDI4920) in adult participants with Sjögren's Syndrome (SS).

NCT04129164
Conditions
  1. Sjögren's Syndrome
Interventions
  1. Drug: VIB4920
  2. Drug: Placebo
MeSH:Sjogren's Syndrome Syndrome

Primary Outcomes

Measure: Change From Baseline in European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) at Day 169 in Population 1

Time: Baseline (Day 1) and Day 169

Measure: Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at Day 169 in Population 2

Time: Baseline (Day 1) and Day 169

Secondary Outcomes

Measure: Change From Baseline in ESSPRI at Day 169 in Population 1

Time: Baseline (Day 1) and Day 169

Measure: Percentage of Participants achieving ESSDAI [3] and ESSDAI [4] response in Population 1

Time: Baseline (Day 1) to Day 169

Measure: Percentage of Participants achieving ESSPRI response in Population 2

Time: Baseline (Day 1) to Day 169

Measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Day 169 in Populations 1 and 2

Time: Baseline (Day 1) and Day 169

Measure: Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169 in Populations 1 and 2

Time: Baseline (Day 1) and Day 169

Measure: Patient's Global Impression of Severity at Day 169 in Populations 1 and 2

Time: Day 169

Measure: Number of participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Populations 1 and 2

Time: From Baseline (Day 1) up to Day 365

Measure: Number of participants With Adverse Events of Special Interest (AESIs) in Populations 1 and 2

Time: From Baseline (Day 1) up to Day 365

Measure: Number of Participants With Abnormal Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) Reported as TEAEs in Populations 1 and 2

Time: From Baseline (Day 1) up to Day 365

Measure: Plasma Concentration of VIB4920

Time: Day 1 to Day 365

Measure: Percentage of Participants With Positive Antibody Titer to VIB4920 in Populations 1 and 2

Time: Day 1 to Day 365
17 Double-blind, Placebo-controlled Study With an Open Dose Selection Period for Assessing the Safety and Immunogenicity of the Drug "BVRS-GamVac", a Vector Vaccine for the Prevention of the Middle East Respiratory Syndrome, Lyophilisate for the Preparation of a Solution for Intramuscular Administration, With the Participation of Healthy Volunteers

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreak. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~34.5%. The aim of the study is to assess the safety and immunogenicity of adenoviral-based vaccine against MERS - BVRS-GamVac.

NCT04130594
Conditions
  1. MERS (Middle East Respiratory Syndrome)
  2. MERS
Interventions
  1. Biological: BVRS-GamVac
  2. Other: placebo
MeSH:Coronavirus Infections Syndrome

Primary Outcomes

Description: Determination of Number of Participants With Adverse Events

Measure: Number of Participants With Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of Number of Participants With Serious Adverse Events

Measure: Number of Participants With Serious Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of Number of Participants with Solicited Local and Systemic Adverse Events

Measure: Number of Participants with Solicited Local and Systemic Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of antibody levels against the MERS-CoV glycoprotein S measured by an ELISA vs. baseline values (phase 1, phase 2) and placebo (phase 2)

Measure: Antibody levels against the MERS-CoV glycoprotein S measured by an enzyme-linked immunosorbent assay (ELISA)

Time: at days 0, 7, 14, 21, 28, 42, 56 and 90

Secondary Outcomes

Description: determination of specific T-cell- mediated response vs. baseline values (phase 1, phase 2) and placebo (phase 2)

Measure: Assessment of antigen-specific cell-mediated immune response

Time: at 0 and 14 days from the start of vaccination compared to baseline values (day 0)

Description: Determination of the neutralizing antibody titer for a virus in virus neutralization reaction vs. baseline values

Measure: Neutralizing antibody levels

Time: at days 0, 14 and 28
18 A Phase Ib Study to Determine the Safety and Immunogenicity of the Candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Vaccine ChAdOx1 MERS in Healthy Adult Middle Eastern Volunteers

A phase Ib study to determine the safety and immunogenicity of the candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) vaccine ChAdOx1 MERS in healthy adult Middle Eastern volunteers

NCT04170829
Conditions
  1. Middle East Respiratory Syndrome Coronavirus
Interventions
  1. Biological: ChAdOx1 MERS
MeSH:Coronavirus Infections Syndrome

Primary Outcomes

Description: The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. Change from baseline for safety laboratory measures will also be collected. Occurrence of serious adverse events will be collected during the whole study duration

Measure: Occurrence of solicited and unsolicited local and systemic adverse events

Time: 28 days following the vaccination

Secondary Outcomes

Description: ELISA to quantify antibodies to MERS Spike protein antigen Ex vivo ELISpot responses to MERS Spike protein antigen

Measure: Measures of immunogenicity to the ChAdOx1 MERS vaccine

Time: 6.5 months following completion of the vaccination regimen
19 Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs

The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.

NCT04278404
Conditions
  1. Coronavirus Infection (COVID-19)
  2. Pulmonary Arterial Hypertension
  3. Urinary Tract Infections in Children
  4. Hypertension
  5. Pain
  6. Hyperphosphatemia
  7. Primary Hyperaldosteronism
  8. Edema
  9. Hypokalemia
  10. Heart Failure
  11. Hemophilia
  12. Menorrhagia
  13. In
  14. Insomnia
  15. Pneumonia
  16. Skin Infection
  17. Arrythmia
  18. Asthma in Children
  19. Bronchopulmonary Dysplasia
  20. Adrenal Insufficiency
  21. Fibrinolysis; Hemorrhage
  22. Attention Deficit Hyperactivity Disorder
  23. Multisystem Inflammatory Syndrome in Children (MIS-C)
  24. Kawasaki Disease
  25. Coagulation Disorder
  26. Down Syndrome
Interventions
  1. Drug: The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care:
MeSH:Infection Communicable Diseases Urinary Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome Bronchopulmonary Dysplasia Down Syndrome Menorrhagia Hypertension Hemostatic Disorders Mucocutaneous Lymph Node Syndrome Blood Coagulation Disorders Hyperphosphatemia Hypokalemia Adrenal Insufficiency Hyperaldosteronism Disease Syndrome Hemorrhage Attention Deficit Disorder with Hyperactivity
HPO:Abnormality of coagulation Abnormality of the coagulation cascade Adrenal insufficiency Attention deficit hyperactivity disorder Hyperaldosteronism Hyperphosphatemia Hypertension Hypokalemia Menorrhagia Primary hyperaldosteronism

Primary Outcomes

Measure: Clearance (CL) or apparent oral clearance (CL/F) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

Measure: Volume of distribution (V) or apparent oral volume of distribution (V/F) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

Measure: Elimination rate constant (ke) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

Measure: Half-life (t1/2) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

Measure: Absorption rate constant (ka) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

Measure: AUC (area under the curve) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

Measure: Maximum concentration (Cmax) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

Measure: Time to achieve maximum concentration (Tmax) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.
20 Nitric Oxide Gas Inhalation Therapy for Severe Acute Respiratory Syndrome Due to COVID-19.

The investigators will enroll 102 patients with a confirmed diagnosis of COVID-19. Patients will be randomized to receive either inhaled nitric oxide (per protocol) or placebo. ICU Standards of care will be the institution's own protocols (such as ventilation strategies and use and dose of antivirals and antimicrobials, steroids, inotropic and vasopressor agents).

NCT04290871
Conditions
  1. Coronavirus
  2. SARS (Severe Acute Respiratory Syndrome)
Interventions
  1. Drug: Nitric Oxide Gas
MeSH:Coronavirus Infe Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: Percentage of patients that have a PaO2/FiO2 ratio steadily > 300 in ambient air

Measure: SARS-free patients at 14 days

Time: 14 days since beginning of treatment

Secondary Outcomes

Measure: Survival at 28 days

Time: 28 days

Measure: Survival at 90 days

Time: 90 days

Description: Composite outcome in which: Death=0, Days of treatment =1

Measure: SARS-free days at 28 days

Time: 28 days

Description: Composite outcome in which: Death=0, Days of treatment =1

Measure: SARS -free days at 90 days

Time: 90 days

Description: Incidence

Measure: Renal Replacement Therapy

Time: 28 days

Description: Incidence

Measure: Liver Failure

Time: 28 days

Description: Incidence of patients requiring VA-ECMO, LVAD, IABP

Measure: Mechanical Support of Circulation

Time: 28 days

Description: In ambient air if possible

Measure: PaO2/FiO2 ratio in ambient air

Time: daily for 28 days
21 Clinical Application of Stem Cell Educator Therapy for the Treatment of Viral Inflammation Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Currently, 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.

NCT04299152
Conditions
  1. Severe Acute Respiratory Syndrome (SARS) Pneumonia
Interventions
  1. Combination Product: Stem Cell Educator-Treated Mononuclear Cells Apheresis
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome Inflammation
HPO:Pneumonia

Primary Outcomes

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 weeks

Secondary Outcomes

Description: 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 weeks

Description: 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 weeks

Description: 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 weeks

Description: 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 weeks
22 Nitric Oxide Gas Inhalation Therapy for Mechanically Ventilated Patients With Severe Acute Respiratory Syndrome Caused by SARS-CoV2: a Randomized Clinical Trial.

Severe acute respiratory syndrome (SARS-CoV2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used in as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In-vitro and clinical evidence indicate that inhaled nitric oxide gas (iNO) has also antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. This is a multicenter single-blinded randomized controlled trial with 1:1 individual allocation

NCT04306393
Conditions
  1. SARS (Severe Acute Respiratory Syndrome)
  2. Coronavirus
Interventions
  1. Drug: Nitric Oxide Gas
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: Difference within groups in terms of PaO2/FiO2 ratio. If a patient dies during the first 48 hours of treatment, the last available blood gas analysis will be used.

Measure: Change of arterial oxygenation at 48 hours from enrollment

Time: 48 hours

Secondary Outcomes

Description: Time to recover gas exchange to a PaO2/FiO2 =/> 300 for at least 24 hours during the first 28 days after enrollment, within each group and comparison between groups. If the patient dies before day 28, the patient will be considered as "never recovered".

Measure: Time to reach normoxemia during the first 28 days after enrollment

Time: 28 days

Description: Daily proportion of patients with a PaO2/FiO2 ratio > 300 for at least 24 hours within each group and comparison between groups. If a patient dies before day 28, the patient will be considered as "never recovered".

Measure: Proportion of SARS-nCoV-2 free patients during the first 28 days after enrollment

Time: 28 days

Description: Proportion of patients surviving at 28 days within each group and comparison between groups.

Measure: Survival at 28 days from enrollment

Time: 28 days

Description: Proportion of patients surviving at 90 days within each group and comparison between groups.

Measure: Survival at 90 days from enrollment

Time: 90 days

Other Outcomes

Description: Expressed as PaO2/FiO2 ratio within each group and comparison between groups.

Measure: Daily oxygenation in the two groups until day 28

Time: 28 days

Description: Proportion of patients needing RRT within each group and comparison between groups.

Measure: Need for new renal replacement therapy during the first 28 days

Time: 28 days

Description: Proportion of patients needing (i.e., ECMO, intra-aortic balloon pump, VADs) within each group and comparison between groups.

Measure: Mechanical support of circulation during the first 28 days

Time: 28 days

Description: Average days without need for vasopressors within each group and comparison between groups.

Measure: Days free of vasopressors during the first 28 days

Time: 28 days

Description: Average days without need for mechanical ventilation within each group and comparison between groups.

Measure: Ventilator-free day at 28 days

Time: 28 days

Description: Time to obtain first negative upper respiratory trait sample in the 2019-nCoV rt-PCR assay. Average within groups and comparison between groups.

Measure: Time to SARS-CoV-2 rt-PCR negative in upper respiratory tract specimen

Time: 28 days

Description: Average days out of ICU within each group and comparison between groups.

Measure: ICU-free days at 28 days

Time: 28 days

Description: Average days of ICU admission within each group and comparison between groups.

Measure: ICU length of stay

Time: 90 days
23 A Retrospective Study of Evaluating Safety and Efficacy of Tocilizumab Compared to Continuous Renal Replacement Therapy in Controlling CRS Triggered by COVID-19

Some patients infected with the COVID-19 can develop uncontrolled immune response, leading to potentially life-threatening damage to lung tissue. Tocilizumab was first approved by the U.S. FDA in 2010 for rheumatoid arthritis and might now be used to treat serious COVID-19 patients with lung damage, according to China's National Health Commission updated its treatment guidelines in 7th version.Continuous Renal Replacement Therapy (CRRT) was recommended by China's National Health Commission treatment guidelines in 1st-7th version to control sever COVID-19 patients.

NCT04306705
Conditions
  1. Covid-19
  2. SARS
  3. Cytokine Storm
  4. Cytokine Release Syndrome
  5. Tocilizumab
Interventions
  1. Drug: Tocilizumab
  2. Other: Standard of care
  3. Procedure: Continuous renal replacement therapy
MeSH:Syndrome

Primary Outcomes

Description: This is a composite outcome measure. Criteria for fever normalization: Temperature < 36.6 °C armpit, < 37.2 °C oral sustained for at least 72 hours and criteria for oxygen normalization: peripheral capillary oxygen saturation (Sp02) > 94% sustained for at least 72 hours.

Measure: Proportion of Participants With Normalization of Fever and Oxygen Saturation Through Day 14

Time: First dose date up to 14 days

Secondary Outcomes

Description: Measured in days

Measure: Duration of hospitalization

Time: Up to 28 days

Description: Criteria for: Temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for at least 72 hours.

Measure: Proportion of Participants With Normalization of Fever Through Day 14

Time: First dose date up to 14 days

Description: Blood routine test

Measure: Change from baseline in white blood cell and differential count

Time: Day 1 through Day 28

Description: Oropharyngeal or anal swabs

Measure: Time to first negative in 2019 novel Corona virus RT-PCR test

Time: Up to 28 days

Description: Date and cause of death (if applicable).

Measure: All-cause mortality

Time: up to 12 weeks

Description: Serum hsCRP

Measure: Change from baseline in hsCRP

Time: Day 1 through Day 28

Description: Serum inflammatory cytokines

Measure: Change from baseline in cytokines IL-1β, IL-10, sIL-2R, IL-6, IL-8 and TNF-α

Time: Day 1 through Day 28

Description: Flow cytometry for peripheral whole blood

Measure: Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells

Time: Day 1 through Day 28 (if applicable)
24 Uppsala Intensive Care Study of Mechanisms for Organ Dysfunction in Covid-19

The study aims to investigate organ dysfunction and biomarkers in patients with suspected or verified COVID-19 during intensive care at Uppsala University Hospital.

NCT04316884
Conditions
  1. COVID-19
  2. Organ Dysfunction Syndrome Sepsis
  3. Organ Dysfunction Syndrome, Multiple
  4. Septic Shock
  5. Acute Kidney Injury
  6. Acute Respiratory Distress Syndrome
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Acute Kidney Injury Syndrome Systemic Inflammatory Response Syndrome Multiple Organ Failure
HPO:Acute kidney injury

Primary Outcomes

Description: KDIGO AKI score

Measure: Acute Kidney Injury

Time: During Intensive Care, an estimated average of 10 days.

Secondary Outcomes

Description: Acute Respiratory Distress Syndrome yes/no

Measure: ARDS

Time: During intensive care, an estimated average of 10 days.

Description: Death within 30 days of ICU admission

Measure: 30 day mortality

Time: 30 days

Description: Death within 1 year of ICU admission

Measure: 1 year mortality

Time: 1 year

Description: Development of Chronic Kidney Disease

Measure: Chronic Kidney Disease

Time: 60 days and 1 year after ICU admission

Description: Sequential Organ Failure Score as a continuous variable

Measure: SOFA-score

Time: During Intensive Care, an estimated average of 10 days.
25 Efficacy and Safety of Chloroquine Diphosphate for the Treatment of Hospitalized Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV2: a Phase IIb, Double-blind, Randomized Adaptive Clinical Trial

In 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.

NCT04323527
Conditions
  1. SARS-CoV Infection
  2. Severe Acute Respiratory Syndrome (SARS) Pneumonia
Interventions
  1. Drug: Chloroquine diphosphate
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
HPO:Pneumonia

Primary Outcomes

Description: proportion of deaths at day 28 between groups compared

Measure: Mortality rate reduction of 50% by day 28

Time: 28 days after randomization

Secondary Outcomes

Description: 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 dose

Description: 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 dose

Description: clinical status

Measure: Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization

Time: during and after intervention, up to 28 days

Description: supplemental oxygen

Measure: Duration of supplemental oxygen (if applicable)

Time: during and after intervention, up to 28 days

Description: mechanical ventilation

Measure: Duration of mechanical ventilation (if applicable)

Time: during and after intervention, up to 28 days

Description: hospitalization

Measure: Absolute duration of hospital stay in days

Time: during and after intervention, up to 28 days

Description: adverse events grade 3 and 4

Measure: Prevalence of grade 3 and 4 adverse events

Time: during and after intervention, up to 28 days

Description: adverse events

Measure: Prevalence of serious adverse events

Time: during and after intervention, up to 28 days

Description: increase or decrease in serum creatinine compared to baseline

Measure: Change in serum creatinine level

Time: during and after intervention, up to 28 days

Description: 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 days

Description: 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 days

Description: 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 days

Description: virus clearance from respiratory tract secretion

Measure: Change in detectable viral load in respiratory tract swabs

Time: during and after intervention, up to 28 days

Description: viremia in blood detected through RT-PCR

Measure: Viral concentration in blood samples

Time: during and after intervention, up to 28 days

Description: death

Measure: Absolute number of causes leading to participant death (if applicable)

Time: during and after intervention, up to 28 days
26 Prolonged Low Doses of Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

COVID-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).

NCT04323592
Conditions
  1. Severe Acute Respiratory Syndrome (SARS) Pneumonia
  2. Coronavirus Infections
  3. ARDS, Human
Interventions
  1. Drug: Methylprednisolone
  2. Other: standard care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Distress Syndrome, Adult Syndrome
HPO:Pneumonia

Primary Outcomes

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 days

Description: 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 days

Description: We reported below the number of participants admitted to ICU within 28 days.

Measure: Admission to Intensive Care Unit (ICU)

Time: 28 days

Description: We reported below the number of participants who needed endotracheal intubation during ICU admission

Measure: Endotracheal Intubation (Invasive Mechanical Ventilation)

Time: 28 days

Secondary Outcomes

Description: 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 days

Description: number of days free from mechanical ventilation (both invasive and non-invasive) by day 28

Measure: Number of Days Free From Mechanical Ventilation

Time: 28 days
27 Integrated Distance Management Strategy for Patients With Cardiovascular Disease (Ischaemic Coronary Artery Disease, High Blood Pressure, Heart Failure) in the Context of the COVID-19 Pandemic

Management of known patients with cardiovascular disease (in particular the whole spectrum of atherosclerotic ischaemic coronary artery disease, essential hypertension under treatment, and also patients with chronic heart failure under medication) and with other associated chronic pathologies, with obvious effects on the management of the pandemic with modern / distance means (e-Health) of patients at high risk of mortality in contact with coronavirus. Given the Covid-19 Pandemic, all the above complex cardiovascular patients are under the obligation to stay in the house isolated and can no longer come to standard clinical and paraclinical monitoring and control visits. Therefore, a remote management solution (tele-medicine) of these patients must be found. The Investigators endeavour is to create an electronic platform to communicate with these patients and offer solutions for their cardiovascular health issues (including psychological and religious problems due to isolation). The Investigators intend to create this platform for communicating with a patient and stratify their complaints in risk levels. A given specialist will sort and classify their needs on a scale, based on specific algorithms (derived from the clinical European Cardiovascular Guidelines), and generate specific protocols varying from 911 like emergencies to cardiological advices or psychological sessions. These could include medication changing of doses, dietary advices or exercise restrictions. Moreover, in those patients suspected of COVID infection, special assistance should be provided per protocol.

NCT04325867
Conditions
  1. Angina Pectoris
  2. Acute Coronary Syndrome
  3. Coronary Syndrome
  4. Coronary Artery Disease
  5. Angioplasty
  6. Stent Restenosis
  7. Hypertension
  8. Heart Failure, Systolic
  9. Depression, Anxiety
  10. Covid-19
  11. Isolation, Social
Interventions
  1. Other: Tele-medicine platform
MeSH:Heart Failure Cardiovascular Diseases Coronary Artery Disease Myocardial Ischemia Coronary Disease Acute Coronary Syndrome Angina Pectoris Heart Failure, Systolic Syndrome
HPO:Abnormality of the cardiovascular system Angina pectoris Congestive heart failure Coronary artery atherosclerosis Left ventricular dysfunction Myocardial infarction Right ventricular failure

Primary Outcomes

Description: Development of an electronic (e-HEALTH) framework structure for management of patients with known cardiovascular disease in COVID19 pandemic social context

Measure: Providing a special electronic platform (e-health) for remote managing cardiovascular outpatients

Time: 6 months

Description: patients come into direct contact with the case coordinator, who provides ongoing assistance, including for connecting to devices that ensure real-time data transmission and directing to specialist teams that establish stage diagnosis and management / therapy behavior (including adjustment). doses, decisions to discontinue medication or to add medication);

Measure: Number of patients included in this platform

Time: 6 months

Secondary Outcomes

Description: Will be the number of sessions per patient multiplied with the number of patients included

Measure: Number of consultations/sessions given

Time: 6 months
28 Efficacy of Hydroxychloroquine for Post-exposure Prophylaxis (PEP) to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Adults Exposed to Coronavirus Disease (COVID-19): a Blinded, Randomized Study

This is a clinical study for the prevention of SARS-CoV-2 infection in adults exposed to the virus. This study will enroll up to 2000 asymptomatic men and women 18 to 80 years of age (inclusive) who are close contacts of persons with laboratory confirmed SARS-CoV-2 or clinically suspected COVID-19. Eligible participants will be enrolled and randomized to receive the intervention or placebo at the level of the household (all eligible participants in one household will receive the same intervention).

NCT04328961
Conditions
  1. COVID-19
  2. Corona Virus Infection
  3. SARS (Severe Acute Respiratory Syndrome)
  4. SARS-CoV-2
Interventions
  1. Drug: Hydroxychloroquine Sulfate
  2. Drug: Ascorbic Acid
MeSH:Infection Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

Primary Outcomes

Description: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected daily for 14 days

Measure: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection

Time: Day 1 through Day 14 after enrolment

Description: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected at study exit

Measure: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection

Time: Day 28 after enrolment

Secondary Outcomes

Description: Safety and tolerability of Hydroxychloroquine as SARS-CoV-2 PEP in adults

Measure: Rate of participant-reported adverse events

Time: 28 days from start of Hydroxychloroquine therapy

Description: PCR-confirmed COVID-19 diagnosis

Measure: Incidence rates of COVID-19 through study completion

Time: 28 days from enrolment
29 Safety and Efficacy Study of Human Embryonic Stem Cells Derived M Cells (CAStem) for the Treatment of Severe COVID-19 Associated With or Without Acute Respiratory Distress Syndrome (ARDS)

A 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.

NCT04331613
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Virus; Pneumonia
  4. Acute Lung Injury
Interventions
  1. Biological: CAStem
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

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 treatment

Description: Evaluation by chest CT

Measure: Changes of lung imaging examinations

Time: Within 28 days after treatment

Secondary Outcomes

Description: Marker for SARS-CoV-2

Measure: Time to SARS-CoV-2 RT-PCR negative

Time: Within 28 days after treatment

Description: The duration of a fever above 37.3 degrees Celsius

Measure: Duration of fever (Celsius)

Time: Within 28 days after treatment

Description: Marker for efficacy

Measure: Changes of blood oxygen (%)

Time: Within 28 days after treatment

Description: Marker for efficacy

Measure: Rate of all-cause mortality within 28 days

Time: Within 28 days after treatment

Description: Counts of lymphocyte in a litre (L) of blood

Measure: Lymphocyte count (*10^9/L)

Time: Within 28 days after treatment

Description: Alanine aminotransferase in unit (U)/litre(L)

Measure: Alanine aminotransferase (U/L)

Time: Within 28 days after treatment

Description: Creatinine in micromole (umol)/litre(L)

Measure: Creatinine (umol/L)

Time: Within 28 days after treatment

Description: Creatine kinase in U/L

Measure: Creatine kinase (U/L)

Time: Within 28 days after treatment

Description: C-reactive in microgram (mg)/litre(L)

Measure: C-reactive protein (mg/L)

Time: Within 28 days after treatment

Description: Procalcitonin in nanogram (ng)/litre(L)

Measure: Procalcitonin (ng/L)

Time: Within 28 days after treatment

Description: Lactate in millimole(mmol)/litre(L)

Measure: Lactate (mmol/L)

Time: Within 28 days after treatment

Description: IL-1beta in picogram(pg)/millilitre(mL)

Measure: IL-1beta (pg/mL)

Time: Within 28 days after treatment

Description: IL-2 in pg/mL

Measure: IL-2 (pg/mL)

Time: Within 28 days after treatment

Description: IL-6 in pg/mL

Measure: IL-6 (pg/mL)

Time: Within 28 days after treatment

Description: IL-8 in pg/mL

Measure: IL-8 (pg/mL)

Time: Within 28 days after treatment
30 Cell Therapy Using Umbilical Cord-derived Mesenchymal Stromal Cells in SARS-CoV-2-related ARDS

Whereas the pandemic due do Covid-19 continues to spread, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Severe Acute Respiratory Distress Syndrome in 30% of patients with a 30%-60% mortality rate for those requiring hospitalization in an intensive care unit. The main physio-pathological hallmark is an acute pulmonary inflammation. Currently, there is no treatment. Mesenchymal stem cells (MSC) feature several attractive characteristics: ease of procurement, high proliferation potential, capacity to home to inflammatory sites, anti-inflammatory, anti-fibrotic and immunomodulatory properties. If all MSC share several characteristics regardless of the tissue source, the highest productions of bioactive molecules and the strongest immunomodulatory properties are yielded by those from the Wharton's jelly of the umbilical cord. An additional advantage is that they can be scaled-up to generate banks of cryofrozen and thus readily available products. These cells have already been tested in several clinical trials with an excellent safety record. The objective of this project is to treat intubated-ventilated patients presenting with a SARS-CoV2-related Acute Respiratory Distress Syndrome (ARDS) of less than 96 hours by three intravenous infusions of umbilical cord Wharton's jelly-derived mesenchymal stromal cells (UC-MSC) one every other day (duration of the treatment: one week). The primary endpoint is the PaO2/FiO2 ratio at day 7. The evolution of several inflammatory markers, T regulatory lymphocytes and donor-specific antibodies will also be monitored. The trial will include 40 patients, of whom 20 will be cell-treated while the remaining 20 patients will be injected with a placebo solution in addition to the standard of care. Given the pathophysiology of SARS-CoV2, it is thus sound to hypothesize that the intravenous administration of UC-MSC during the initial phase of ARDS could control inflammation, accelerate its recovery with improved oxygenation, reduced mechanical ventilation and ventilation weaning time and therefore reduced length of stay in intensive care. The feasibility of the project is supported by the expertise of the Meary Cell and Gene Therapy Center, which is approved for the production of Advanced Therapy Medicinal Products and has already successfully prepared the first batches of cells, as well as by the involvement of a cardiac surgery team which will leverage its experience with stem cells for the treatment of heart failure to make it relevant to the Stroma-Cov-2 project.

NCT04333368
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
  2. Severe Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Umbilical cord Wharton's jelly-derived human
  2. Other: NaCl 0.9%
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: Respiratory efficacy evaluated by the increase in PaO2/FiO2 ratio from baseline to day 7 in the experimental group compared with the placebo group

Time: From baseline to day 7

Secondary Outcomes

Measure: Lung injury score

Time: From baseline to day 28

Measure: Oxygenation index

Time: From baseline to day 28

Measure: In-hospital mortality

Time: From baseline to day 28

Measure: Mortality

Time: At day 28

Measure: Ventilator-free days

Time: From baseline to day 28

Measure: Number of days between randomization and the first day the patient meets weaning criteria o Number of days between randomization and the first day the patient meets PaO2/FiO2 > 200 (out of a prone positioning session)

Time: From baseline to day 28

Measure: Cumulative use of sedatives

Time: From baseline to day 28

Measure: Cumulative duration of use of sedatives

Time: From baseline to day 28

Measure: Cumulative duration of use of neuromuscular blocking agents (other than used for intubation)

Time: From baseline to day 28

Measure: Cumulative use of neuromuscular blocking agents (other than used for intubation)

Time: From baseline to day 28

Measure: ICU-acquired weakness and delirium

Time: From baseline to day 28

Measure: Treatment-induced toxicity rate and adverse events up to day 28

Time: From baseline to day 28

Measure: Quality of life at one year (EQ5D-3L quality of life questionnaire)

Time: At 6 months and 12 months

Measure: Measurements of plasmatic cytokines (IL1, IL6, IL8, TNF-alpha, IL10, TGF-beta, sRAGE, Ang2) level

Time: At day 1, 3, 5, 7 and 14

Measure: Anti-HLA antibodies plasmatic dosage

Time: From baseline to day 14, and at 6 months
31 Treatment of Severe Acute Respiratory Syndrome Caused by COVID-19 With Ruxolitinib

In December 2019, a new virus emerged in Wuhan, China rapidly becoming a pandemic with registered cases above 800,000 around the world. The virus is now known as SARS-CoV2 calling its disease coronavirus-19 or COVID-19. The mortality of the virus has been reported around 2-10% and its causes because of the proinflammatory immune response generated on the host. The cytokines involved in the immune response to COVID-19 are IL-1, IL-2, IL4, IL-6, IL-10, IL-12, IL-13, IL-17, GCSF, MCSF, IP-10, MCP-1, MIP-1α, HGF, IFN-γ y TNF-α. Ruxolitinib is an inhibitor of JAK 1/2 which is responsable for multiple cellular signals including the proinflammatory IL-6. Ruxolitinib works as and immunomodulator decreasing the cytotoxic T lymphocytes and increasing the Treg cells. This study is intended to stop the disregulated immune response caused by COVID-19 that generates the pneumonia and subsequent severe acute respiratory syndrome.

NCT04334044
Conditions
  1. COVID-19
  2. Severe Acute Respiratory Syndrome Coronavirus 2
Interventions
  1. Drug: Ruxolitinib Oral Tablet
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: Presence of recovery of pneumonia characterized by cease of respiratory symptoms

Measure: Recovery of Pneumonia

Time: 14 days

Secondary Outcomes

Description: Increment or decrease in mg/ml of C-reactive protein

Measure: Response of C-reactive protein

Time: 14 days

Description: Increment or decrease in ng/ml of ferritin

Measure: Response of Ferritin

Time: 14 days

Description: Increment or decrease in mg/ml of D-dimer

Measure: Response of D-dimer

Time: 14 days

Description: Requirement of Intensive Care Unit on the patients under treatment

Measure: Rate of ICU admission

Time: 14 days

Description: Requirement of mechanical ventilation on the patients under treatment

Measure: Rate of mechanical ventilation

Time: 14 days

Description: Time since the diagnosis to the last follow up (recovery or death)

Measure: Overall Survival

Time: 1 month

Description: Rate of adverse events associated with ruxolitinib

Measure: Toxicity Rate

Time: 1 month
32 PRAETORIAN-COVID: A Double-blind, Placebo-controlled Randomized Clinical Trial With Valsartan for PRevention of Acute rEspiraTORy dIstress Syndrome in hospitAlized patieNts With SARS-COV-2 (COVID-19) Infection Disease

Rationale: The current SARS-CoV-2 pandemic has a high burden of morbidity and mortality due to development of the so-called acute respiratory distress syndrome (ARDS). The renin-angiotensin-system (RAS) plays an important role in the development of ARDS. ACE2 is one of the enzymes involved in the RAS cascade. Virus spike protein binds to ACE2 to form a complex suitable for cellular internalization. The downregulation of ACE2 results in the excessive accumulation of angiotensin II, and it has been demonstrated that the stimulation of the angiotensin II type 1a receptor (AT1R) increases pulmonary vascular permeability, explaining the increased lung pathology when activity of ACE2 is decreased. Currently available AT1R blockers (ARBs) such as valsartan, have the potential to block this pathological process mediated by angiotensin II. There are presently two complementary mechanisms suggested: 1) ARBs block the excessive angiotensin-mediated AT1R activation, and 2) they upregulate ACE2, which reduces angiotensin II concentrations and increases the production of the protective vasodilator angiotensin 1-7. In light of the above, ARBs may prevent the development of ARDS and avert morbidity (admission to intensive care unit (ICU) and mechanical ventilation) and mortality. Objective: To investigate the effect of the ARB valsartan in comparison to placebo on the occurrence of one of the following items, within 14 days of randomization:1) ICU admission; 2) Mechanical ventilation; 3) Death. Study design: A double-blind, placebo-controlled 1:1 randomized clinical trial Study population: Adult hospitalized SARS-CoV-2-infected patients (n=651). Intervention: The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160mg b.i.d. and the placebo arm will receive a matching placebo also titrated to blood pressure. Treatment duration will be 14 days or up to hospital discharge < 14 days or occurrence of the primary endpoint if < 14 days. Main study endpoint: The primary study endpoint is the occurrence within 14 days of randomization of either: 1) ICU admission; 2) Mechanical ventilation; 3) Death.

NCT04335786
Conditions
  1. Acute Respiratory Distress Syndrome
  2. SARS-CoV-2
  3. COVID
  4. COVID-19
  5. Severe Acute Respiratory Syndrome
Interventions
  1. Drug: Valsartan (Diovan)
  2. Drug: Placebo oral tablet
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Death is defined as all-cause mortality

Measure: first occurrence of intensive care unit admission, mechanical ventilation or death

Time: within 14 days

Secondary Outcomes

Description: All-cause mortality; and time to all-cause mortality

Measure: Death

Time: Within 14 days, 30 days, 90 days and at 1 year

Description: Occurrence of mechanical ventilation and time to ventilation

Measure: Mechanical ventilation

Time: within 14 days

Description: Occurrence of ICU admission and time to admission

Measure: Intensive care unit admission

Time: within 14 days

Description: Defined as a 50% decline in estimated glomerular filtration rate relative to baseline, or decrease of >30 ml/min/1.73m2 and to a value below 60 ml/min/1.73m2

Measure: Occurrence of acute kidney injury

Time: Within 14 days
33 Phase IIb Study to Evaluate the Efficacy and Safety of Chloroquine Diphosphate in the Treatment of Patients With Comorbidities, Without Severe Acute Respiratory Syndrome, Under the New Coronavirus (SARS-CoV2): a Double-blind, Randomized, Placebo-controlled Clinical Trial

This 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).

NCT04342650
Conditions
  1. COVID-19
  2. SARS-CoV Infection
  3. Severe Acute Respiratory Syndrome (SARS) Pneumonia
  4. Clinical Trial
Interventions
  1. Drug: Chloroquine Diphosphate
  2. Drug: Placebo oral tablet
MeSH:Infection Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
HPO:Pneumonia

Primary Outcomes

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 randomization

Secondary Outcomes

Description: Mortality rate between intervention and placebo group on days 7, 14, and 28 after randomization

Measure: Mortality rate

Time: after randomization, up to 28 days

Description: 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 days

Description: Viral load change in blood and oropharyngeal swab samples

Measure: Viral concentration

Time: After randomization, up to 7 days

Description: Incidence of serious adverse events during and after treatment

Measure: Cumulative incidence of serious adverse events

Time: During and after intervention, up to 28 days

Description: 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 days

Description: proportion of discontinuation or temporary suspension of treatment (for any reason)

Measure: Proportion of patients with discontinued treatment

Time: after randomization, up to 28 days

Description: proportion of patients with increased levels of troponin I

Measure: Incidence of cardiac lesions

Time: after randomization, up to 120 days

Description: proportion and magnitude of QTcF interval increases higher than 500ms

Measure: Incidence of cardiac disfunctions

Time: after randomization, up to 120 days

Description: Changes measured on day 120 will be compared to baseline, through spirometry.

Measure: Change in respiratory capacity

Time: Day 120 after randomization
34 Efficacy of Injectable Methylprednisolone Sodium Succinate in the Treatment of Patients With Signs of Severe Acute Respiratory Syndrome Under the New Coronavirus (SARS-CoV2): a Phase IIb, Randomized, Double-blind, Placebo-controlled, Clinical Trial.

This is a double-blind, randomized, placebo-controlled, phase IIb clinical trial to assess the efficacy of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 416 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 MP (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).

NCT04343729
Conditions
  1. SARS-CoV Infection
  2. Severe Acute Respiratory Syndrome (SARS) Pneumonia
Interventions
  1. Drug: Methylprednisolone Sodium Succinate
  2. Drug: Placebo solution
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
HPO:Pneumonia

Primary Outcomes

Description: Mortality rate on day 28, after randomization

Measure: Mortality rate at day 28

Time: on day 28, after randomization

Secondary Outcomes

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.
35 Dexamethasone Combined With Hydroxychloroquine Compared to Hydroxychloroquine Alone for Treatment of Severe Acute Respiratory Distress Syndrome Induced by Coronavirus Disease 19 (COVID-19): a Multicentre, Randomised Controlled Trial

Single blind randomized clinical trial designed to evaluate the efficacy of the combination of hydroxychloroquine and dexamethasone as treatment for severe Acute Respiratory Distress Syndrome (ARDS) related to coronavirus disease 19 (COVID-19). We hypothesize that dexamethasone (20 mg for 5 days followed by 10 mg for 5 days) combined with 600 mg per day dose of hydroxychloroquine for 10 days will reduce the 28-day mortality compared to hydroxychloroquine alone in patients with severe ARDS related COVID-19.

NCT04347980
Conditions
  1. Respiratory Distress Syndrome, Adult
  2. COVID-19
Interventions
  1. Drug: Dexamethasone and Hydroxychloroquine
  2. Drug: Hydroxychloroquine
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Mortality rate evaluated 28 days after randomization

Measure: Day-28 mortality

Time: 28 days after randomization

Secondary Outcomes

Description: Ventilator-free days (VFDs) at 28 days are one of several organ failure-free outcome measures to quantify the efficacy of therapies and interventions. VFDs are typically defined as follows: VFDs = 0 if subject dies within 28 days of mechanical ventilation. VFDs = 28 - x if successfully liberated from ventilation x days after initiation. VFDs = 0 if the subject is mechanically ventilated for >28 days.

Measure: Ventilator-free days

Time: 28 days after randomization

Description: Mortality rate evaluated during Intensive care unit stay

Measure: Intensive Care Unit mortality

Time: Up to 60 days after randomization

Description: Mortality rate evaluated 60 days after randomization

Measure: Day-60 mortality

Time: 60 days after randomization

Description: Number of patients with pneumonia diagnosed during intensive care unit stay

Measure: Nosocomial pneumonia

Time: Up to 60 days after randomization

Description: Number of patients with bacteremia diagnosed during intensive care unit

Measure: Bacteremia

Time: Up to 60 days after randomization

Other Outcomes

Description: Placement of ECMO during intensive care unit stay

Measure: Extra corporeal membrane oxygenation (ECMO)

Time: Up to 60days after randomization

Description: Number of patients who underwent tracheostomy during intensive care unit stay

Measure: Tracheostomy

Time: Up to 60 days after randomization

Description: Number of Prone position session

Measure: Prone Position

Time: Up to 60 days after randomization
36 Value of Early Treatment With Polyvalent Immunoglobulin in the Management of Acute Respiratory Distress Syndrome Associated With SARS-CoV-2 Infections

As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.

NCT04350580
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Drug: Human immunoglobulin
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Sum of the days the patient did not receive VM, but if death occurs before D28, the score is zero

Measure: Ventilator-free days

Time: 28 days

Secondary Outcomes

Description: Vital status at 28 and 90 days

Measure: Mortality

Time: 28 and 90 days

Description: Used to determine the extent of a person's organ function or rate of failure, from 0 to 24, with severity increasing the higher the score

Measure: Sequential Organ Failure Assessment Score

Time: Days 1, 3, 7, 14, 21 and 28

Description: Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage)

Measure: P/F ratio

Time: Days 1, 3, 7, 14, 21 and 28

Description: Measure of lung compliance

Measure: Lung compliance

Time: Days 1, 3, 7, 14, 21 and 28

Description: Severity scoring of lung oedema on the chest radiograph

Measure: Radiological score

Time: Days 1, 3, 7, 14, 21 and 28

Description: Concentration in mg/L

Measure: Biological efficacy endpoints - C-reactive protein

Time: Days 1, 3, 7, 14, 21 and 28

Description: Concentration in microgram/L

Measure: Biological efficacy endpoints - Procalcitonin

Time: Days 1, 3, 7, 14, 21 and 28

Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes

Measure: Immunological profile

Time: Up to 28 days

Description: Use of corticosteroids, antiretroviral, chloroquine

Measure: Number of patients using other treatments for COVID-19 related ARDS

Time: Up to 28 days

Description: Diagnosis of deep vein thrombosis or pulmonary embolism through imaging exam (eg ultrasound and CT scan)

Measure: Occurrence of deep vein thrombosis or pulmonary embolism

Time: 28 days

Description: Total time of mechanical ventilation, weaning and use of neuromuscular blockade

Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation

Time: 28 days

Description: Divided in 3 stages, with higher severity of kidney injury in higher stages

Measure: Kidney Disease: Improving Global Outcomes (KDIGO) score and need for dialysis

Time: 28 days

Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

Measure: Occurrence of adverse event related to immunoglobulins

Time: 28 days

Description: Medical research council sum score on awakening

Measure: Occurrence of critical illness neuromyopathy

Time: Up to 28 days

Description: Radiological and clinical context associated with a bacteriological sampling in culture of tracheal secretions, bronchiolar-alveolar lavage or a protected distal sampling

Measure: Occurrence of ventilator-acquired pneumonia

Time: Up to 28 days
37 Evaluation of Respiratory Mechanics and Lung Recruitment in Patients With SARS-CoV-2 Associated Acute Respiratory Distress Syndrome

The aim of this observationnal study is to describe respiratory mechanics and lung recruitement in patients with SARS-CoV-2 Associated Acute Respiratory Distress Syndrome who underwent invasive ventilation on endotracheal tube, admitted to the medical ICU of Angers university hospital . Statics measurements of respiratory system compliance were performed at 2 differents levels of PEEP (15 cmH2O and 5 cmH2O). The recruited volume is computed as the difference between the volume expired from PEEP 15 to 5 cmH2O and the volume predicted by compliance at PEEP 5 cmH2O . The recruitment-to-Inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and CRS at PEEP 5 cmH2O) is used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruiter patients.

NCT04350710
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID
Interventions
  1. Other: PEEP trial
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: no unit

Measure: Recruitment-to Inflation ratio (R/I ratio)

Time: Day 1

Description: no unit

Measure: Recruitment-to Inflation ratio (R/I ratio)

Time: Day 5

Description: no unit

Measure: Recruitment-to Inflation ratio (R/I ratio)

Time: Day 10

Secondary Outcomes

Description: Arterial blood gases

Measure: PaO2/FiO2 (mmHg)

Time: Day 1

Description: Arterial blood gases

Measure: PaO2/FiO2 (mmHg)

Time: Day 5

Description: Arterial blood gases

Measure: PaO2/FiO2 (mmHg)

Time: Day 10

Description: mL

Measure: Lung volume recruited (VRec)

Time: Day 1

Description: mL

Measure: Lung volume recruited (VRec)

Time: Day 5

Description: mL

Measure: Lung volume recruited (VRec)

Time: Day 10

Description: Obtained by inspiratory pause of 5 seconds

Measure: Plateau pressure (cm H2O)

Time: Day 1

Description: Obtained by inspiratory pause of 5 seconds

Measure: Plateau pressure (cm H2O)

Time: Day 5

Description: Obtained by inspiratory pause of 5 seconds

Measure: Plateau pressure (cm H2O)

Time: Day 10

Measure: Oesophagal pressure (cm H2O)

Time: Day 1

Measure: Oesophagal pressure (cm H2O)

Time: Day 5

Measure: Oesophagal pressure (cm H2O)

Time: Day 10

Measure: weight (Kg)

Time: Day 1

Measure: weight (Kg)

Time: Day 5

Measure: weight (Kg)

Time: Day 10

Measure: urine output (mL)

Time: day 1

Measure: urine output (mL)

Time: day 5

Measure: urine output (mL)

Time: day 10

Measure: serum creatinine (Umo/L)

Time: day 1

Measure: serum creatinine (Umo/L)

Time: day 5

Measure: serum creatinine (Umo/L)

Time: day 10

Measure: Mean arterial pressure (mmHg)

Time: day 1

Measure: Mean arterial pressure (mmHg)

Time: day 5

Measure: Mean arterial pressure (mmHg)

Time: day 10

Measure: Peak Pressure (cm H2O)

Time: Day 1

Measure: Peak Pressure (cm H2O)

Time: Day 5

Measure: Peak Pressure (cm H2O)

Time: Day 10

Description: Obtained by expiratory pause of 5 seconds

Measure: PEEP total (cm H2O)

Time: Day 1

Description: Obtained by expiratory pause of 5 seconds

Measure: PEEP total (cm H2O)

Time: Day 5

Description: Obtained by expiratory pause of 5 seconds

Measure: PEEP total (cm H2O)

Time: Day 10

Measure: PEP Set (cm H2O)

Time: Day 1

Measure: PEP Set (cm H2O)

Time: Day 5

Measure: PEP Set (cm H2O)

Time: Day 10

Measure: Height (cm)

Time: Day 1

Measure: Airway pening pressure (cm H2O)

Time: day 1

Measure: Airway pening pressure (cm H2O)

Time: day 5

Measure: Airway pening pressure (cm H2O)

Time: day 10

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 15 cmH2O (mL)

Time: Day 1

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 15 cmH2O (mL)

Time: Day 5

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 15 cmH2O (mL)

Time: Day 10

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 5 cmH2O (mL)

Time: Day 1

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 5 cmH2O (mL)

Time: Day 5

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 5 cmH2O (mL)

Time: Day 10
38 Efficacy and Safety of Aerosolized Intra-tracheal Dornase Alfa Administration in Patients With COVID19-induced Acute Respiratory Distress Syndrome (ARDS)

This study plans to learn more about the effects of Dornase Alfa in COVID19 (coronavirus disease of 2019) patients, the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Dornase Alfa is a FDA-approved drug for the treatment of cystic fibrosis, which facilitates mucus clearance by cutting apart neutrophil-derived extracellular double-stranded DNA. This study intends to define the impact of aerosolized intra-tracheal Dornase Alfa administration on the severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients. This drug might make lung mucus thinner and looser, promoting improved clearance of secretions and reduce extracellular double-stranded DNA-induced hyperinflammation in alveoli, preventing further damage to the lungs. The study will recruit mechanically ventilated patients hospitalized in ICU who have been diagnosed with COVID-19 and meet ARDS criteria. It is a prospective, randomized, controlled, multicentric, open-label clinical trial. The goal is to recruit 100 patients.

NCT04355364
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Dornase Alfa Inhalation Solution [Pulmozyme]
  2. Procedure: standard procedure
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: The primary endpoint is the occurrence of at least one grade improvement between D0 (inclusion) and D7 in the ARDS scale severity (Berlin criteria). For instance from severe to moderate or from moderate to mild

Measure: Efficacy of intratracheal administration: occurrence of at least one grade improvement

Time: Day 7
39 SOLIRIS® (Eculizumab) for the Treatment of Participants With Coronavirus Disease 2019 (COVID 19) - An Expanded Access Program for Hospital-based Emergency Treatment

This protocol provides access to eculizumab treatment for participants with severe COVID-19.

NCT04355494
Conditions
  1. COVID-19
  2. Pneumonia, Viral
  3. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Interventions
  1. Biological: eculizumab
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia

40 Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)

The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).

NCT04355728
Conditions
  1. Corona Virus Infection
  2. ARDS
  3. ARDS, Human
  4. Acute Respiratory Distress Syndrome
  5. COVID-19
Interventions
  1. Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.
  2. Other: Vehicle + Heparin along with best supportive care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Safety will be defined by the incidence of pre-specified infusion associated adverse events as assessed by treating physician

Measure: Incidence of pre-specified infusion associated adverse events

Time: Day 5

Description: Safety will be defined by the incidence of severe adverse events as assessed by treating physician

Measure: Incidence of Severe Adverse Events

Time: 90 days

Secondary Outcomes

Description: Number of participants that are alive at 90 days post first infusion follow up.

Measure: Survival rate after 90 days post first infusion

Time: 90 days

Description: Number of days participants were off ventilators within up to 28 days of hospitalization

Measure: Ventilator-Free Days

Time: 28 days or hospital discharge, whichever is earlier

Description: Measure the fraction of inspired oxygen (FiO2) and its usage within the body during intensive care, measured using fNIRS (Functional Near Infrared Spectroscopy).

Measure: Change in Oxygenation Index (OI)

Time: 28 days

Description: Measuring respiratory mechanics in ventilated patients [plateau pressure (Pplat)-positive end-expiratory pressure]

Measure: Plat-PEEP

Time: 28 days

Description: 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) Scores

Time: 28 days

Description: The SIT is a self-administered 40-item test involving microencapsulated (scratch-and-sniff) odors with a forced-choice design. The test has a total score ranging from 0-40 Follows scoring key for evaluation. The higher score indicates better outcome.

Measure: Small Identification Test (SIT) scores

Time: At baseline, day 18 and day 28.

Description: As assessed via serum blood samples.

Measure: Troponin I levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: C-Reactive Protein levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Arachidonic Acid (AA)/Eicosapentaenoic Acid (EPA) Ratio

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: D-dimer levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: 25-Hydroxy Vitamin D levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Alloantibodies levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Blood white cell count

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Platelets count

Time: Baseline, 28 days
41 Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection: A Phase 2a Clinical Trial

The global pandemic COVID-19 has overwhelmed the medical capacity to accommodate a large surge of patients with acute respiratory distress syndrome (ARDS). In the United States, the number of cases of COVID-19 ARDS is projected to exceed the number of available ventilators. Reports from China and Italy indicate that 22-64% of critically ill COVID-19 patients with ARDS will die. ARDS currently has no evidence-based treatments other than low tidal ventilation to limit mechanical stress on the lung and prone positioning. A new therapeutic approach capable of rapidly treating and attenuating ARDS secondary to COVID-19 is urgently needed. The dominant pathologic feature of viral-induced ARDS is fibrin accumulation in the microvasculature and airspaces. Substantial preclinical work suggests antifibrinolytic therapy attenuates infection provoked ARDS. In 2001, a phase I trial 7 demonstrated the urokinase and streptokinase were effective in patients with terminal ARDS, markedly improving oxygen delivery and reducing an expected mortality in that specific patient cohort from 100% to 70%. A more contemporary approach to thrombolytic therapy is tissue plasminogen activator (tPA) due to its higher efficacy of clot lysis with comparable bleeding risk 8. We therefore propose a phase IIa clinical trial with two intravenous (IV) tPA treatment arms and a control arm to test the efficacy and safety of IV tPA in improving respiratory function and oxygenation, and consequently, successful extubation, duration of mechanical ventilation and survival.

NCT04357730
Conditions
  1. Severe Acute Respiratory Syndrome
  2. Respiratory Failure
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Alteplase 50 MG [Activase]
  2. Drug: Alteplase 100 MG [Activase]
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome

Primary Outcomes

Description: Ideally, the PaO2/FiO2 will be measured with the patient in the same prone/supine position as in baseline, as change in positions may artificially reduce the improvement attributable to the study drug. However, given the pragmatic nature of the trial, the prone/supine position will be determined by the attending physician, in which case, we will use as an outcome the PaO2/FiO2 closest to the 48 hours obtained prior to the change in position as the outcome.

Measure: PaO2/FiO2 improvement from pre-to-post intervention

Time: at 48 hours post randomization

Secondary Outcomes

Description: Achievement of PaO2/FiO2 ≥ 200 or 50% increase in PaO2/FiO2 (whatever is lower)

Measure: Achievement of PaO2/FiO2 ≥ 200 or 50% increase in PaO2/FiO2

Time: at 48 hours post randomization

Description: This score is based on seven clinical features (respiration rate, hypercapnic respiratory failure, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness) and determines the degree of illness of a patient and prompts critical care intervention.

Measure: National Early Warning Score 2 (NEWS2)

Time: at 48 hours post randomization

Description: The ordinal scale is an assessment of the clinical status 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 - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. (combined items 7 and 8 as our study is limited to hospital).

Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale

Time: at 48 hours post randomization

Description: 48 hour mortality for hospitalized patients

Measure: 48 hour in-hospital mortality

Time: at 48 hours post randomization

Description: 14 days mortality for hospitalized patients

Measure: 14 days in-hospital mortality

Time: 14 days post randomization

Description: 28 days mortality for hospitalized patients

Measure: 28 days in-hospital mortality

Time: 28 days post randomization

Description: ICU-free days will be calculated based on (28 - number of days spent in the ICU) formula

Measure: ICU-free days

Time: 28 days of hospital stay or until hospital discharge (whichever comes first)

Description: In-hospital coagulation-related events include bleeding, stroke, myocardial infarction and venous thromboembolism (VTE). In-hospital coagulation-related event-free (arterial and venous) days will be calculated based on (28 - number of days without coagulation-related event) formula.

Measure: In-hospital coagulation-related event-free (arterial and venous) days

Time: 28 days of hospital stay or until hospital discharge (whichever comes first)

Description: Ventilator-free days will be calculated based on (28 - number of days on mechanical ventilation) formula.

Measure: Ventilator-free days

Time: 28 days of hospital stay or until hospital discharge (whichever comes first)

Description: Calculated for patients who was on a mechanical ventilation any period of time during hospitalization. The extubation will be considered successful if no re-intubation occurred for more than 3 days have passed after the initial extubation.

Measure: Successful extubation

Time: Day 4 after initial extubation

Description: Calculated for patients who was on paralytics at the time of randomization. The weaning will be considered successful if no paralytics were used for more than 3 days have passed after termination of paralytics.

Measure: Successful weaning from paralysis

Time: Day 4 after initial termination of paralytics

Description: Is counted for the patients who was alive at the time of discharge.

Measure: Survival to discharge

Time: 28 days of hospital stay or until hospital discharge (whichever comes first)
42 Impact of Dexmedetomidine Infusion on the Time Course and Outcomes of Acute Respiratory Distress Syndrome (ARDS) in Patients Affected by the SARS-CoV-2 (COVID-19) Admitted to Critical Care Unit

A continuous infusion of Dexmedetomidine (DEX) will be administered to 80 patients admitted to Critical Care because of signs of Respiratory Insufficiency requiring non-invasive ventilation. Measurements of respiratory performance and quantification of cellular and molecular inflammatory mediators. The primary outcome will be the avoidance of mechanical ventilation with secondary outcomes duration of mechanical ventilation, avoidance of delirium after sedation and association of mediators of inflammation to outcomes. Outcomes will be compared to a matched historical control (no DEX) series

NCT04358627
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Inflammation
  3. Dexmedetomidine
  4. Cytokine Storm
  5. Delirium, Emergence
Interventions
  1. Drug: Dexmedetomidine Injectable Product
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Delirium Emergence Delirium Syndrome Inflammation

Primary Outcomes

Description: (Presence/Absence) requirement of mechanical ventilation

Measure: Mechanical ventilation

Time: expected within first three days (non conclusive due to lack of evidence yet)

Secondary Outcomes

Description: Duration of mechanical ventilation if it is required (hours from the start)

Measure: Duration of mechanical ventilation

Time: expected within first seven days (non conclusive due to lack of evidence yet)

Description: Delirium criteria as defined in DSM-4

Measure: Delirium on recovery from sedation

Time: First 24 hours after retiring dexmedetomidine sedation
43 Evaluation of Prone Position in Conscious Patients on Nasal High-flow Oxygen Therapy for COVID-19 Disease Induced Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome (ARDS) induces high mortality, particularly in the context of COVID-19 disease. Preliminary data from patients with ARDS related to COVID-19 disease appear to show significant effectiveness of prone positioning in intubated patients in terms of oxygenation as well as nasal high flow therapy before intubation. It should be noted that in Jiangsu province, secondarily affected, nasal high flow combined with the prone position was successfully integrated into care protocols. The investigators hypothesize that the combined application of nasal high flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for tracheal intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources. Investigators hypothesize that the combined application of nasal high-flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources.

NCT04358939
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Other: Prone decubitus
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Therapeutic failure is defined by death or intubation or use of non-invasive ventilation at two pressure levels.

Measure: Therapeutic failure within 14 days of randomization

Time: From randomization to day 14

Secondary Outcomes

Description: Therapeutic failure is defined by death or intubation or use of non-invasive ventilation at two pressure levels.

Measure: Therapeutic failure within 28 days of randomization

Time: From randomization to day 28

Measure: Timeframe of intubation or death

Time: From randomization to day 28

Measure: Timeframe of therapeutic escalation (in case of non-invasive ventilation at two pressure levels)

Time: From randomization to day 28

Measure: Evolution of oxygenation (PaO2/FiO2 ratio or SpO2/FiO2 surrogate) over the 14 days following randomization

Time: From randomization to day 14

Measure: Evolution of the SpO2/FiO2 ratio during the first prone session

Time: From randomization to day 1

Description: ROX index is the ratio of pulse oximetry (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate.

Measure: Evolution of the ROX index during the first prone session

Time: From randomization to day 1

Description: Score reaches from 1 to 7, 7 indicates worse outcome

Measure: Evolution of the World Health Organization disease severity score of COVID

Time: From randomization to day 28

Description: Comfort evaluted by the patient through a visual analogical scale

Measure: Patient comfort before, during and after the first prone position session

Time: From randomization to day 1

Measure: Occurrence of skin lesions on the anterior surface of the body

Time: From randomization to day 28

Description: Invasive devices include : central and peripheric vascular catheters, tracheal tube, urinary catheter, chest tubes.

Measure: Displacement of invasive devices during reversals

Time: From randomization to day 28

Measure: Days of nasal High-Flow therapy use in the general population, in non-intubated patients and in intubated patients

Time: From randomization to day 28

Measure: Days spent in the intensive care unit and in the hospital

Time: From randomization to day 28

Measure: Mortality in the intensive care unit and in the hospital

Time: From randomization to day 28

Measure: Ventilator-free-days within 28 days of randomization

Time: From randomization to day 28
44 The Effect of Prone Positioning on Lung Aeration and Ventilation-perfusion Matching in Mechanically Ventilated Patients With Coronavirus Disease Related Acute Respiratory Distress Syndrome

The consensus therapeutic strategy implies that COVID patients with acute lung injury due to coronavirus are routinely placed in prone position in an attempt to improve oxygenation by increasing ventilation homogeneity. The purpose of the study is to quantify with the electrical impedance tomography (EIT) the changes in the ventilation and aeration in the dorsal regions of the lung when the patient is placed in prone position.

NCT04359407
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
  2. Electric Impedance
  3. Prone Positioning
Interventions
  1. Other: Prone positioning
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: Change in the ratio of tidal electrical impedance variation in the dorsal and total lung areas

Measure: Tidal electrical Impedance

Time: One hour before turning to prone or supine positioning

Secondary Outcomes

Description: Changes in intrapulmonary shunt fraction

Measure: Intrapulmonary shunt

Time: One hour before turning to prone or supine positioning

Description: Changes in the phase three slope of the volumetric capnogram

Measure: Volumetric capnography

Time: One hour before turning to prone or supine positioning
45 COVID-19: Ruxolitinib for the Treatment of cytokinE Storm resPiratory dIstREss Syndrome. RESPIRE Study

It is an observational, cohort, retrospective, monocentric, non-profit study. The primary objective is to evaluate the efficacy and safety of ruxolitinib in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours.

NCT04361903
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
Interventions
  1. Drug: Ruxolitinib Oral Tablet
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Syndrome

Primary Outcomes

Description: Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours

Measure: Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19

Time: 15 days

Secondary Outcomes

Description: ABG (arterial Blood Gas): pH as SI Unit, every 12 hours and in any case in the presence of significant clinical variations.

Measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pH

Time: 15 days

Description: ABG (arterial Blood Gas): pO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations.

Measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pO2

Time: 15 days

Description: ABG (arterial Blood Gas): pCO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations.

Measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pCO2

Time: 15 days

Description: PaO2 / FiO2, SatO2 ratio. Vital parameters and respiratory function every 12 hours and in any case in the presence of significant clinical variations.

Measure: Improvement of respiratory performance - ratio values

Time: 15 days

Description: every 24 hours D-Dimer value in mgr/ml

Measure: Evaluation of known adverse events related to the use of the drug - D-Dimer

Time: 15 days

Description: every 24 hours fibrinogen value in mg/dl

Measure: Evaluation of known adverse events related to the use of the drug - fibrinogen

Time: 15 days

Description: every 24 hours transaminases value in U/L

Measure: Evaluation of known adverse events related to the use of the drug - transaminases

Time: 15 days

Description: every 24 hours aPTT value in seconds

Measure: Evaluation of known adverse events related to the use of the drug - aPTT

Time: 15 days

Description: every 24 hours INR value in %

Measure: Evaluation of known adverse events related to the use of the drug - INR

Time: 15 days

Description: every 24 hours glycemia value in mg/dl

Measure: Evaluation of known adverse events related to the use of the drug - glycemia

Time: 15 days

Description: every 24 hours creatinine serum value in mg/dl

Measure: Evaluation of known adverse events related to the use of the drug - creatinine

Time: 15 days

Description: Total leucocyte as CBC x10e)/L

Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes count

Time: 15 days

Description: formula % on total leucocyte

Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes formula

Time: 15 days

Description: Thoracic imaging, every 48 h: presence, extension and dimension on lung thickening - Chest CT at start and end of treatment, Time elapsed between the onset of clinical symptoms and hospitalization.

Measure: Evaluation of the epidemiological parameters: Chest CT

Time: 15 days

Description: Thoracic imaging: every day: presence and number of line B every 48 hours.Time elapsed between the onset of clinical symptoms and hospitalization.

Measure: Evaluation of the epidemiological parameters: Eco Chest

Time: 15 days

Description: Thoracic imaging: presence, extension and dimension on lung thickening - Chest X-ray, Time elapsed between the onset of clinical symptoms and hospitalization.

Measure: Evaluation of the epidemiological parameters: CHEST X-ray

Time: 15 days

Description: Monitoring of serum cytokines (IL-6 in pgr/dL, TNF in pgr/dL) every 48 h

Measure: Monitoring of Serum levels of cytokines before and every 48 h from start to to end of treatment

Time: 15 days

Description: Number of AE grade 1 to 4

Measure: Monitoring incidence of treatment Emergent Adverse Events of ruxolitinib therapy

Time: 15 days
46 Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Canakinumab on Cytokine Release Syndrome in Patients With COVID-19-induced Pneumonia (CAN-COVID)

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 patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS).

NCT04362813
Conditions
  1. Pneumonia and Cytokine Release Syndrome (Covid-19)
Interventions
  1. Drug: Canakinumab
  2. Drug: Placebo
MeSH:Pneumonia Syndrome
HPO:Pneumonia

Primary Outcomes

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 29

Secondary Outcomes

Description: 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 weeks

Description: Clinical chemistry measurement in a blood sample.

Measure: Ratio to baseline in the C-reactive protein (CRP)

Time: Baseline, Day 29

Description: Clinical chemistry measurement in a blood sample.

Measure: Ratio to baseline in the serum ferritin

Time: Baseline, Day 29

Description: Clinical chemistry measurement in a blood sample.

Measure: Ratio to baseline in the D-dimer

Time: Baseline, Day 29

Description: 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 days
47 Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19

Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.

NCT04365985
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Severe Acute Respiratory Syndrome (SARS)
  4. Coronavirus Infections
Interventions
  1. Drug: Naltrexone
  2. Drug: Ketamine
  3. Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)

Measure: Progression of oxygenation needs

Time: up to 1 month

Secondary Outcomes

Description: Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.

Measure: Renal failure

Time: up to 1 month

Description: Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits

Measure: Liver failure

Time: up to 1 month

Description: Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)

Measure: Cytokine Storm

Time: up to 1 month

Description: Count of participants who die from COVID-19

Measure: Mortality

Time: up to 1 month post hospital discharge

Description: Length of hospital stay in days

Measure: Length of hospital stay

Time: up to 1 month

Description: Count of patients admitted to the ICU at any time during index hospitalization

Measure: Intensive Care Unit (ICU) admission

Time: up to 1 month

Description: Length of ICU stay in days

Measure: Intensive Care Unit (ICU) duration

Time: up to 1 month

Description: Count of participants requiring intubation

Measure: Intubation

Time: up to 1 month

Description: Length of intubation, measured in days

Measure: Intubation duration

Time: up to 1 month

Description: Time measured in days from hospital admission to determination patient is stable for discharge

Measure: Time until recovery

Time: up to 1 month
48 Intermediate-size Expanded Access of Remestemcel-L, Ex-vivo Cultured Adult Human Mesenchymal Stromal Cells for Acute Respiratory Distress Syndrome Due to COVID-19 Infection

The objectives of this intermediate-size expanded access protocol are to assess the safety and efficacy of remestemcel-L in participants with ARDS due to coronavirus infection 2019 (COVID-19).

NCT04366830
Conditions
  1. Moderate to Severe Acute Respiratory Distress Syndrome Associated With COVID-19
Interventions
  1. Drug: Remestemcel-L
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

49 Prevention and Treatment With Calcifediol of COVID-19 Coronavirus-induced Acute Respiratory Syndrome (SARS)

The administration of Calcifediol in patients with COVID-19, will reduce the development of SARS and the worsening of the various phases of the syndrome. Reducing at least 25% in ICU admission and death from the process, reducing days of hospitalization, facilitating the recovery of the same, acting significantly and positively, in any of its phases throughout the natural history of illness. As a treatment with extensive experience of clinical use, safe, inexpensive, and potentially very effective, it will have a highly efficient cost-benefit impact on the prevention of SARS.

NCT04366908
Conditions
  1. SARS-CoV 2
  2. COVID19
  3. SARS (Severe Acute Respiratory Syndrome)
  4. Cytokine Release Syndrome
  5. Cytokine Storm
Interventions
  1. Drug: BAT + Calcifediol
  2. Drug: BAT
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

Primary Outcomes

Description: Proportion of subjects who enter the Intensive Care Unit

Measure: Admission to Intensive Care Unit

Time: At day 28.

Description: Proportion of subjects who die.

Measure: Death

Time: At day 28.

Secondary Outcomes

Description: Compare the time (in days) at discharge in newly hospitalized patients on non-invasive ventilation.

Measure: Time from onset of symptoms to discharge of patients in conventional hospitalization

Time: At day 28.

Description: In patients who, in the course of their evolution, required admission with mechanical ventilation in the ICU, time until admission to Intensive Care Unit

Measure: ICU - Time until admission

Time: At day 28.

Description: In patients who, in the course of their evolution, required admission with mechanical ventilation in the ICU, time until mechanical ventilation is removed.

Measure: ICU - Time mechanical ventilation is removed

Time: At day 28.

Description: Evaluation of the inflammatory markers related to IL disease. Blood samples will be collected and assessed in order to evaluate interleukins related with the interleukin storm using immunological tests.

Measure: Evaluation of the inflammatory markers related with the disease

Time: At day 28.

Description: Evaluation of the Vitamin D metabolites.

Measure: Vitamin D metabolites

Time: At day 28.

Description: Compare the evolution in SatO2

Measure: Evolution in SatO2

Time: At day 28.

Description: Compare the evolution in the Sat O2/FiO2 ratio

Measure: Evolution in the Sat O2/FiO2 ratio.

Time: At day 28.

Description: Compare the evolution in the degree of dyspnea using the analog Borg scale

Measure: Evolution in the degree of dyspnea

Time: At day 28.

Description: Compare the evolution of radiological findings by simple radiology in the recruited subjects since their beginning in the trial until they end the trial

Measure: Evolution of the improvement of radiological findings by simple radiology

Time: At day 28.

Description: Incidence of adverse events related to medication and its administration.

Measure: Incidence of adverse events

Time: At day 28.

Description: Incidence in the appearance of hemorrhagic or thrombotic phenomena.

Measure: Appearance of hemorrhagic or thrombotic phenomena

Time: At day 28.
50 A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared With Best Supportive Care in Patients With COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome

This 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.

NCT04369469
Conditions
  1. COVID-19 Severe Pneumonia
  2. Acute Lung Injury
  3. Acute Respiratory Distress Syndrome
  4. Pneumonia, Viral
Interventions
  1. Biological: Ravulizumab
  2. Other: Best Supportive Care
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

Measure: Survival (based on all-cause mortality) at Day 29

Time: Baseline, Day 29

Secondary Outcomes

Measure: Number of days free of mechanical ventilation at Day 29

Time: Baseline, Day 29

Measure: Duration of intensive care unit stay at Day 29

Time: Baseline, Day 29

Measure: Change from baseline in Sequential Organ Failure Assessment at Day 29

Time: Baseline, Day 29

Measure: Change from baseline in SpO2/FiO2 at Day 29

Time: Baseline, Day 29

Measure: Duration of hospitalization at Day 29

Time: Baseline, Day 29

Measure: Survival (based on all-cause mortality) at Day 60 and Day 90

Time: Baseline, Day 60, Day 90
51 Mesenchymal Stem Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome

The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.

NCT04371393
Conditions
  1. Mesenchymal Stromal Cells
  2. Remestemcel-L
  3. Acute Respiratory Distress Syndrome
  4. COVID
Interventions
  1. Biological: Remestemcel-L
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of all-cause mortality within 30 days of randomization.

Measure: Number of all-cause mortality

Time: 30 days

Secondary Outcomes

Description: Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.

Measure: Number of days alive off mechanical ventilatory support

Time: 60 days

Description: Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.

Measure: Number of adverse events

Time: 30 days

Measure: Number of participants alive at day 7

Time: 7 days

Measure: Number of participants alive at day 14

Time: 14 days

Measure: Number of participants alive at day 60

Time: 60 days

Measure: Number of participants alive at day 90

Time: 90 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 7

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 7 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 14

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 14 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 21

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 21 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 30

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 30 days

Description: Change from baseline of the severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

Measure: Change from baseline of the severity of ARDS

Time: baseline and 7 days

Description: Change from baseline of the severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

Measure: Change from baseline of the severity of ARDS

Time: baseline and 14 days

Description: Change from baseline of the severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

Measure: Change from baseline of the severity of ARDS

Time: baseline and 21 days

Description: Change from baseline of the severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

Measure: Change from baseline of the severity of ARDS

Time: baseline and 30 days

Description: Hospital length of stay

Measure: Length of stay

Time: 12 months

Description: Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 7 days

Description: Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 14 days

Description: Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 21 days

Description: Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 30 days

Description: Changes from baseline in serum hs-CRP concentration at days 7

Measure: Change in serum hs-CRP concentration

Time: baseline and 7 days

Description: Changes from baseline in serum hs-CRP concentration at days 14

Measure: Change in serum hs-CRP concentration

Time: baseline and 14 days

Description: Changes from baseline in serum hs-CRP concentration at days 21

Measure: Change in serum hs-CRP concentration

Time: baseline and 21 days

Description: Changes from baseline in serum hs-CRP concentration at days 30

Measure: Change in serum hs-CRP concentration

Time: baseline and 30 days

Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 7 days

Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 14 days

Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 21 days

Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 30 days

Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 7 days

Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 14 days

Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 21 days

Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 30 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 7 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 7 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 14 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 14 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 21 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 21 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 30 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 30 days
52 Interventional Study to Evaluate the Efficacy of Therapeutic Plasma Exchange (TPE) Alone or in Combination With Ruxolitinib in COVID-19 Positive Patients With PENN Grade 2, 3, 4 Cytokine Released Syndrome (CRS)

This protocol will evaluate the efficacy of Therapeutic Plasma Exchange alone or in combination with ruxolitinib in COVID positive patients with PENN grade 2, 3, 4 cytokine release syndrome. It is hypothesized that dual intervention of acute apheretic depletion of cytokines and concomitant suppression of production will produce superior amelioration of the cytokine load and to help to prevent cytokine load rebound. This protocol is envisioned as a pilot study (n=20) for hypothesis generation for future investigation.

NCT04374149
Conditions
  1. Cytokine Release Syndrome
  2. COVID19
Interventions
  1. Procedure: Therapeutic Plasma Exchange
  2. Drug: Ruxolitinib
MeSH:Syndrome

Primary Outcomes

Description: Defined as greater than or equal to 33% decrease in cytokine load in one-third or more participants

Measure: Overall Response Rate

Time: 14 days
53 Assessment of Extra Vascular Lung Water and Pulmonary Permeability by Transpulmonary Thermodilution in Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Acute 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.

NCT04376905
Conditions
  1. COVID-19
  2. Pneumonia
  3. Acute Respiratory Distress Syndrome
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

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 3

Secondary Outcomes

Description: 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 3

Description: 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 3
54 Comparison of the Efficacy and Safety of Tocilizumab Versus Methylprednisolone in the Cytokine Release Syndrome of Patients With COVID-19. A Prospective Randomized Controlled Phase II Trial

This study compare the efficacy and safety of tocilizumab versus methylprednisolone in the cytokine release syndrome of patients with COVID-19

NCT04377503
Conditions
  1. Cytokine Release Syndrome
  2. Covid-19
Interventions
  1. Drug: Tocilizumab 180 MG/ML
  2. Drug: Methylprednisolone Sodium Succinate
MeSH:Syndrome

Primary Outcomes

Description: A seven-category ordinal scale consisting of: 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 - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Measure: Patient clinical status 15 days after randomization

Time: 15 days after randomization

Secondary Outcomes

Description: Improvement in PaO2/FIO2

Measure: Improving oxygenation

Time: 15 days

Description: Improvement in the computed tomography between D0 and D10 after randomization

Measure: Thorax CT improvement

Time: 10 days

Description: Duration o ICU stay in days

Measure: ICU length of stay

Time: 28 days

Description: Days of mechanical ventilation

Measure: Duration of mechanical ventilation

Time: 28 days

Description: AKI according to Kidney Disease Improving Global Outcomes (KDIGO)

Measure: Incidence of acute kidney (AKI) with necessity of renal replacement therapy

Time: 15 days
55 A Study of Trans Crocetin in Patients With Acute Respiratory Distress Syndrome Due to COVID-19 Disease

This is an open label phase II study of treatment with LEAF-4L7520 and LEAF-4L6715 in patients who experience severe acute respiratory distress syndrome (ARDS) and are receiving artificial respiratory support due to COVID-19. The purpose of this study is to evaluate the improvement in PaO2/FiO2 by more than 25% in two cohorts of patients treated with LEAF-4L7520 or LEAF-4L6715.

NCT04378920
Conditions
  1. COVID19
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: LEAF-4L6715
  2. Drug: LEAF-4L7520
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: proportion of patients showing an increase of at least 25% of PaO2/FiO2 ratio

Time: 24 hours

Secondary Outcomes

Measure: proportion of patients with a PaO2/FiO2 ratio above 200 mm Hg

Time: 24, 48 and 72 hours

Measure: all cause mortality

Time: 28 days
56 Effectiveness and Safety of Convalescent Plasma Therapy on COVID-19 Patients With Acute Respiratory Distress Syndrome in Referral Hospitals in Indonesia

Corona virus disease 2019 (COVID-19) has been declared as a Pandemic by the World Health Organization (WHO). According to WHO report on March 31st 2020, globally COVID-19 have infected over 750,000 people and caused over 36,000 deaths with case fatality rate of 4.85%. In Indonesia, COVID-19 have infected 1,414 people and caused 122 deaths with case fatality rate of 8.63%. In severe cases, COVID-19 causes complications, such as acute respiratory distress syndrome (ARDS), sepsis, septic shock, and multi-organ dysfunction syndrome (MODS), where age and comorbid illnesses as a major factor to these complications. Up to this point there are several promising therapies for COVID-19 but is not yet recommended and in need of further research. The use of convalescent plasma has been approved by the US Food and Drug Administration (FDA) through the scheme of emergency investigational new drug (eIND). This method has been used as the treatment in several outbreak or plague cases over the years, such as the flu epidemic in 1918, polio, measles, mumps, SARS (severe acute respiratory syndrome), EVD (Ebola virus disease) and MERS (middle-eastern respiratory syndrome) and this treatment shows better outcome. Several case report on the use of convalescent plasma for COVID-19 patients with ARDS and mechanical ventilation has been reported and shows promising outcome. Nevertheless, larger and multicenter research need to be done to assess and evaluate the effectiveness and safety of convalescent plasma therapy on for COVID-19 patients with ARDS.

NCT04380935
Conditions
  1. COVID
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Convalescent plasma
  2. Drug: Standard of care
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Proportion of all-cause mortality

Measure: All-cause mortality

Time: up to 28 days

Secondary Outcomes

Description: Mean length of stay in intensive care unit

Measure: Length of stay in intensive care unit

Time: up to 28 days

Description: Mean duration of mechanical ventilation

Measure: Duration of mechanical ventilation

Time: up to 28 days

Description: Mean change from baseline using time series analysis

Measure: Body temperature (degree in Celsius)

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: The Sequential Organ Failure Assessment (SOFA) Score

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: PAO2/FIO2 ratio

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: C-Reactive Protein (CRP) in mg/L

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: D-Dimer in ng/mL

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: Procalcitonin in ng/mL

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: Interleukin 6 (IL-6) in pg/mL

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Number of participants with allergic/ anaphylaxis transfusion reaction

Measure: Allergic/ anaphylaxis transfusion reaction

Time: 24 hours post-transfusion

Description: Number of participants with Hemolytic transfusion reaction

Measure: Hemolytic transfusion reaction

Time: 24 hours post-transfusion

Description: Number of participants with Transfusion Related Acute Lung Injury

Measure: Transfusion Related Acute Lung Injury

Time: 24 hours post-transfusion

Description: Number of participants with Transfusion associated Circulatory Overload

Measure: Transfusion associated Circulatory Overload

Time: 24 hours post-transfusion
57 A Prospective, Randomized, Controlled Study Assessing Vagus Nerve Stimulation in CoViD-19 Respiratory Symptoms (SAVIORII)

The study is a prospective, randomized, controlled investigation designed for comparison of two groups for the reduction of respiratory distress in a CoViD-19 population, using gammaCore Sapphire (nVNS) plus standard of care (active) vs. standard of care alone (SoC), the control group. The gammaCore® (nVNS) treatments will be used acutely and prophylactically. The active and control groups will be diseased and severity matched. The primary objective is to reduce initiation of mechanical ventilation in patients with CoViD-19 compared to the control group. Secondary objectives are to evaluate cytokine trends/prevent cytokine storms, evaluate supplemental oxygen requirements, decrease mortality of CoViD-19 patients and to delay the onset of mechanical ventilation.

NCT04382391
Conditions
  1. COVID
  2. Corona Virus Infection
  3. Respiratory Failure
  4. Respiratory Distress Syndrome, Adult
  5. ARDS, Human
  6. SARS (Severe Acute Respiratory Syndrome)
Interventions
  1. Device: gammaCore® Sapphire (non-invasive vagus nerve stimulator)
  2. Other: Standard of care therapies
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome Signs and Symptoms, Respiratory

Primary Outcomes

Description: measure the change (in hours) between the control group and treatment group

Measure: change in initiation of mechanical ventilation in patients with CoViD-19 compared to the control group.

Time: From the time of randomization until the time of initiation of mechanical ventilation, assessed up to day of discharge or death, whichever occurs first, assessed up to 3 months

Secondary Outcomes

Description: measure the changes in the serum/plasma concentrations of TH1 and TH2-type cytokines

Measure: evaluate cytokine trends

Time: From the time of initial blood draw until the time of final blood draw, assessed up to date of mechanical ventilation, death, or discharge from hospital, whichever occurs first,assessed up to 3 months

Description: compare the difference in oxygen requirements (liters/min) between the control group and active group for patients admitted to the hospital for CoViD-19.

Measure: evaluate supplemental oxygen requirements

Time: From the time of randomization, assessed up to time of mechanical ventilation, day of discharge or death, whichever occurs first,assessed up to 3 months

Description: measure the change (in hours) to death between control group and treatment group

Measure: decrease mortality of CoViD-19 patients

Time: From the time or randomization until the date of death from any cause, assessed up to day of discharge or death,assessed up to 3 months

Description: measure the change (in hours) to time of mechanical ventilation between control group and treatment group

Measure: delay onset of ventilation

Time: From the time of randomization until the time of initiation of mechanical ventilation, assessed up to day of discharge or death, whichever occurs first,assessed up to 3 months
58 Outcome of COVID-19 Patients After Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A Multicenter European Study

This study aims to investigate outcomes and predictors of outcome after extracorporeal membrane oxygenation (ECMO) therapy for severe acute respiratory syndrome (ARDS) in COVID-19 patients.

NCT04383678
Conditions
  1. COVID-19
  2. Extracorporeal Membrane Oxygenation Complication
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Device: Extracorporeal membrane oxygenation
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: In-hospital mortality

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Secondary Outcomes

Measure: Death on ECMO

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Stroke

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Blood stream infection

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Lung complications requiring surgical treatment

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Blood transfusion

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Acute kidney injury

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Duration of mechanical ventilation

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Deep vein thrombosis

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Pulmonary embolism

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Length of ICU stay

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Length of hospital stay

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Death after hospital discharge

Time: During index hospital stay follow-up until 1 year after ECMO initiation
59 Inhaled Sedation in COVID-19-related Acute Respiratory Distress Syndrome (ISCA): an International Research Data Study in the Recent Context of Widespread Disease Resulting From the 2019 (SARS-CoV2) Coronavirus Pandemics (COVID-19)

The authors hypothesized that inhaled sedation, either with isoflurane or sevoflurane, might be associated with improved clinical outcomes in patients with COVID-19-related ARDS, compared to intravenous sedation. The authors therefore designed the "Inhaled Sedation for COVID-19-related ARDS" (ISCA) non-interventional, observational, multicenter study of data collected from the patients' medical records in order to: 1. assess the efficacy of inhaled sedation in improving a composite outcome of mortality and time off the ventilator at 28 days in patients with COVID-19-related ARDS, in comparison to a control group receiving intravenous sedation (primary objective), 2. investigate the effects of inhaled sedation, compared to intravenous sedation, on lung function as assessed by gas exchange and physiologic measures in patients with COVID-19-related ARDS (secondary objective), 3. report sedation practice patterns in critically ill patients during the COVID-19 pandemics (secondary objective).

NCT04383730
Conditions
  1. Critically Illness
  2. Sedation
  3. Invasive Mechanical Ventilation
  4. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Intravenous sedation
  2. Drug: Inhaled sedation
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Ventilator-free days to day 28 are defined as the number of days from the time of initiating unassisted breathing to day 28 after intubation, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a patient was receiving assisted breathing at day 27 or died prior to day 28, VFDs will be zero. Patients transferred to another hospital or other health care facility will be followed to day 28 to assess this endpoint.

Measure: Number of days off the ventilator (VFD28, for ventilator-free days), taking into account death as a competing event

Time: Day 28 after inclusion

Secondary Outcomes

Description: All-cause mortality

Measure: All-cause mortality

Time: Days 7, 14, and 28 after inclusion

Description: Ventilator-free days to days 7 and 14 are defined as the number of days from the time of initiating unassisted breathing to day 7 and 14 after intubation, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to days 7 and 14 If a patient returns to assisted breathing and subsequently achieves unassisted breathing to days 7 and 14 , VFDs will be counted from the end of the last period of assisted breathing to days 7 and 14. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a patient was receiving assisted breathing at day 6 or 13 or died prior to days 7 and 14, respectively,VFDs to days 7 and 14 will be zero. Patients transferred to another hospital or other health care facility will be followed to days 7 and 14 to assess this endpoint.

Measure: Ventilator-free days

Time: Days 7 and 14 after inclusion

Description: Number of days alive and not in the ICU from inclusion to day 28

Measure: ICU-free days

Time: Day 28 after inclusion

Description: Total duration of controlled mechanical ventilation to day 28

Measure: Duration of invasive mechanical ventilation

Time: Day 28 after inclusion

Description: Total duration of controlled mechanical ventilation to day 28

Measure: Duration of controlled mechanical ventilation

Time: Day 28 after inclusion

Description: Arterial hypoxemia, as assessed by the partial pressure of arterial oxygen-to-fraction of inspired oxygen ratio (PaO2/FiO2)

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Partial pressure of arterial carbon dioxide (PaCO2)

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Inspiratory plateau pressure

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Driving pressure

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Mode of mechanical ventilation (assisted versus controlled)

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: If available, 100 ms occlusion pressure (P0.1), a marker of respiratory drive

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Development of pneumothorax

Measure: Development of complications

Time: Day 7 from inclusion

Description: Supraventricular tachycardia

Measure: Development of complications

Time: Day 7 from inclusion

Description: New onset atrial fibrillation

Measure: Development of complications

Time: Day 7 from inclusion

Description: Total duration (in days) of vasopressor use

Measure: Duration of vasopressor use

Time: Day 28 after inclusion

Description: Total duration (in days)of renal replacement therapy

Measure: Duration of renal replacement therapy

Time: Day 28 after inclusion

Description: Adjuvant therapies are defined as: prone position, recruitment maneuvers, inhaled nitric oxide, inhaled epoprostenol sodium, high frequency ventilation, ECMO, neuromuscular blockade

Measure: Duration (in days) of any adjuvant therapies

Time: Day 7 from inclusion

Description: Number of days with continuous neuromuscular blockade

Measure: Duration of continuous neuromuscular blockade

Time: Day 28 from inclusion

Description: Sedation drug(s) used (name(s))

Measure: Type of sedation practices

Time: Day 28 from inclusion

Description: Number of days with sedation

Measure: Duration of sedation practices

Time: Day 28 from inclusion

Description: If inhaled sedation, device used to deliver it

Measure: Modalities of sedation practices

Time: Day 28 from inclusion
60 Characterization of the Clinical, Biological and Histological Pulmonary and Renal Damage Associated With the SARS-CoV-2 Syndrome in Patients Admitted in the Intensive Care Unit

Renal damage in patients hospitalized for ARDS in the ICU can also be related to multiple causes including, but not limited to, the consequences of hemodynamic fluctuations in these patients or the use of nephrotoxic drugs responsible for acute post-ischemic or toxic tubular necrosis. Frequently observed abnormalities of cioagumation may also have a potential impact on renal structures, particularly glomerular capillaries. The researchers wish to characterize and phenotype the renal impairment of patients hospitalized in intensive care with tables of severe Covid19 infections in ARDS: clinical, biological and histological (by performing post-mortem biopsies). Translated with www.DeepL.com/Translator (free version)

NCT04385004
Conditions
  1. Acute Respiratory Distress Syndrome
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: Analysis of Clinical, Biological and Histological Pulmonary and Renal Impairment Related to SARS-CoV-2

Time: 1 month
61 COVID-19 Hyperinflammation Syndrome (COV-HI): Protocol for a Rapidly Executed Cohort Study

Based on emerging experience and trials from countries affected early by the COVID-19 (COV19) pandemic, there is evidence that a subgroup of severely affected people develop a hyperinflammatory (HI) syndrome (COV-HI). Trials are in progress of cytokine inhibition and other immune modulation to treat COV-HI. This proposal aims to use a rapidly executed cohort study to characterise the clinical phenotypes of COV-HI in patients in the UK through an established and nimble network of clinicians and scientists with broad experience of identifying and treating HI. The aim is to confirm the COV-HI clinical phenotype and using routine data to try to infer the inflexion point where COV-HI emerges. This would enable refinement of the proposed treatment algorithm and translates to routine clinical practice to improve the outlook for COV-HI.

NCT04385069
Conditions
  1. COV-HI
  2. COVID-19
  3. COVID-19 (COV) Hyperinflammatory (HI) Syndrome
MeSH:Syndrome

Primary Outcomes

Description: Confirm positive diagnosis within electronic hospital records and collate selected demographic data from eligible patients identified.

Measure: To collect retrospective demographic information on 500 people admitted to selected hospital sites across the UK with a COVID-19 diagnosis confirmed through positive laboratory PCR swab.

Time: within 3 months

Description: Research staff will review the electronic patient record for all eligible participants and record the results of each patients routine blood tests, chest x-rays, echos and any other associated clinical investigations conducted during the course of their admission onto a database for analysis.

Measure: To record the results of each patient's measured medical observations, clinical investigations and outcomes during the course of their admission.

Time: within 3 months

Description: Research staff will record data collected from eligible patients' electronic medical records from routine blood tests, chest x-rays, echos and any other associated clinical investigations conducted during the course of their admission onto a database and conduct comprehensive analysis.

Measure: To conduct retrospective analysis of data collected to map each patient's clinical journey during their admission

Time: within 3 months of data collection
62 Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS)

To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 22. Respiratory failure is defined as non-invasive ventilation or high-flow oxygen, intubation and mechanical ventilation, or ventilation with additional organ support (e.g., pressors, RRT, ECMO).

NCT04388826
Conditions
  1. Respiratory Distress Syndrome, Adult
Interventions
  1. Drug: Veru-111
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 29. Respiratory failure is defined as endotracheal intubation and mechanical ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, noninvasive positive pressure ventilation, clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision making is driven solely by resource limitation

Measure: Proportion of subjects that are alive without respiratory failure at Day 29.

Time: Day 29

Secondary Outcomes

Description: Improvement on the WHO Ordinal Scale for Clinical Improvement (8-point ordinal scale)

Measure: WHO clinical Improvement

Time: Day15 Day 22 and Day 29

Description: Proportion of subjects with normalization of fever and oxygen saturation through

Measure: Normalization of Fever and Oxygen

Time: Day 15, Day 22, and Day 29

Description: Percentage of subjects discharged from hospital

Measure: Discharge from Hospital

Time: Day 15 and Day 22

Description: Proportion of patients alive and free of respiratory failure

Measure: Patients alive and free of respiratory failure

Time: Day 15, and Day 22
63 A Prospective, Double-blind, Randomized, Parallel, Placebo-controlled Pilot Clinical Trial for the Evaluation of the Efficacy and Safety of Two Doses of WJ-MSC in Patients With Acute Respiratory Distress Syndrome Secondary to Infection by COVID-19

Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.

NCT04390139
Conditions
  1. COVID-19
  2. SARS-CoV 2
  3. Adult Respiratory Distress Syndrome
Interventions
  1. Drug: XCEL-UMC-BETA
  2. Other: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respi Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of patients who died, by treatment group

Measure: All-cause mortality at day 28

Time: Day 28

Secondary Outcomes

Description: Number of patients with treatment-emergent adverse events, by treatment group

Measure: Safety of WJ-MSC

Time: Day 28

Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group

Measure: Need for treatment with rescue medication

Time: Day 28

Description: Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group

Measure: Need and duration of mechanical ventilation

Time: Day 28

Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.

Measure: Ventilator free days

Time: Day 28

Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.

Measure: Evolution of PaO2 / FiO2 ratio

Time: Day 28

Description: Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group.

Measure: Evolution of the SOFA index

Time: Day 28

Description: Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group.

Measure: Evolution of the APACHE II score

Time: Day 28

Description: Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.

Measure: Duration of hospitalization

Time: Day 28

Description: Variation in the count and percentage of leukocytes and neutrophils, by treatment group.

Measure: Evolution of markers of immune response (leucocyte count, neutrophils)

Time: Day 28

Description: Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date

Measure: Feasibility of WJ-MSC administration

Time: Day 28

Description: Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment.

Measure: Feasibility of WJ-MSC administration

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR)

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH)

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: D-dimer

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: Ferritin

Time: Day 28

Other Outcomes

Description: Blood sample analysis

Measure: Analysis of subpopulations of lymphocytes and immunoglobulins

Time: Day 28

Description: In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)

Measure: Evaluation of the in vitro response of the receptor lymphocytes

Time: Day 28

Description: Reactivity will be assessed using ELISPOT

Measure: Study of reactivity against SARS-CoV-2 peptides

Time: Day 28

Description: Blood sample analysis

Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides

Time: Day 28

Description: Blood sample analysis for the patient's genomic sequencing

Measure: Genetic variability of patient's genotype in response to treatment

Time: Day 28

Description: Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample

Measure: Genetic variability of the SARS-CoV-2 genotype in response to treatment

Time: Day 28
64 Safety and Efficacy of Intravenous Infusion of Wharton's Jelly Derived Mesenchymal Stem Cell Plus Standard Therapy for the Treatment of Patients With Acute Respiratory Distress Syndrome Diagnosis Due to COVID 19: A Randomized Controlled Trial

Recent COVID 19 pandemic has overwhelmed health services all around the world, and humanity has yet to find a cure or a vaccine for the treatment of patients, mainly the severe ones, who pose a therapeutic challenge to healthcare professionals given the paucity of information we have regarding SARS-CoV-2 pathogenesis. Recently, reports mainly from China from patients treated with mesenchymal stem cells have shown promise in accelerating recovery, even in the critically ill and the therapy has sustained an increase in research because of it's powerful immunomodulatory effects, making it and interesting alternative in patients with lung and systemic inflammation. These effects could help treat a lot of patients and improve their outcomes, reason why phase I/II studies are needed to show their safety and experimental efficacy.

NCT04390152
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Wharton's jelly derived Mesenchymal stem cells.
  2. Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Evaluation of efficacy of WJ-MSC defined by mortality at 28 days of application.

Measure: Intergroup mortality difference with treatment

Time: 28 days.

Secondary Outcomes

Description: Safety evaluation of WJ-MSC describing and comparing incidence, type and severity of adverse events in both groups.

Measure: Number of patients with treatment related adverse events

Time: 6 months.

Description: Evaluation of the effect of WJ-MSC in the time of mechanical ventilation compared between the two groups, as prolonged mechanical ventilation days are associated with higher complication risks as pneumonia, tracheostomy and death.

Measure: Difference in days of mechanical ventilation between groups

Time: From ICU admission to 180 days.

Description: Evaluation of the effect of WJ-MSC in the time of hospitalization between the two groups as a measure of efficacy.

Measure: Median reduction of days of hospitalization

Time: From hospital admission to 180 days.

Description: Evaluation of the effect of WJ-MSC in the time of oxygen needs compared between the two groups as a measure of efficacy.

Measure: Median reduction of days of oxygen needs

Time: From hospital admission to 180 days.

Description: "Sequential Organ Failure Assessment" (SOFA) score is a tool used to determine the beginning and evolution of multiorgan failure, ranging from 0 to 24, being 24 the worst scenario. It has been proven useful as an outcome predictor of mortality and ICU stay. The result is the addition of the evaluation of each organ or system. Effect of WJ-MSC in the SOFA score will be compared between the two groups.

Measure: Difference between "Sequential Organ Failure Assessment" score between groups

Time: Baseline to 7 days

Description: Murray score is a tool used to classify lung injury. 0 = no lung injury, 0.1-2.5, mild to moderate lund injury, >2.5 Acute respiratory distress syndrome. The effect of WJ-MSC in the Murray score will be compared between the two groups.

Measure: Difference between median Murray score between groups

Time: Baseline and 7 days

Description: APACHE II is a prognostic score based on 12 different items obtained in the first 24 hours of ICU admission. Its mainly used as a single measure, but some authors have used and described prediction usefulness with repeated measures. It ranges from 0 to 71 points. Higher scores are related to higher ICU mortality. The effect of WJ-MSC in the APACHE II score will compared between the two groups.

Measure: Difference in APACHE II score between groups

Time: Baseline and 7 days

Description: Evaluation of the effect of WJ-MSC in lymphocyte count measured in absolute number/mm3. These laboratory measures have been associated with COVID 19 severity.

Measure: Difference in lymphocyte count between groups

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in C reactive protein concentration between the two groups, measured in mg/dl. Highest levels have been associated with COVID 19 severity and inflammation.

Measure: Changes in C reactive protein concentration between groups

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in D dimer between the two groups, measured in micrograms Highest levels have been associated with COVID 19 severity and thromboembolic complications.

Measure: Changes in D dimer concentration

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in ferritin compared between the two groups, measured in nanograms/ml. These laboratory measures have been associated with COVID 19 infection and severity.

Measure: Changes in ferritin concentration

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in LDH compared between the two groups, measured in units/liter. These laboratory measures have been associated with COVID 19 infection and severity.

Measure: Changes in lactate dehydrogenase concentration

Time: baseline and 21 days or discharge

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation.The effect of WJ-MSC in IL-6 will be compared between the two groups. It will be measured in picograms/ml.

Measure: Impact on interleukin 6 concentrations between groups.

Time: Baseline and 7 days

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 8 will be compared between the two groups. It will be measured in picograms/ml.

Measure: Impact on interleukin 8 concentrations between groups.

Time: Baseline and 7 days

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 10 will be compared between the two groups. It will be measured in picograms/ml.

Measure: Impact on interleukin 10 concentrations between groups.

Time: Baseline and 7 days

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in TNF alpha will be compared between the two groups. It will be measured in nanograms/ml.

Measure: Impact on tumor necrosis factor alpha concentrations between groups.

Time: Baseline to 7 days.

Other Outcomes

Description: Evaluation of the effect of WJ-MSC in pulmonary function measured with 6 minute walk. 6 minute walk is a test that gives information about pulmonary, cardiovascular and musculoskeletal functions. It measures the distance walked in 6 minutes in meters.

Measure: Changes in 6 minute walk between groups

Time: 6 months

Description: Evaluation of the effect of WJ-MSC in pulmonary function with thoracic CT scan. CT scan gives information about lung parenchyma, showing acute and chronic changes related to the underlying condition. Radiologic findings will be compared mainly comparing percentage of patients with pulmonary fibrosis.

Measure: Changes in Pulmonary Computed Tomography Scan between groups

Time: 6 months

Description: Evaluation of the effect of WJ-MSC in pulmonary function measured with spirometry, compared between the two groups. Spirometry gives information about lung volume and mobilization of air. Main parameters to be measured in spirometry are Forced Vital Capacity, Forced Expiratory Volume in 1 second and relation between these two to define if there is obstruction or restriction of airflow.

Measure: Changes in Spirometry between groups

Time: 6 months

Description: Evaluation of the effect of WJ-MSC in health related quality of life assessed by 36 Item Short Survey (SF-36). SF 36 is a patient reported tool. Each question is rated from 0 to 100, being 100 the best score possible. The scores are then compared to a population defined median score. Differences in global and specific scoring will be measured between groups.

Measure: Changes in health related quality of life between groups

Time: 6 months
65 Early Care, Therapeutic Education, and Psychological Intervention for the Management of Post-intensive Care Syndrome and Chronic Pain After Coronavirus Disease 2019 Infection. Simple-blind, Controlled, Randomized Trial.

COVID-19 (coronavirus 2019) disease has led to a large number of hospital admissions, many of which require admission to intensive care (ICU). Post-intensive care syndrome (PICS) is defined as deterioration or worsening of previous deterioration in the mental, physical or cognitive status that appears as a consequence of a critical illness and which persists after acute hospital care. Also, there is evidence that patients who survive a critical illness have a high prevalence of moderate to extreme chronic pain. Patients with COVID-19 disease are an especially susceptible population to develop PICS due to acute respiratory distress syndrome (ARDS) survivors have significant long-term deterioration in mental, cognitive, and functional health. This study hypothesis is that a specific care program based on early therapeutic education and psychological intervention improves the quality of life of patients at risk of developing PICS and chronic pain after COVID-19 disease.

NCT04394169
Conditions
  1. Post ICU Syndrome
  2. Chronic Pain
  3. Covid-19
Interventions
  1. Behavioral: Intervention program
MeSH:Syndrome Chronic Pain
HPO:Chronic pain

Primary Outcomes

Description: Health-related quality of life reported by the patient assessed through the visual analogue scale of the EQoL 5D/5L questionnaire at six months after discharge. [European quality of life 5 dimensions/5 levels ; from 0 (the worst imaginable health) to 100 (the best imaginable health) ]

Measure: Impact of intervention program on health-related quality of life (VAS)

Time: Six months after discharge

Secondary Outcomes

Description: Health-related quality of life reported by the patient assessed through the visual analogue scale of the EQoL 5D / 5L questionnaire at three months after discharge. [European quality of life 5 dimensions/5 levels ; from 0 (the worst imaginable health) to 100 (the best imaginable health)]

Measure: Impact of intervention program on health-related quality of life (VAS)

Time: Three months after discharge.

Description: Health-related quality of life reported by the patient assessed through health index of the EQoL 5D/5L questionnaire at three months after discharge. [European quality of life 5 dimensions/5 levels ; the questionnaire assesses quality of life in study participants according to 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each scored according to a scale of 1 (no problems) to 5 (indicating extreme problems) and generating a 5-digit code corresponding to quality of life]

Measure: Impact of intervention program on health-related quality of life (Index)

Time: Three months after discharge

Description: Health-related quality of life reported by the patient assessed through health index of the EQoL 5D/5L questionnaire at six months after discharge. [European quality of life 5 dimensions/5 levels ; the questionnaire assesses quality of life in study participants according to 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each scored according to a scale of 1 (no problems) to 5 (indicating extreme problems) and generating a 5-digit code corresponding to quality of life]

Measure: Impact of intervention program on health-related quality of life (Index)

Time: Six months after discharge

Description: Chronic pain intensity defined by BPI questionnaire (short version), at three and six months after discharge. [Brief pain inventory; A multidimensional questionnaire that evaluates pain intensity in the last 24 hours (worst, lowest, average) and current (right now). The questions are rated on a scale of 0 to 10, with 10 being the worst possible value. Subsequently, the average intensity score (BPI intensity score) is calculated.]

Measure: Impact of intervention program on chronic pain (intensity)

Time: Three and six months after discharge.

Description: Limitation of daily activities due to chronic pain, defined by BPI (short version), at three and six months after discharge. [Brief pain inventory; Multidimensional questionnaire that assesses the impact of pain on daily activities (general activity, encouragement, work, relationships with other people, sleep, enjoying life and the ability to walk). The questions are rated on a scale of 0 to 10, with 10 being the worst possible value. Subsequently, the mean score of the responses related to pain interference in activities (BPI interference score) is calculated.]

Measure: Impact of intervention program on chronic pain (limitation of daily activities)

Time: Three and six months after discharge.

Description: Pain catastrophization assessed by Pain Catastrophizing Scale at three and six months after hospital discharge. [Pain Catastrophizing Scale; Consisting of 13 questions that explore the frequency of thoughts and feelings that the interviewees have in the presence of current or anticipated pain, which are grouped into three scoring subscales (magnification, rumination and defenselessness). Each question is rated on a 5-point scale (0: not at all; 4: all the time). Being the maximum total score of 52 points.]

Measure: Impact of intervention program on chronic pain (Pain catastrophization)

Time: Three and six months after discharge.

Description: Clinically significant anxiety or depression symptoms prevalence at three and six months, assessed by the HAD test. [hospital anxiety and depression test; 14 questions, with two subscales, one for anxiety and the other for depression, with seven items each, the maximum score is 21 for each subscale. The cut-off points from zero to seven imply the absence of clinically relevant anxiety and depression, from eight to ten symptoms that require consideration and from 11 to 21 reports the presence of relevant symptoms, with a very probable diagnosis of anxiety or depression.]

Measure: Impact of intervention program on anxiety or depression incidence

Time: Three and six months after discharge.

Description: Probable post-traumatic stress syndrome prevalence at three and six months after discharge assessed by the DSM ( Diagnostic and Statistical Manual of Mental Disorders) V PTSD Checklist questionnaire (PCL-5) [PTSD Checklist questionnaire; It contains 20 questions that correspond to the DSM V PTSD (Post Traumatic Stress Disorder) criteria. Participants rated their symptoms on a scale of 0 (not at all), 1 (slightly), 2 (moderately), 3 (quite) to 4 (extremely), with a score ranging from 0 to 80. A total of the severity of the symptoms can be made, adding the score of each question (interval 0-80). The severity of each symptom can be evaluated, adding the score of the questions. The cut-off point to use for a provisional diagnosis of PTSD is 31 points.]

Measure: Impact of intervention on probable post-traumatic stress syndrome incidence

Time: Three and six months after discharge.
66 Randomized-controlled Trial of HFNC Alone vs HFNC and Awake Self-proning for Treatment of Severe COVID-19

Prone positioning is an established intervention in mechanically ventilated acute respiratory distress syndrome (ARDS) patients, with demonstrated reductions in mortality. Preliminary data suggest that awake proning in patients with COVID-19 treated with high-flow nasal oxygenation (HFNO) improves gas exchanges, and might be associated with a reduced need of mechanical ventilation, and reduced mortality. Further investigation in a formal randomized-controlled trial is need.

NCT04395144
Conditions
  1. Coron
  2. Coronavirus Infection
  3. COVID
  4. Severe Acute Respiratory Syndrome
  5. Respiratory Failure
  6. Respiratory Insufficiency
  7. Respiratory Distress Syndrome
  8. ARDS
  9. Lung Diseases
Interventions
  1. Procedure: Awake Prone Positioning
  2. Procedure: Standard care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Lung Diseases Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Pulmonary Valve Insufficiency Syndrome
HPO:Abnormal lung morphology Pulmonary insufficiency

Primary Outcomes

Measure: Rate of Therapeutic failure, defined as a combined outcome of rate of intubation or death

Time: Up to 28 days after randomization

Secondary Outcomes

Measure: Intubation rate

Time: Up to 28 days after randomization

Measure: Mortality

Time: Up to 28 days after randomization

Measure: Days spent on mechanical ventilation

Time: Until discharge, up to 24 weeks after randomization

Measure: Days spent in the ICU

Time: Until discharge, up to 24 weeks after randomization

Measure: Hospital stay (in days)

Time: From admission to discharge, up to 24 weeks after randomization

Other Outcomes

Description: Total time spent in prone position, as recorded by nursing or respiratory therapists

Measure: Time in prone position

Time: Up to 28 days post randomization

Description: Daily evolution of oxygenation

Measure: Oxygenation (SpO2/FiO2 ratio)

Time: Until HFNC weaning, or up to 14 days after randomization, whichever is first
67 A Phase 2 Clinical Trial to Assess the Safety and Efficacy of Complement 3 Inhibitor, AMY-101, in Patients With Acute Respiratory Distress Syndrome Due to COVID-19 (SAVE)

The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of AMY-101, a potent C3 inhibitor, for the management of patients with ARDS caused by SARS-CoV-2 infection. We will assess the efficacy and safety, as well as pharmacokinetics (PK), and pharmacodynamics (PD). The study will assess the impact of AMY-101 in patients with severe COVID19; specifically, it will assess the impact of AMY-101 1) on survival without ARDS and without oxygen requirement at day 21 and 2) on the clinical status of the patients at day 21.

NCT04395456
Conditions
  1. Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)
Interventions
  1. Drug: AMY-101
  2. Other: WFI 5% glucose
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: The proportion of patients who are alive, without evidence of ARDS (i.e. PaO2/FIO2 >300 mm Hg), who do not require any oxygen support (in room air).

Time: 21 days

Description: The clinical status is based on the following six-category ordinal scale: 1: not hospitalised; 2: hospitalised, not requiring supplemental oxygen; 3: hospitalised, requiring supplemental oxygen; 4: hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 5: hospitalised, requiring ECMO, invasive mechanical ventilation, or both; and 6: death.

Measure: The proportion of patients assigned to each category, of a six-category ordinal scale.

Time: 21 days

Secondary Outcomes

Description: The clinical status is based on the following six-category ordinal scale: 1: not hospitalised; 2: hospitalised, not requiring supplemental oxygen; 3: hospitalised, requiring supplemental oxygen; 4: hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 5: hospitalised, requiring ECMO, invasive mechanical ventilation, or both; and 6: death.

Measure: The proportion of patients assigned to each category, of a six-category ordinal scale.

Time: On days 7, 14, and 44

Measure: Proportion of patients surviving

Time: Through to day 44

Description: With respiratory failure defined as any of the following: Worsening of severe gas transfer deficit, accounting for a shift in ARDS disease category (PaO2/FiO2 ≤200 for patients with PaO2/FiO2 >200 at baseline; PaO2/FiO2 ≤100 for patients with PaO2/FiO2 >100 at baseline), Persistent respiratory distress while receiving oxygen (persistent marked dyspnea,use of accessory respiratory muscles, paradoxical respiratory movements), Transfer to the intensive care unit for intubation, Death.

Measure: Proportion of respiratory failure-free survival

Time: Day 44

Measure: Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air)

Time: Through day 44

Measure: Cumulative incidence of freedom from oxygen requirement

Time: Through day 44

Measure: Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS

Time: Within 14 days after inclusion in the study

Measure: Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS

Time: Within 14 days after inclusion in the study

Measure: Proportion of patients developing thrombotic microangiopathies

Time: Through day 44

Measure: Changes in PaO2 and PaO2/FIO2

Time: Through day 44

Measure: Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS)

Time: Through day 44

Measure: Changes in maximal and minimal cardiovascular parameters: Respiratory rate

Time: Through day 44

Measure: Changes in maximal and minimal cardiovascular parameters: Heart Rate

Time: Through day 44

Measure: Changes in levels of biomarkers of inflammation (CBC, CRP, Ferritin, Procalcitonin, D-dimers, LDH)

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Length of stay in ICU

Time: Through day 44

Measure: Cumulative incidence of discharge from hospital

Time: Through day 44

Measure: Number of adverse events

Time: Through day 44

Measure: Changes in levels of anti-drug antibodies

Time: On day 0 , 14 and 44

Measure: Changes in levels of biomarkers of complement activity: C3, C3a, C5a, sC5b-9

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Changes in levels of biomarkers of cytokine release syndrome: IL-1, IL-6, IL-12

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Changes in levels of Club Cell protein CC16 (biomarker of lung damage )

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Changes in levels of AMY-101 plasma level

Time: On days 1, 2, 4, 7, 10, 14, 15, 21
68 Cellular Immuno-Therapy for COVID-19 ARDS (CIRCA-19) the Vanguard Study

The clinical picture of the novel corona virus 2 (SARS-CoV-2) disease (COVID-19) is rapidly evolving. Although infections may be mild, up to 25% of all patients admitted to hospital require admission to the intensive care unit, and as many as 40% will progress to develop severe problems breathing due to the acute respiratory distress syndrome (ARDS). ARDS often requires mechanical ventilation, with a 50% risk of mortality. Researchers at the Ottawa Hospital Research Institute (OHRI) have been studying the potential therapeutic role of mesenchymal stromal/stem cells, or MSCs, for the treatment of ARDS for over a decade. This has led to the world's first clinical trial using MSC therapy for patients with severe infections (sepsis) which is often associated with ARDS (NCT02421484). This trial demonstrated tolerability, and potential signs of efficacy. In addition, the investigators have established expertise in producing clinical-grade MSCs and have received approval from Health Canada for the use of MSCs in three different clinical studies. The investigators propose a Phase 1, open label, dose-escalating and safety trial using a 3+3+3 design to determine the safety, and maximum feasible tolerated dose of repeated delivery of Bone Marrow (BM)-MSCs intravenously. This will take advantage of a limited supply of screened BM-MSCs lines which are available now in the GMP facility and will allow to have product ready to deliver to the first patient within weeks. The investigators will enroll up to 9 patients; each receiving repeated unit doses of BM-MSCs delivered by IV infusion on each of 3 consecutive days (24±4 hours apart) according to the following dose-escalation schedule (3 patients per dose panel): (i) Panel 1: 25 million cells/unit dose (cumulative dose: 75 million MSCs), (ii) Panel 2: 50 million cells/unit dose (cumulative dose: 150 million MSCs), (iii) Panel 3: up to 90 million cells/unit dose (cumulative dose: up to 270 million MSCs).

NCT04400032
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Covid19
Interventions
  1. Biological: Mesenchymal Stromal Cells
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 to determine the maximum feasible tolerated dose (MFTD) of BM-MSCs given to patients with COVID-19

Measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

Time: At time of infusion until one year post-infusion

Secondary Outcomes

Description: Number of Participants alive by Day 28

Measure: Number of Participants alive by Day 28

Time: Day 28

Description: Number of Participants with ventilator-free Days by Day 28

Measure: Number of Participants with ventilator-free Days by Day 28

Time: Day 28
69 A Randomized, Double-Blinded, Vehicle-Controlled, Multicenter, Parallel-Group Study of APL-9 in Mild to Moderate Acute Respiratory Distress Syndrome Due to COVID-19

The purpose of this study is to evaluate the safety and effectiveness of APL-9 in adults with mild to moderate ARDS (acute respiratory distress syndrome) caused by COVID-19 who are hospitalized and require supplemental oxygen therapy with or without mechanical ventilation. It is thought that COVID-19 activates the complement system, part of the immune system that responds to infection or tissue damage, and increases inflammation in the lungs. APL-9 has been designed to inhibit or block activation of part of the complement pathway, and potentially reduce inflammation in the lungs. Part 1 of the study is open-label to evaluate safety; all participants will receive APL-9 plus standard of care. Part 2 of the study is double-blind, randomized; participants will receive either APL-9 or the vehicle-control plus standard of care.

NCT04402060
Conditions
  1. COVID
  2. Covid-19
  3. Coronavirus
  4. Coronavirus Infection
  5. Severe Acute Respiratory Syndrome
  6. Severe Acute Respiratory Syndrome Coronavirus 2
  7. Sars-CoV2
  8. Ards
  9. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: APL-9
  2. Other: Vehicle Control
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: Cumulative incidence of treatment-emergent serious adverse events and treatment-emergent adverse events.

Time: Day 1 through Day 21

Secondary Outcomes

Measure: Hospital length of stay

Time: Day 1 through Day 21

Measure: Any cause of mortality

Time: Day 1 through day 51

Description: The minimum value is 0 and maximum value is 24. The higher a score the worse the outcome.

Measure: Sequential Organ Failure Assessment

Time: Day 1 through day 21

Measure: Total duration of mechanical ventilation

Time: Day 1 through day 21

Measure: Total duration of oxygen therapy

Time: Day 1 through day 21
70 Stellate Ganglion Block (SGB) for COVID-19 Acute Respiratory Distress Syndrome (ARDS)

The purpose of this study is to understand if it is safe and useful to perform SGB (Stellate Ganglion Block) in patients who have severe lung injury Acute Respiratory Distress Syndrome (ARDS) due to COVID-19 infection.

NCT04402840
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Procedure: Stellate Ganglion Block
MeSH:Ganglion Cysts Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Adverse events that can atleast unlikely be attributed to SGB

Measure: Adverse events related to SGB

Time: 3 Months

Description: All adverse events related to COVID-19

Measure: All Adverse events

Time: 3 Months

Description: Death due to any cause

Measure: Death

Time: 3 Months

Secondary Outcomes

Description: Change from baseline (descibed as last ratio prior to procedure)

Measure: PaO2/FiO2 or SpO2/FiO2(SF) ratio change from baseline

Time: 3 Months

Description: change from last imaging data obtained prior to SGB procedure

Measure: Radiographic criteria

Time: 3 Months

Measure: Incidence of cardiac arrhythmia

Time: 3 Months

Measure: Resolution of cardiac arrhythmia

Time: 3 Months

Measure: Cardiac function

Time: 3 Months

Measure: Clinical relevant Laboratory testing (d-dimer, Ferritin, Troponin T, LDH)

Time: 3 Months
71 A Prospective Randomized Trial of Prone Positioning Versus Usual Care for Patients With Do-not-intubate Goals of Care and Hypoxemic Respiratory Failure During the Coronavirus SARS-CoV-2 (COVID-19) Pandemic

The purpose of this trial is to determine whether Prone Positioning (PP) improves outcomes for non-intubated hospitalized patients with hypoxemic respiratory failure due to COVID-19, who are not candidates for mechanical ventilation in the ICU. The investigators hypothesize that PP will reduce in-hospital mortality or discharge to hospice, compared with usual care for non-intubated patients with do-not-intubate goals of care with hypoxemic respiratory failure due to probable COVID-19.

NCT04402879
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
  2. COVID-19
  3. Acute Respiratory Distress Syndrome
  4. ARDS
  5. Hypoxemic Respiratory Failure
Interventions
  1. Procedure: Prone Positioning (PP)
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome

Primary Outcomes

Description: In-hospital mortality or discharge to hospice at Day 60.

Measure: Hospital mortality or discharge to hospice

Time: 60 days

Secondary Outcomes

Description: An Adverse Event (AE) is any unfavourable or other finding (including clinically significant laboratory tests), symptom or disease occurring during the during of the study, whether or not it is considered to be related to the medicinal (investigational) product, not explicitly classified elsewhere in this protocol, and whether or not it is expected. A Serious Adverse Event (AE) is any unfavourable medical finding (including clinically significant laboratory tests) at any dose that: Results in death (primary outcome) Is life threatening Results in persistent of significant disability or incapacity Requires in in-patient hospitalisation or prolongation of Hospitalisation

Measure: Adverse Events and Serious Adverse Events

Time: 60 days

Description: Change in SpO2 during each PP session (SpO2 in prone position - SpO2 prior to prone positioning). Clinicians will be asked to record this change for the first proning session per shift (for 12 hour shifts this will result in 2 proning sessions being documented per 24 hour period, and for 8 hour shifts this will result in 3 proning sessions being documented per 24 hour period).

Measure: Change in SpO2

Time: 60 days

Description: Number of hospital free days in the 60 days after enrolment.

Measure: Hospital free days

Time: 60 days

Description: Admission to the Intensive Care Unit.

Measure: Admission to ICU

Time: 60 days

Description: Patient is intubated and requires mechanical ventilation.

Measure: Intubation and mechanical ventilation

Time: 60 days

Description: Patient requires non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).

Measure: Initiation of non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).

Time: 60 days

Description: The number of oxygen-free days at Day 60 (censored at discharge).

Measure: Oxygen-free days

Time: 60 days

Description: Time from admission to all-cause in-hospital death.

Measure: In-hospital death (time)

Time: 60 days

Description: Death at 90 days.

Measure: Death at 90 days

Time: 90 days
72 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome (ARDS) and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)

To evaluate the proportion of subjects alive and free of respiratory failure (e.g. need for non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the need for continued renal replacement therapy (RRT) on Day 28. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 <10 mL/min/1.73 m2.

NCT04402957
Conditions
  1. COVID
  2. Severe Acute Respiratory Syndrome
  3. Sars-CoV2
  4. Acute Kidney Injury
Interventions
  1. Drug: LSALT peptide
  2. Drug: Placebo
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Acute Kidney Injury Syndrome Wounds and Injuries
HPO:Acute kidney injury

Primary Outcomes

Description: To evaluate the efficacy of intravenous LSALT peptide plus standard of care to prevent the progression of COVID-19 to mild, moderate or severe ARDS, acute kidney injury, cardiomyopathy, acute liver injury, coagulopathy, or death in patients infected with SARS-CoV-2 compared with placebo plus standard of care.

Measure: Development of Acute Respiratory Distress Syndrome (ARDS) and Other Organ Injuries

Time: 28 days

Secondary Outcomes

Description: High-frequency oscillatory ventilation, with its rapid delivery of low tidal volumes and a respiratory rate in the range of 60 to 900 breaths/minute, has also been utilized in ARDS patients.

Measure: Ventilation-free days

Time: 28 days

Description: Oxygen therapy provided as non-invasive therapy for ARDS patients.

Measure: Time on nasal cannula or oxygen masks

Time: 28 days

Description: 28 day mortality - all cause and attributable

Measure: 28 day mortality - all cause and attributable

Time: 28 days

Description: ICU and hospitalization length of stay (days)

Measure: ICU and hospitalization length of stay (days)

Time: 28 days

Description: Swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication → virologic clearance rate

Measure: SARS-CoV2 testing

Time: 28 days

Description: Extracorporeal membrane oxygenation (ECMO) is often used for severe ARDS to allow lung healing/repair and reverse respiratory failure.

Measure: Need and duration for extracorporeal membrane oxygenation (ECMO)

Time: 28 days

Description: Vasopressor free days

Measure: Vasopressor free days

Time: 28 days

Description: Chest X-rays performed at Baseline, Day 3, at clinical improvement, and end-of-treatment (EOT) and study (EOS) to determine presence of bilateral opacities.

Measure: Radiographic pulmonary assessments

Time: 28 days

Description: Change in daily mMRC dyspnea and SOFA scores (0 to 4) with 4 being the most severe outcome

Measure: Change in modified Medical Research Council (mMRC) dyspnea and Sequential Organ Failure Assessment (SOFA) scores

Time: 28 days

Description: Incidence of other organ (non-lung) disorders

Measure: Incidence of non-lung disorders

Time: 28 days

Description: Change in liver function tests (ALT, AST, and total bilirubin levels) from baseline

Measure: Measures of liver dysfunction

Time: 28 days

Description: Change in SCr and eGFR from baseline

Measure: Measures of kidney dysfunction

Time: 28 days

Description: Change in highly-sensitive troponin (hs-troponin) from baseline

Measure: Measures of cardiac dysfunction

Time: 28 days

Description: Change from baseline ACT, aPTT, and/or PT/INR levels

Measure: Measures of coagulopathies

Time: 28 days

Description: Change in baseline antiviral immunoglobulins (IgG, IgM) at EOS.

Measure: Changes in immunogenic responses

Time: 28 days

Description: Changes in total healthcare costs from admission to discharge between treatment groups.

Measure: Healthcare outcomes

Time: 28 days

Description: Change in serum cytokines including IL-1α, IL-1ß, IL-1ra, IL-5, IL-6, IL-8, IL-12, TNFα, CXCL10/IP10, MCP-3, and ferritin drawn at the same time as LSALT peptide levels

Measure: Molecular changes in pro-inflammatory pathways

Time: 28 days

Description: Pharmacokinetics of LSALT peptide over the study period.

Measure: Pharmacokinetics of LSALT peptide

Time: 28 days
73 Efficacy and Safety of Angiotensin II Use in COVID-19 Patients With Acute Respiratory Distress Syndrome

This study aims to find out whether the use of angiotensin II, which is a drug to raise blood pressure has been approved by European Medical Agency in August 2019, as an add-on medication to increase blood pressure in patients with COVID-19, acute severe lung injury, inflammation and severe shock, compared with standard medication. In addition, the investigators will collect the data of Anakinra, another drug which is frequently used in this condition to reduce inflammation. The investigators will collect clinical data and outcomes from critical care patients. The investigators will analyse for whom these drugs are most beneficial and explore whether there are any patients who don't benefit or have side effects.

NCT04408326
Conditions
  1. COVID
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Angiotensin II
  2. Drug: Interleukin-1 receptor antagonist
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Percentage

Measure: Proportions of patients with mean arterial pressure ≥ 65 mmHg or an increase of mean arterial pressure ≥10 mmHg at 3 hours

Time: 3 hours

Secondary Outcomes

Description: microgram/kg/min

Measure: Noradrenaline dose

Time: 1 hour and 3 hours

Description: Changes in score, minimum 0, maximum 24, the higher score showing worse prognosis

Measure: Sequential Organ Failure Assessment (SOFA) score

Time: baseline, 24, and 48 hours

Description: Patients who are alive and do not require renal replacement therapy at 28 days

Measure: RRT-free days

Time: 28 days

Description: Proportions of patients who do not require renal replacement therapy

Measure: RRT discontinuation

Time: 7 and 28 days

Description: micromol/L

Measure: Serum creatinine

Time: 7 days and 28 days

Description: Changes in value

Measure: PaO2/FiO2 ratio

Time: baseline, 24, and 48 hours

Description: Mortality rate

Measure: Mortality

Time: 7 days and 28 days

Description: e.g. arrhythmia, thromboembolism, etc.

Measure: Adverse events

Time: 28 days

Description: Change in serum C-reactive protein

Measure: Change in serum C-reactive protein

Time: 7 days

Description: Change in serum ferritin

Measure: Change in serum ferritin

Time: 7 days
74 Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory Therapy in Patients Diagnosed With COVID-19 Disease

The aim of the study is to clinically use bovine Lf as a safe antiviral adjuvant for treatment and to assess the potential in reducing mortality and morbidity rates in COVID-19 patients. The study was approved by the ethical committee of the Egyptian Center for Research and Regenerative Medicine in 11-5-2020.

NCT04412395
Conditions
  1. Corona Virus Infection
  2. Middle East Respiratory Syndrome (MERS)
  3. Acute Respiratory Distress Syndrome
  4. Coronavirus Infection
  5. COVID-19
  6. SARS-CoV 2
Interventions
  1. Dietary Supplement: Lactoferrin (Apolactoferrin)
  2. Drug: Placebo of excipient(s) will be administered
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respira Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Comparing the influence of the intervention on the Survival rate.

Measure: Survival rate.

Time: up to 8 weeks.

Description: For mild/moderate symptoms patients: fever, cough and other symptoms relieved with improved lung CT - For severe symptoms patients: fever, cough and other symptoms relieved with improved lung CT, and oxygen saturation by pulse oximetry (SPO2 )> 93% for nonasthmatic patients, and from 88-92% in asthmatic patients.

Measure: Rate of disease remission.

Time: up to 4 weeks.

Description: Comparing the influence of the intervention on the PCR negative results.

Measure: The number of patients with PCR negative results.

Time: up to 4 weeks.

Secondary Outcomes

Description: Recording the changes from severe to moderate or mild and the time taken.

Measure: Mean change in the disease severity (clinical assessment).

Time: up to 4 weeks.

Description: Recording the changes in blood pressure mmHg.

Measure: Mean change in blood pressure.

Time: up to 4 weeks.

Description: Recording the changes in heart rate in beat/second.

Measure: Mean change in heart beats.

Time: up to 4 weeks.

Description: Recording the changes in body temperature in Celsius.

Measure: Mean change in body temperature.

Time: up to 4 weeks.

Description: Recording the changes in the respiratory rate in breath/minute.

Measure: Mean change in body respiratory rate.

Time: up to 4 weeks.

Description: Recording the changes in arterial oxygen saturation in mmHg.

Measure: Mean change in oxygen saturation.

Time: up to 4 weeks.

Description: Recording the changes in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).

Measure: Mean change in the ratio in arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).

Time: up to 4 weeks.

Description: Recording the changes in complete blood picture (CBC) in cells per liter.

Measure: Mean change in complete blood picture (CBC).

Time: up to 4 weeks.

Description: Recording the changes in C reactive protein (CRP) in mg/L.

Measure: Mean change in C reactive protein (CRP).

Time: up to 4 weeks.

Description: Recording the changes in erythrocyte sedimentation rate (ESR) in mm/hr.

Measure: Mean change in erythrocyte sedimentation rate (ESR).

Time: up to 4 weeks.

Description: Recording the changes in D-dimer in ng/mL.

Measure: Mean change in D-dimer.

Time: up to 4 weeks.

Description: Recording the changes in ferritin in ng/mL.

Measure: Mean change in ferritin.

Time: up to 4 weeks.

Description: Recording the changes in liver Albumin in g/L.

Measure: Mean change in liver Albumin.

Time: up to 4 weeks.

Description: Recording the changes in total and direct Bilirubin in mg/dL.

Measure: Mean change in total and direct Bilirubin.

Time: up to 4 weeks.

Description: Recording the changes in prothrombin time (PT), partial thromboplastin time (PTT ) in seconds and calculating International Normalized Ratio (INR).

Measure: Mean change in prothrombin time (PT) and partial thromboplastin time (PTT ).

Time: up to 4 weeks.

Description: Recording the changes in aspartate aminotransferase (AST) in IU/L.

Measure: Mean change in aspartate aminotransferase (AST).

Time: up to 4 weeks.

Description: Recording the changes in Alanine Aminotransferase (ALT) in IU/L.

Measure: Mean change in Alanine Aminotransferase (ALT).

Time: up to 4 weeks.

Description: Recording the changes in Blood Urea Nitrogen (BUN) in mg/dL.

Measure: Mean change in Blood Urea Nitrogen (BUN).

Time: up to 4 weeks.

Description: Recording the changes in Serum Creatinine in mg/dL.

Measure: Mean change in Serum Creatinine.

Time: up to 4 weeks.

Description: Recording the changes in Serum Creatinine in ml/min.

Measure: Mean change in Serum Creatinine clearance.

Time: up to 4 weeks.

Description: Recording the changes in Glomerular filtration rate (GFR ) ml/min/m2.

Measure: Mean change in Glomerular filtration rate (GFR ).

Time: up to 4 weeks.

Description: Recording the changes in interleukin-1 (IL-1) in pg/ml.

Measure: The mean change in serum interleukin-1 (IL-1).

Time: up to 4 weeks.

Description: Recording the changes in interleukin-6 (IL-6) in pg/ml.

Measure: The mean change in serum interleukin-6 (IL-6).

Time: up to 4 weeks.

Description: Recording the changes in interleukin-10 (IL-10) in pg/ml.

Measure: The mean change in serum interleukin-10 (IL-10).

Time: up to 4 weeks.

Description: Recording the changes in tumor necrosis factor-alpha (TNF alpha) in ng/ml.

Measure: The mean change in serum tumor necrosis factor-alpha (TNF alpha).

Time: up to 4 weeks.

Description: Recording the changes in immunoglobulin G (IgG) in ng/ml.

Measure: Mean changes in immunoglobulin G (IgG).

Time: up to 4 weeks.

Description: Recording the changes in immunoglobulin M (IgM) in ng/ml.

Measure: Mean changes in immunoglobulin M (IgM).

Time: up to 4 weeks.

Description: Recording the changes in PCR viral load in copies/mL.

Measure: The mean change in PCR viral load.

Time: up to 4 weeks.

Description: Recording the changes in lung CT.

Measure: Mean change in lung CT manifestation.

Time: up to 4 weeks.

Description: Recording any unexpected Adverse Events of the intervention.

Measure: Nature and severity of Adverse Events.

Time: up to 4 weeks.

Description: Recording the changes (the average time of lung imaging recovery), as assessed by lung CT.

Measure: Time for lung recovery.

Time: up to 8 weeks.

Description: Recording the changes the event of missed drug doses.

Measure: The number of missed drug doses among each treatment group.

Time: up to 4 weeks.
75 A Phase 1/2 Study of ALX148 in Combination With Azacitidine in Patients With Higher Risk Myelodysplastic Syndrome (MDS)

This Phase 1/2 clinical study will evaluate ALX148 in combination with azacitidine for the treatment of patients with higher risk myelodysplastic syndrome (MDS).

NCT04417517
Conditions
  1. Higher Risk Myelodysplastic Syndromes
Interventions
  1. Drug: ALX148
  2. Drug: Azacitidine
MeSH:Preleukemia Myelodysplastic Syndromes Syndrome
HPO:Myelodysplasia

Primary Outcomes

Description: Number of participants with a DLT

Measure: Phase 1: Dose Limiting Toxicities (DLT)

Time: Up to 28 days

Description: Number of participants achieving a response per International Working Group (IWG) criteria

Measure: Phase 2: Objective response rate (ORR)

Time: Approximately 6 months
76 Characterization and Management of Post Intensive Care Syndrome in COVID19 Patients.

This project is based in the implementation of a combined monitoring system (technological solutions and medical visits) in survivors of the critical illness due to the infectious disease by COVID-19. The main objective of the project is to characterize the Post-Intensive Care Syndrome (PICS) and detect early needs for specific treatment.

NCT04422444
Conditions
  1. COVID19
  2. Post Intensive Care Unit Syndrome
Interventions
  1. Diagnostic Test: Questionnaires
MeSH:Syndrome

Primary Outcomes

Description: Health related quality of live scale. Values are directly transformed in T scores (mean=50; SD=10), with higher scores meaning better outcome.

Measure: Change from baseline Short Form 12 Health Survey (SF12) at 12 month

Time: Every month during a 12 months follow-up period

Secondary Outcomes

Description: Measure of independent living skills. Values are from 0 to 8, with higher scores meaning better outcome.

Measure: Change from baseline Lawton & Brody Instrumental activities of daily living scale at 12 months

Time: Every month during a 12 months follow-up period

Description: Self-report measure of cognitive dysfunction. Values are from 0 to 22, with lower scores meaning better outcome.

Measure: Change from baseline Perceived Deficits Questionnaire (PDQ) at 12 months

Time: Every month during a 12 months follow-up period

Description: A self-assessment instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient. Values are from 0 to 42, with lower scores meaning better outcome.

Measure: Change from baseline Hospital Anxiety and Depression Scale (HADS) at 12 months

Time: Every month during a 12 months follow-up period

Description: Self-report measure of Post Traumatic Stress Disorder (PTSD) symptoms.

Measure: Change from baseline Davidson Trauma Scale (DTS) at 12 months

Time: Every month during a 12 months follow-up period. Values are from 0 to 136, with lower scores meaning better outcome.
77 A Randomized, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of Once Weekly Subcutaneous Injections of PB1046, a Sustained-Release VIP (Vasoactive Intestinal Peptide) ANalogue, in Hospitalized COVID-19 Patients at HiGh Risk for Rapid Clinical Deterioration and ARDS (PB1046 VANGARD Study)

This is a multicenter, randomized, double-blind, parallel group study to investigate the efficacy of PB1046 by improving the clinical outcomes and increasing days alive and free of respiratory failure in hospitalized COVID-19 patients at high risk for rapid clinical deterioration, acute respiratory distress syndrome (ARDS) and death. The study will enroll approximately 210 hospitalized COVID-19 patients who require urgent decision-making and treatment at approximately 20 centers in the United States.

NCT04433546
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Coronavirus
  3. Hypoxic Respiratory Failure
  4. Hypoxemic Respiratory Failure
  5. Respiratory Complication
  6. Respiratory Insufficiency
  7. Cardiac Dysfunction
  8. Pneumonia
  9. Pulmonary Edema
  10. Pulmonary Inflammation
  11. Respiratory Failure
  12. Cytokine Storm
  13. COVID 19
  14. SARS-CoV-2
  15. Cardiac Event
  16. Cardiac Complication
  17. Cardiac Failure
  18. Cardiac Infarct
Interventions
  1. Drug: PB1046
  2. Drug: Low Dose (10 mg) Control
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Pulmonary Edema Pulmona Pulmonary Valve Insufficiency Heart Failure Syndrome Inflammation Clinical Deterioration
HPO:Congestive heart failure Left ventricular dysfunction Pneumonia Pulmonary edema Pulmonary insufficiency Right ventricular failure

Primary Outcomes

Measure: Days alive and free of respiratory failure from initiation of PB1046

Time: 28 days

Secondary Outcomes

Measure: Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge)

Time: 28 days

Description: PaO2:FiO2 ratio is the ratio of partial pressure of arterial oxygen to percentage of inspired oxygen

Measure: Development of ARDS (PaO2:FiO2 ratio < 300 mm Hg) during hospitalization

Time: Any time point between injection initiation and Day 28

Measure: All-cause mortality

Time: 28 days

Description: Composite of: Total hospital days, Total ICU days, Total days of ventilator use, Total days of ECMO, Total days of invasive hemodynamic monitoring, Total days of mechanical circulatory support, Total days of inotropic or vasopressor therapy

Measure: Reduction in hospital resource utilization defined as a composite of:total days: in hospital, in ICU, on ventilator, on ECMO, with invasive hemodynamic monitoring, with mechanical circulatory support, and with inotropic or vasopressor therapy

Time: 28 days

Measure: Time to clinical improvement as defined by reduction of at least 2 points on an 8-category ordinal scale of clinical improvement or discharge from hospital, whichever comes first.

Time: Any time point between injection initiation and Day 28

Measure: Change from baseline in cardiac marker high sensitivity troponin I (hsTnI)

Time: Any time point between injection initiation and Day 35+7

Measure: Change from baseline in cardiac marker NT-proBNP

Time: Any time point between injection initiation and Day 35+7

Measure: Change from baseline in TNF alpha

Time: Any time point between injection initiation and Day 35+7

Measure: Change from baseline in IL-1

Time: Any time point between injection initiation and Day 35+7

Measure: Change from baseline in IL-6

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by clinical adverse events (AEs) and their relationship to PB1046

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by vital signs and their relationship to PB1046

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by laboratory results and their relationship to PB1046

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by electrocardiogram (ECG) abnormalities and their relationship to PB1046

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by incidence of anti-drug antibodies and their relationship to PB1046

Time: Any time point between injection initiation and Day 35+7

Other Outcomes

Measure: Impact on invasive hemodynamic parameters as measured by pulmonary artery pressure if patients require right-heart catherization

Time: Any time point between injection initiation and Day 35+7

Measure: Impact on invasive hemodynamic parameters as measured by cardiac output if patients require right-heart catherization

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence of multi-system organ failure (MSOF)

Time: Any time point between injection initiation and Day 35+7

Measure: Number of multi-system organ failure (MSOF) free days

Time: Any time point between injection initiation and Day 35+7

Measure: Number of subjects requiring extracorporeal membrane oxygenation (ECMO)

Time: Any time point between injection initiation and Day 35+7
78 Physical Rehabilitation in Intensive Care Unit in Acute Respiratory Distress Syndrome Patients With COVID-19

The primary aim of this study is to evaluate the effect of physical rehabilitation performed in intensive care unit on the range of joint motions and muscle strength of survivors following discharge from intensive care unit in patients with COVID-19. Secondary outcome is to assess the duration of mechanical ventilation, length of stay in intensive care unit and in hospital, and mortality rates during intensive care unit stay and health related quality of life following discharge in survivors. Until April 14 patients were provided all the intensive care managements except for rehabilitation and patients discharged before this time constituted the 'non-rehabilitation' group (n=17). Patients discharged after April 14 were provided rehabilitation in addition to usual intensive care unit care and constituted the study 'rehabilitation' group (n=18). Passive range of motion exercises to each joint and neuromuscular electrical stimulation to bilateral quadriceps and tibialis anterior muscles were applied 6 days/week in the 'rehabilitation' group during intensive care unit stay.

NCT04435080
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Rehabilitation
  4. Intensive Care Unit Acquired Weakness
  5. Critical Illness Polyneuromyopathy
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome Critical I Critical Illness

Primary Outcomes

Description: Hand grip strength is an indicator of overall muscle strength that predicts mortality in older patients. Handgrip strength was measured using a handheld dynamometer according to the instructions of the American Society of Hand Therapists.Patients were seated placing their arms by their sides with the elbow flexed to 90°, the forearm mid-prone, and the wrist in neutral position. Patients were asked to grip the dynamometer with maximal effort using standard verbal encouragement. Three trials were performed in the dominant hand with a 30 sec rest between trials and the highest value was recorded in kg. The cut-off values of grip strength is 28.6 kg in men and 16.4 kg in women. The measurement was performed 1 month after discharge.

Measure: Hand grip strength

Time: 1 month after discharge from hospital

Secondary Outcomes

Description: Short form - 36 measures health related quality of life. It is a self-reported survey that evaluates individual health status with eight parameters consisting of physical function, pain, role limitations attributed to physical problems, role limitations attributed to emotional problems, mental health, social functioning, energy/ vitality, general health perception. There is not a summary score, each section is scored between 0-100, 0 indicates the worst condition, 100 indicates the best. The measurement was performed 1 month after discharge.

Measure: Short form - 36

Time: 1 month after discharge from hospital

Description: Number of days of stay in intensive care unit from admission to discharge

Measure: Length of stay in intensive care unit

Time: through study completion, an average of 3 months

Description: Number of days of stay in hospital from admission to hospital to discharge from hospital

Measure: Length of stay in hospital

Time: through study completion, an average of 3 months

Description: Number of days of invasive mechanical ventilation during intensive care unit

Measure: Duration of invasive mechanical ventilation

Time: through study completion, an average of 3 months

Description: Manual muscle strength was graded via a composite of Medical Research Council Scale score which has an excellent inter-rater reliability in survivors of critical illness. This scale range from 0 point (no muscle contraction) to 5 points (normal muscle strength). Through examination of 3 muscle groups in each limb (arm abduction, forearm flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexion), clinical important muscle weakness has been defined as a composite score < 48 out of maximum 60 points. The measurement was performed 1 month after discharge.

Measure: Manual muscle strength

Time: 1 month after discharge from hospital

Description: Range of joint motion was evaluated in upper and lower extremity joints by physical examination and the results were recorded as normal or restricted for each joint. The measurement was performed 1 month after discharge.

Measure: Range of joint motion

Time: 1 month after discharge from hospital
79 Effectiveness of Convalescent Immune Plasma Therapy in Severe COVID-19 Patients With Acute Respiratory Distress Syndrome

The aim of the study is to evaluate the safety, improvement of clinical symptoms and laboratory parameters of convalescent immune plasma treatment in severe Covid-19 patients with ARDS.

NCT04442958
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Other: Convalescent Immune Plasma
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Acute phase reactant

Measure: Plasma ferritin level

Time: 7. day

Description: Infection markers

Measure: Lymphocyte count

Time: 7. day

Description: Hypercoagulability

Measure: D-Dimer level

Time: 7. day

Description: Infection markers

Measure: C-Reactive protein level

Time: 7. day

Description: Infection markers

Measure: Plasma procalcitonin level

Time: 7. day

Description: Coagulopathy

Measure: Plasma fibrinogen level

Time: 7. day

Secondary Outcomes

Description: Arterial oxygenation

Measure: Fractional Inspired Oxygen Level

Time: 7. day

Description: Arterial oxygenation

Measure: Partial Oxygen Saturation level

Time: 7. day

Description: Arterial oxygenation

Measure: Arterial Oxygen level

Time: 7. day
80 Evaluation of Physical Activity Level and Sleep Quality in Patients With Obstructive Sleep Apnea Syndrome During Covid-19 Pandemic

As long as the people stay at home because of the Covid 19 outbreak, the investigators assume that the sleep quality of OUAS patients, like everyone else, and the sleep quality of COVID-19 outbreak are reduced due to anxiety and anxiety in people. In addition, we assume that sleep quality and physical activity level are related to health literacy level and fear of movement (kinesiophobia). In this study; the investigators aimed to determine how patients are affected by this process by evaluating sleep quality, physical activity, fear of movement and health literacy in OSAS patients during our stay in the COVID-19 outbreak.

NCT04451993
Conditions
  1. Obstructive Sleep Apnea-hypopnea Syndrome
MeSH:Sleep Apnea Syndromes Sleep Apnea, Obstructive Syndrome
HPO:Obstructive sleep apnea Sleep apnea

Primary Outcomes

Description: International Physical Activity Questionnaire/ In activity-specific scoring, walking under the heading of the fields is calculated by the sum of the moderate intensity activity and intensive activity in itself. From these calculations, a score is obtained in MET-minutes. There are 3 categories of physical activity level classification. Physical activity levels are classified as physically inactive (inactive), low level of physical activity (minimally active) and sufficient level of physical activity (very active)

Measure: Physical Activity

Time: 1 day

Description: The Pittsburgh Sleep Quality Index

Measure: Sleep Quality

Time: 1 day

Secondary Outcomes

Description: In order to measure the general sleepiness of people during the day, it was evaluated with a standard questionnaire, which is defined as Epworth sleepiness scale (EUS) and consists of 8 questions. The answers for each question are scored between 0 and 3 and the total score is obtained. The score obtained above 10 in EUS has high sensitivity and specificity for daytime sleepiness.

Measure: Daytime Sleepiness

Time: 1 day

Description: Tampa Kinesiophobia Scale (TKS)The person gets a total score between 17-68. The high score on the scale indicates that kinesiophobia is also high

Measure: Fear of movement

Time: 1 day

Description: Translated into Turkish TURKEY health literacy SCALE-32 (Tsoy-32) will be used. It was used to evaluate the literacy rates of individuals over the age of 15. 0 indicates the lowest health literacy and 50 indicates the highest health literacy.

Measure: Health literacy

Time: 1 day

Other Outcomes

Description: In the human circadian rhythm, the Morning Morning-Evening Survey (SAA) form was used, which determined morning and evening types.

Measure: Circadian rhythm evaluation

Time: 1 day
81 A Phase 1 Study of the Safety and Tolerability of BX-U001 for the Treatment of Severe COVID-19 Pneumonia With Moderate to Severe Acute Respiratory Distress Syndrome (ARDS).

This is an open-label, single-arm, dose-escalating study to evaluate the safety and explore the dose limiting toxicity and maximum tolerated dose of a human umbilical cord derived mesenchymal stem cell product (BX-U001) in severe COVID-19 pneumonia patients with acute respiratory distress syndrome (ARDS). Qualified subjects after the screening will be divided into low, medium, or high dose groups to receive a single intravenous infusion of BX-U001 at the dose of 0.5×10^6, 1.0×10^6, or 1.5×10^6 cells/kg of body weight, respectively.

NCT04452097
Conditions
  1. COVID-19
  2. ARDS
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Human umbilical cord mesenchymal stem cells + best supportive care
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Safety will be defined by the incidence of infusion-related adverse events as assessed by the treating physician

Measure: Incidence of infusion-related adverse events

Time: Day 3

Description: Safety will be defined by the incidence of TEAEs and TESAEs as assessed by the treating physician

Measure: Incidence of any treatment-emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)

Time: Day 28

Secondary Outcomes

Description: The dose will be selected based on the assessment of dose-limiting toxicity and maximum tolerated dose.

Measure: Selection of an appropriate dose of the hUC-MSC product for the following Phase 2 study

Time: Day 28
82 Tissue Plasminogen Activator (tPA) Treatment for an Atypical Acute Respiratory Distress Syndrome (Microvascular COVID-19 Lung Vessels Obstructive Thromboinflammatory Syndrome (MicroCLOTS): A Multicentral Randomized Trial (AtTAC-trial)

At the beginning COVID-associated lung injury was considered as typical ARDS, hence respiratory and nonrespiratory treatments were delivered according to general principles for this kind of illness. There is hypothesis that in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. The investigators suggest that thrombolytic therapy may be beneficial when compared to standard care in patients with SARS-CoV-2 and severe respiratory failure.

NCT04453371
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Tissue plasminogen activator
  2. Drug: Ringer solution
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: P/F (PaO2/FiO2) change during the first 72hrs after the end of the procedure in adult patients with severe atypical ARDS caused by SARS-2-CoV.

Time: Each 6 hours during first 3 days after the end of thrombolysis procedure.

Secondary Outcomes

Description: Calculated as 28 days - number of days when patient receive any kind of ventilatory support (MV + SV + NIV).

Measure: Ventilator-free time (days free from MV) for 28 days of observation.

Time: 28 days

Other Outcomes

Measure: Mortality in 28 days and 1 year after randomization despite of the reason.

Time: 28 days, 1 year after randomization

Description: Number of days when patient was in ICU

Measure: Length of stay in the ICU

Time: 28 days

Description: Number of days when patient was in hospital

Measure: Length of stay in hospital

Time: 28 days

Measure: The time needed for "improvement of 2 points" according to WHO "Ordinal Scale for Clinical Improvement"

Time: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 month

Measure: Chest radiographs on a daily basis and define barotrauma as the presence of new pneumothorax, pneumomediastinum, pneumoperitoneum, or subcutaneous emphysema.

Time: Daily up to extubation than once a week/or on attending intensivist's discretion up to 1 month

Measure: Blood Pressure in millimetres of mercury

Time: Each 4 hours during first 2 weeks after the end of thrombolysis procedure.

Measure: Heart Rate in beats per minute

Time: Each 4 hours during first 2 weeks after the end of thrombolysis procedure.

Measure: Blood Oxygen Saturation

Time: Each 4 hours during first 2 weeks after the end of thrombolysis procedure.

Measure: ECG Q-wave

Time: Each 24 hours during first 2 weeks after the end of thrombolysis procedure.

Measure: ECG ST-segment

Time: Each 24 hours during first 2 weeks after the end of thrombolysis procedure.
83 Intermediate-size Expanded Access of Remestemcel-L, Human Mesenchymal Stromal Cells, for Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Coronavirus Disease (COVID-19)

The objectives of this intermediate-size expanded access protocol are to assess the safety and efficacy of remestemcel-L in participants with MIS-C associated with COVID-19.

NCT04456439
Conditions
  1. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Coronavirus Disease (COVID-19)
Interventions
  1. Biological: Remestemcel-L
  2. Drug: Hydrocortisone
  3. Drug: Diphenhydramine
MeSH:Coronavirus Infections Syndrome

84 Multi-center, Randomized, Placebo Controlled, Interventional Phase 2A Clinical Trial Evaluating the Safety and Potential Efficacy of Multiple Dosing of Mesenchymal Stromal Cells in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2)

This is a multi-center, randomized, placebo controlled, interventional phase 2A trial to evaluate the safety profile and potential efficacy of multi-dosing of mesenchymal stromal cells (MSC) for patients with SARS-CoV-2 associated Acute Respiratory Distress Syndrome (ARDS). After informed consent, treatment assignment will be made by computer-generated randomization to administer either MSC or vehicle placebo control with a 2:1 allocation to the MSC: placebo arm.

NCT04466098
Conditions
  1. Acute Respiratory Distress Syndrome
  2. ARDS (Moderate or Severe)
  3. COVID-19 Pneumonia
Interventions
  1. Biological: Mesenchymal stromal cells
  2. Other: Placebo
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

Measure: Incidence of grade 3-5 infusional toxicities and predefined hemodynamic or respiratory adverse events related to the infusion of MSC

Time: Within 6 hours of the start of the infusion

Secondary Outcomes

Measure: Incidence of a reduction in one or more biomarkers of inflammation by day 7

Time: Day 7 after first infusion

Measure: Trend changes in PaO2:FiO2 ratio

Time: On the day of screening and on days 3, 7 and 14 after first infusion

Measure: Trend changes in Mean Airway Pressure

Time: On the day of screening and on days 3, 7 and 14 after first infusion

Measure: Trend changes in peak pressure

Time: On the day of screening and on days 3, 7 and 14 after first infusion

Measure: Trend changes in plateau pressure

Time: On the day of screening (baseline) and on days 3, 7 and 14 after first infusion

Measure: Trend changes in Positive end-expiratory airway pressure (PEEP)

Time: On the day of screening and on days 3, 7 and 14 after first infusion

Measure: Incidence of mortality

Time: 28 days after first infusion

Measure: Incidence of mortality

Time: 100 days after first infusion

Measure: Number of ICU-free days

Time: 28 days after first infusion

Measure: Number of days alive and ventilator free composite score 3

Time: 28 days after first infusion

Description: Acute Lung Injury Score is a composite 4 point scoring system validated by the NHLBI ARDS Network that considers PaO2/FiO2, the level of positive end-expiratory airway pressure, respiratory compliance, and the extent of pulmonary infiltrates on the chest radiograph

Measure: Change in acute lung injury (ALI) score 2

Time: Baseline and Day 28 after first infusion

Measure: Incidence of serious adverse events

Time: 28 days after first infusion

Measure: Number of days alive off supplemental oxygen

Time: 100 days after first infusion
85 A Multi-Centre, Open Label, Two Arm Randomized, Pivotal Phase 2 Trial to Study the Efficacy and Safety of Itolizumab in COVID-19 Complications

Randomized, Parallel Group, Active Controlled Trial

NCT04475588
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Cytokine Release Syndrome
  3. Covid19
Interventions
  1. Drug: Itolizumab IV infusion
  2. Drug: Best supportive care" which includes antivirals /antibiotics/ hydroxychloroquine; oxygen therapy
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Synd Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: 1-month mortality is defined as the ratio of patients who will live after 1 month from study start out of those registered at baseline

Measure: One-month mortality rate between the two arms

Time: One-month

Secondary Outcomes

Description: Baseline, during treatment, One month

Measure: Biomarkers (IL-6, TNF-a, IL1, IL17, etc…)

Time: One Month

Description: Baseline, during treatment (Before every dose and 12 h post dose) up to 1 month

Measure: Lymphocyte count

Time: One Month

Description: Baseline, during treatment (Before every dose and 12 h post dose) up to 1 month

Measure: CRP (C-reactive protein) level

Time: One Month

Description: Baseline, during treatment (Before every dose and 12 h post dose) up to 1 month

Measure: PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)

Time: One Month

Description: At baseline, after seven days and if clinically indicated (up to 1 month)

Measure: Radiological response

Time: one month

Description: from baseline up to patients discharge (up to 1 month)

Measure: Duration of hospitalization

Time: One Month

Description: up to 1 month

Measure: Remission of respiratory symptoms

Time: One Month
86 Managed Access Program (MAP) to Provide Access to Canakinumab Treatment of Cytokine Release Syndrome (CRS) in Patients With COVID-19-induced Pneumonia

This is a global Managed Access Program (MAP) to provide access to canakinumab to patients with cytokine release syndrome resulting from COVID-19 pneumonia

NCT04476706
Conditions
  1. Cytokine Release Syndrome in COVID-19-induced Pneumonia
Interventions
  1. Drug: canakinumab
MeSH:Pneumonia Syndrome
HPO:Pneumonia

87 Randomized, Double-Blind Clinical Trial of Ruxolitinib in Patients With Acute Respiratory Disorder Syndrome Due to SARS-CoV-2 Infection

The COVID-19 pandemic has had a dramatic effect in public health worldwide. In Brazil, there have been more than 2 million confirmed cases and over 75,000 deaths since February 26, 2020. Based on reports of a hyperinflammatory state associated with COVID-19, the use of immunosuppressive drugs may be efficacious in the treatment of this disease. JAK inhibitors have been shown to harness inflammation in a number of different pathologic conditions. The aim of the present study is to evaluate the efficacy and safety of JAK inhibitor ruxolitinib in patients with acute respiratory distress syndrome due to COVID-19.

NCT04477993
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
  2. SARS-CoV2
Interventions
  1. Drug: Janus Kinase Inhibitor (ruxolitinib)
  2. Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiration Disorders Respiratory Tract Diseases Syndrome

Primary Outcomes

Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 14.

Time: 14 days

Secondary Outcomes

Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 28

Time: 28 days

Description: ICU admission, mechanical ventilation, death or consent withdrawal

Measure: Time to treatment failure

Time: 28 days

Measure: Overall survival at days 14 and 28

Time: 14 and 28 days

Measure: Cumulative incidence of ICU admission rate at days 14 and 28

Time: 14 and 28 days

Measure: Cumulative incidence of mechanical ventilation at days 14 and 28

Time: 14 and 28 days

Measure: Duration of hospital stay

Time: 28 days

Measure: Duration of ICU stay

Time: 28 days

Measure: Duration of mechanical ventilation

Time: 28 days

Measure: Duration of non-invasive ventilation

Time: 28 days

Measure: Secondary hemophagocytic syndrome rate

Time: 28 days

Measure: Cumulative incidence nosocomial infection rate at days 14 and 28

Time: 14 and 28 days

Measure: Incidence of discontinuation of oxygen supplementation at days 14 and 28

Time: 14 and 28 days

Measure: Rate of grade 1-2 and 3-5 emerging adverse events at day 28

Time: 28 days

Measure: Cumulative dose of methylprednisolone at days 14 and 28

Time: 14 and 28 days

Measure: Change in PaO2/FiO2 ratio from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in interleukin 6 levels [pg/mL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in d-dimer levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in fibrinogen levels [mg/dL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in ferritin levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in C reactive protein levels [mg/L] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in alanine aminotransferase [U/L] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in aspartate aminotransferase [U/L] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in creatinine levels [mg/dL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in glucose levels [mg/dL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in hemoglobin levels [g/dL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in platelet count [x10ˆ3/mmˆ3] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in absolute neutrophil count [x10ˆ3/mmˆ3] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in absolute neutrophil count [/mmˆ3] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in absolute lymphocyte count [/mmˆ3] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in prothrombin time ratio from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in partial thromboplastin time ratio from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in bilirubin [mg/dl] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in lactate dehydrogenase [U/L] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in CPK-MB [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in troponin [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in von Willebrand factor antigen level (VWF:Ag) [%] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in von Willebrand factor activity (ristocetin cofactor) [%] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in ADAMTS-13 [%] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in von Willebrand multimeters from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in plasminogen activator inhibitor-1 levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in E-selectin levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in P-selectin levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in endothelin [fmol/mL] from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in circulating microparticles from baseline to days 14 and 28

Time: 14 and 28 days

Measure: Change in thromboelastography from baseline to days 14 and 28

Time: 14 and 28 days
88 Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19)

The purpose of this study is to evaluate the efficacy of vadadustat for the prevention and treatment of acute respiratory distress syndrome (ARDS) in hospitalized patients with Coronavirus Disease 2019 (COVID-19).

NCT04478071
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Coronavirus Infection
Interventions
  1. Drug: vadadustat
  2. Drug: placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS): 8 - Death 7 - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 6 - Hospitalized, on non-invasive ventilation or high flow oxygen devices 5 - Hospitalized, requiring supplemental oxygen 4 - Hospitalized, not requiring supplemental oxygen - requiring ongoing care (COVID-19 related or otherwise) 3 - Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 2 - Not hospitalized, limitation on activities and/or requiring home oxygen 1 - Not hospitalized, no limitations on activities

Measure: Number of participants who are classified 8 (dead), 7 (hospitalized, on invasive mechanical ventilation or ECMO), or 6 (hospitalized, on non-invasive ventilation or high flow oxygen devices) on the NIAID ordinal scale

Time: day 14

Secondary Outcomes

Description: Modified Sequential Organ Failure Assessment (MSOFA) scale: Each of 5 organ systems is given a score of 0 to 4, as detailed below. The MSOFA scale total score is the sum of the score for the 5 organ systems. Discharged patients will be assigned a score of 0 and dead patients a score of 20. Respiratory oxygen saturation(SpO2)/concentration of oxygen that a person inhales(FiO2): 0 (> 400); 1 (≤ 400); 2 (≤ 315); 3 (≤ 235); 4 (≤ 150) Liver: 0 (No scleral icterus or jaundice); 3 (Scleral icterus or jaundice) Cardiovascular, hypotension: 0 (No hypotension); 1 (MAP < 70 mm Hg); 2 (Dopamine ≤ 5 or dobutamine any dose); 3 (Dopamine > 5, Epinephrine ≤ 0.1, Norepinephrine ≤ 0.1); 4 (Dopamine > 15, Epinephrine > 0.1, Norepinephrine > 0.1) Central Nervous System (CNS), Glasgow Coma Score: 0 (15), 1 (13 - 14); 2 (10 - 12); 3 (6 - 9); 4 (< 6) Renal, Creatinine mg/dL: 0 (< 1.2); 1 (1.2 - 1.9); 2 (2.0 - 3.4); 3 (3.5 - 4.9); 4 (> 5.0)

Measure: Number of participants with a total score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) scale

Time: day 14
89 A Randomized, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and in Combination With NA-831 in Healthy Volunteers

The clinical study is designed to evaluate the safety, tolerability and pharmacokinetics of inhaled nanoparticle nanoparticle formulation of Remdesivir (GS-5734) alone and in combination with NA-831 in 48 healthy volunteers.

NCT04480333
Conditions
  1. Covid19
  2. Corona Virus Infection
  3. Severe Acute Respiratory Syndrome
  4. Severe Acute Respiratory Infection
  5. Severe Acute Respiratory Syndrome (SARS) Pneumonia
  6. Severe Acute Respiratory Syndrome of Upper Respiratory Tract
  7. Neurodegeneration
  8. Neuroinflammatory Response
Interventions
  1. Drug: Drug: NA-831 - 0.10 mg/kg
  2. Drug: Placebo- 0.10 mg/kg
  3. Drug: Drug: NA-831 - 0.20 mg/kg
  4. Drug: Placebo- 0.20 mg/kg
  5. Drug: Drug: GS-5734 - 1.00 mg/kg
  6. Drug: Placebo- 1.00 mg/kg
  7. Drug: Drug: GS-5734 - 2.00 mg/kg
  8. Drug: Placebo- 2.00 mg/kg
  9. Combination Product: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)
  10. Combination Product: Placebo 0.10 mg + 1.00 mg/kg
  11. Combination Product: Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg)
  12. Combination Product: Placebo 0.20 mg + 2.00 mg/kg
MeSH:Infection Communicable Diseases Respiratory Tract Infections Virus Diseases Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome Nerve Degeneration
HPO:Neurodegeneration Pneumonia Respiratory tract infection

Primary Outcomes

Description: AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) V5.0

Measure: Proportion of Participants Experiencing any Treatment-Emergent Adverse Events

Time: First dose date up to Day 30 Follow-up Assessment

Description: This will be assessed at various time points by clinical laboratory tests and vital signs.

Measure: Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities

Time: First dose date up to Day 30 Follow-up Assessment

Secondary Outcomes

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the maximum concentration (Cmax) of NA-831 and GS-5734 in human serum.

Measure: Maximum Concentration (Cmax) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the time to maximum concentration (Tmax) of NA-831 and GS-5734 in human serum

Measure: Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve from time of administration to the last measurable of NA-831 and GS-5734

Measure: AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve extrapolated to infinity (AUC0-∞) of NA-831 and GS-5734

Measure: Area Under the Curve Extrapolated to Infinity (AUC0-∞)

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the half-life (t1/2) of NA-831 and GS-5734 in human serum.

Measure: Half-Life (t1/2) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera through various time points to elucidate the volume of distribution (Vd) of NA-831 and GS-5734 in human serum.

Measure: Volume of Distribution (Vd) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera through at various time points to elucidate clearance [CL] of NA-831 and GS-5734 in human serum.

Measure: Clearance [CL] - Pharmacokinetic Assessment

Time: 7 days
90 Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of Acute Respiratory Distress Syndrome (RAPA-CARDS)

This study assesses the clinical effectiveness of mammalian target of rapamycin (mTOR) inhibition with rapamycin in minimizing or decreasing the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in participants infected with mild to moderate COVID-19 virus.

NCT04482712
Conditions
  1. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
  2. Respiratory Failure
  3. Sars-CoV2
Interventions
  1. Drug: Rapamycin
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury Syndrome

Primary Outcomes

Description: The proportion of participants who survive without respiratory failure

Measure: Survival rate

Time: 4 weeks

Secondary Outcomes

Description: The WHO ordinal scale is a measure of clinical improvement using a scale score of 0-8, where 0 indicates a better outcome and 8 indicates death: Uninfected, no clinical oor virological evidence of infection 0 Ambulatory, no limitation of activities 1 Ambulatory, limitation of activities 2 Hospitalized Mild disease, no oxygen therapy 3 Hospitalized mild disease, oxygen by mask or nasal prongs 4 Hospitalized Severe Disease, non-invasive ventilation 5 Hospitalized severe disease, intubation and mechanical ventilation 6 Hospitalized severe disease, ventilation+organ support 7 Death 8

Measure: Change in Clinical Status assessed by the World Health Organization (WHO) scale

Time: Baseline to 4 weeks

Description: An ordinal scale for clinical improvement scored from 1 to 8, where 1 represents death and 8 represents recovery to discharge from hospital with no limitation on activities: Death (1) Hospitalized, on invasive mechanical ventilation of extracorporeal membrane oxygenation (ECMO) (2) Hospitalized, on non-invasive ventilation or high flow oxygen devices (3) Hospitalized, requiring supplemental oxygen (4) Hospitalized, not requiring supplemental oxygen or ongoing medical care (6) Not hospitalized, limitation on activities &/or requiring supplemental home oxygen (7) Not hospitalized, no limitation on activities (8)

Measure: Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale

Time: Baseline to 4 weeks

Other Outcomes

Description: Total number of deaths during the study period

Measure: All cause mortality

Time: 4 weeks

Description: Number of days on ECMO

Measure: Duration of ECMO

Time: Up to 4 weeks

Description: Number of days participants are on supplemental oxygen

Measure: Duration of supplemental oxygen

Time: Up to 4 weeks

Description: Days of hospitalization

Measure: Length of hospital stay

Time: Up to 4 weeks

Description: Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)

Measure: Length of time to SARS-CoV2 negativity

Time: Up to 4 weeks
91 Telemedicine Follow-up for Post-Acute Coronary Syndrome Patients

The aim is to compare the safety of using telemedicine and office visit follow-up in post-acute coronary syndrome patients

NCT04485754
Conditions
  1. ACS - Acute Coronary Syndrome
Interventions
  1. Other: Telemedicine FU
  2. Other: Office FU
MeSH:Acute Coronary Syndrome Syndrome

Primary Outcomes

Description: Major adverse cardiac and cerebrovascular events: cardiac death, myocardial infarction, or stroke

Measure: MACCE

Time: 1 year

Secondary Outcomes

Description: High Level of Medical Therapy Optimization is defined as a participant meeting all of the following goals: LDL < 1.4 mmol/L and on any statin, blood pressure < 140/90 mm/Hg (<135/85 mm/Hg for patients with diabetes mellitus), on aspirin or other antiplatelet or anticoagulant, and not smoking. High level of medical therapy optimization is missing if any of the individual goals are missing.

Measure: High level of MT optimization

Time: 1 year

Description: Blood pressure < 140 mm/Hg (<135/85 mm/Hg for for patients with diabetes mellitus)

Measure: PB < 140/90 mm/Hg (<135/85 mm/Hg for Diabetes)

Time: 1 year

Description: Low density lipoprotein< 1.4 mmol/L

Measure: LDL < 1.4 mmol/L

Time: 1 year

Description: Not smoking

Measure: Not smoking

Time: 1 year

Description: Decrease in overweight

Measure: Decrease in overweight

Time: 1 year

Description: Adherence to aspirin or other antiplatelet or anticoagulant

Measure: Aspirin or other antiplatelet or anticoagulant

Time: 1 year

Description: Adherence to prescribed at discharge medication

Measure: Adherence to prescribed medication

Time: 1 year

Description: Hospitalization for cardiac reasons

Measure: Hospitalization

Time: 1 year
92 Clinical Outcome of Anti-IL6 vs Anti-IL6 Corticosteroid Combination in Patients With SARS-CoV-2 Cytokine Release Syndrome

The cytokine storms mediated by over production of proinflammatory cytokines have been observed in a large population of critically ill patients infected with COVID-19. Patients diagnosed with cytokine storms progress to cardiovascular collapse, multiple organ dysfunction and death rapidly. Therefore, early identification, treatment and prevention of the cytokine storms are of crucial importance for the patients. Immuomedulator such as interleukin-6 (IL-6) antagonist, emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms recently. In this study, we aimed to evaluate the safety and efficacy of anti-IL6 alone vs anti-IL6 corticosteroid combination in patients with COVID-19 pneumonia

NCT04486521
Conditions
  1. Critical Illness
  2. Corona Virus Infection
  3. Cytokine Release Syndrome
Interventions
  1. Drug: Interleukin 6 (IL6) Antagonist
  2. Drug: Interleukin 6 (IL6) Antagonist and corticosteroids
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome Critical Illness

Primary Outcomes

Description: The median ventilator-free days will be calculated as calendar days with no ventilator support to day 28 . Participants who die before day 28 are assigned zero free days.

Measure: Ventilator-Free Days

Time: Up to Day 28

Secondary Outcomes

Description: From Intubation to extubation date and off Mechanical Ventilation or until ICU discharge, death, or 28 days whichever occurs first.

Measure: Median duration of ventilation

Time: Up to Day 28

Description: Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2)

Measure: Median change in the PaO2/FiO2

Time: Up to Day 28

Description: The median vasopressor-free days will be calculated as calendar days with no vasopressor support to day 28. Participants who die before day 28 are assigned zero free days.

Measure: Vasopressor-Free days

Time: Up to Day 28

Description: To compare ICU LOS

Measure: Duration of ICU Stay

Time: Up to 28 days

Description: To compare hospital LOS

Measure: Duration of Hospital Stay

Time: Up to 28 days

Description: Death that occurs during 28 days

Measure: Mortality Rate

Time: Up to Day 28

Description: adverse events that occurs during 28 days

Measure: Percentage of participants with adverse events [transaminitis, hyperglycemia]

Time: Up to 28 days

Description: Concentration of inflammatory markers

Measure: Concentration of Ferritin, IL6, D dimer, fibrinogen, C-reactive protein (CRP), Lactate dehydrogenase (LDH) and absolute lymphocyte count and their correlation with the effectiveness of the treatment

Time: Up to 28 days

Measure: Rate of superinfection (bacterial, viral, invasive fungal infections)

Time: Up to 28 days

Measure: Time to the first COVID 19 test negative

Time: Up to 28 days
93 COVID-19 Virtual Post Intensive Care Syndrome (CoV-PICS) Clinic: Modern, Convenient and Practical Recovery Care

This is a pilot study to evaluate the feasibility of a COVID-19 virtual Post Intensive Care Syndrome (PICS) clinic (CoV-PICS). The findings from this study are the first steps in determining the feasibility and potential impact of a telehealth PICS clinic that is able to address the needs of patients with COVID-19 disease and potentially other patients that are unable to attend a brick and mortar clinic and require virtual care.

NCT04490278
Conditions
  1. Post ICU Syndrome
Interventions
  1. Other: Medical Record Review - Inpatient Treatment
  2. Other: Online Questionnaires
MeSH:Syndrome

Primary Outcomes

Description: Acceptability of Intervention Measure (AIM) Implementation of outcome measure. Response Scale: 1 = Completely disagree, 2 = Disagree, 3 = Neither agree nor disagree, 4 = Agree, 5 = Completely agree

Measure: Acceptance with virtual CoV-PICS Visits - AIM

Time: up to 6 months after consent

Description: Intervention Appropriateness Measure (IAM) Implementation of outcome measure. Response Scale: 1 = Completely disagree, 2 = Disagree, 3 = Neither agree nor disagree, 4 = Agree, 5 = Completely agree

Measure: Acceptance with virtual CoV-PICS Visits - IAM

Time: up to 6 months after consent

Description: Feasibility of Intervention Measure (FIM) Implementation of outcome measure. Response Scale: 1 = Completely disagree, 2 = Disagree, 3 = Neither agree nor disagree, 4 = Agree, 5 = Completely agree

Measure: Acceptance with virtual CoV-PICS Visits - FIM

Time: up to 6 months after consent

Secondary Outcomes

Description: Katz Independence in Activities in Daily Living Rates daily activities by independence or dependence in completing the task (range 0-6) 0=low or patient very dependent, 6 = high or patient independent

Measure: PICS Symptoms - Daily living

Time: Up to 6 months after consent

Description: Montreal Cognitive Assessment (MoCA) Screening tool for mild cognitive dysfunction. Sum all subscores listed on the right-hand side, for a possible maximum of 15 points. A final total score of 11 and above is considered normal.

Measure: PICS Systems - Cognitive

Time: Up to 6 months after consent

Description: Scored Patient-Generated Subjective Global Assessment (PG-SGA) The Scored PG-SGA© includes the four patient-generated historical components (Weight History, Food Intake, Symptoms and Activities and Function - also known as the PG-SGA Short Form©), the professional part (Diagnosis, Age, Metabolic stress, and Physical Exam), the Global Assessment (A = well nourished, B = moderately malnourished or suspected malnutrition, C = severely malnourished), the total numerical score, and nutritional triage recommendations.

Measure: PICS Systems - Nutrition

Time: Up to 6 months after consent

Description: Patient-Reported Outcomes Measurement Information System (PROMIS 29) PROMIS Profile instruments are a collection of short forms containing a fixed number of items from seven PROMIS domains (Depression, Anxiety, Physical Function, Pain Interference, Fatigue, Sleep Disturbance, and Ability to Participate in Social Roles and Activities). The PROMIS-29 assesses each of the 7 domains with 4 questions. Range 1=Never, 2=rarely, 3=sometimes, 4=often, 5=always

Measure: PICS Systems - PROMIS

Time: Up to 6 months after consent

Description: ICU Memory Tool 4 item questionnaire of patient's memory of ICU stay. Response scale: factual memories (range 0-11), memories of feelings (range 0-6), delusional memories + 1 for mention of nurse or doctor trying to kill the patient in description (range 0-6)

Measure: PICS Symptoms - Memory

Time: up to 6 months after consent
94 Mechanical Ventilation Strategy for Coronavirus Disease 2019 (COVID-19) - COVEN Study

This is a prospective, randomized, single-center, open-label controlled trial, designed to compare the efficacy of two ventilation strategies (Low Tidal Volume and positive end-expiratory pressure (PEEP) based on the Acute Respiratory Distress Syndrome (ARDS) Network low PEEP-fraction of inspired oxygen inspired oxygen fraction (FIO2) Table versus Low Driving Pressure and PEEP guided by Electrical Impedance Tomography (EIT) in reducing daily lung injury score in patients with acute respiratory distress syndrome caused by COVID-19. The two strategies incorporate different prioritizations of clinical variables. The PEEP-FIO2 table strategy aims to reduce lung overdistension, even if it requires tolerating worse gas exchange. EIT-guided strategy prioritizes mechanical stress protection, avoiding alveolar overdistension and collapse.

NCT04497454
Conditions
  1. Respiratory Distress Syndrome
  2. Severe Acute Respiratory Syndrome Due to Coronavirus (SARS-CoV2)
  3. Mechanical Ventilation
Interventions
  1. Other: EIT-Group
  2. Other: ARDSNet
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Syndrome

Primary Outcomes

Description: This score originally ranges from 0 to 4 points based on the average of 4 parameters (PaO2/FiO2, chest X-Ray, PEEP level, and Respiratory compliance). In the modified version, if the patient dies, he or she automatically receives a score of 5 irrespective of the other four parameters. If the patient is extubated, the score is automatically zero. We also substituted FiO2 for PEEP guaranteeing equivalence of the score when either the low or high PEEP-FiO2 table is applied.

Measure: Average daily Modified Lung injury score until day 28

Time: daily

Secondary Outcomes

Description: Number of days with less than or equal to 1 Liter/min of oxygen supplementation until day 28

Measure: High oxygen dependence free days until day 28

Time: 28 days

Description: Number of days free of mechanical ventilation assistance after protocol inclusion and before day 28

Measure: Mechanical ventilation free days until day 28

Time: 28 days

Description: Occurrence of shock (persistent hypotension despite rescue measures) and incidence of barotrauma

Measure: Incidence of shock or barotrauma

Time: 28 days

Description: Occurrence of acute renal failure that justifies renal replacement therapy

Measure: Incidence of acute renal failure requiring renal replacement therapy

Time: 28 days

Description: Percentage of patients who died in each arm up to 28 days

Measure: 28-day mortality

Time: 28 days
95 Multicenter, Open-label, Randomised Trial to Assess the Efficacy and Tolerability of Poractant Alfa(Porcine Surfactant, Curosurf®) in Hospitalized Patients With SARS-COV-19 Acute Respiratory Distress Syndrome (ARDS)

The purpose of this Phase II -Proof of Concept study is to evaluate the efficacy and safety of poractant alfa (Curosurf®), administered by endotracheal (ET) instillation in adult hospitalized patients with SARS-COV-19 acute respiratory distress syndrome (ARDS)

NCT04502433
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: CUROSURF® (poractant alfa)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: The primary outcome variable will be the number of ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation during the 21 days following randomisation.

Measure: number of ventilator-free days

Time: up to 21 days

Secondary Outcomes

Measure: Number of free days from invasive ventilation

Time: up to 21 days

Measure: Number of free days from non-invasive ventilation (NIV)

Time: up to 21 days

Measure: Change from baseline in PaO2/FiO2 ratio measured at 6 hours and 12 hours following administration of each dose in the treated group and at the similar timepoints in the control group

Time: 6, 12, 30, 36, 54 and 60 hours after randomisation

Measure: Change from baseline in PaO2/FiO2 ratio at additional timepoints

Time: every 24 hours after treatment/randomisation until the patient is discharged from the ICU . Up to 28 days

Measure: Length of ICU stay (days)

Time: up to 28 days

Measure: Mortality at Day 28

Time: Day 28

Measure: Change from baseline in ventilatory parameter (Tidal volume (TV))

Time: up to 28 days

Description: min score 0 max score 24

Measure: Delta Sequential Organ Failure Assessment (SOFA) Score

Time: up to 28 days

Measure: Incidence of all the AEs, AEs related to poractant alfa (treated cohort) (ADRs), serious AEs (SAEs) and AEs leading to death

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (pH)

Time: up to 28 days

Measure: Percentage of patients with PaO2/ FiO2 improvement of >20% following administration of each dose in the treated group and at similar timepoints in the control group

Time: at 6 and 12 hours following administration each dose in the treated group and at similar timepoints in the control group = up to 60 hours after the randomization

Measure: Number of Extracorporeal Membrane Oxygenation (ECMO)-free days- (only for cohort 2 of patients in ECMO)

Time: 21 days after randomization

Measure: Change from baseline in FiO2

Time: (6, 12, 30, 36, 54 and 60 hours after randomisation + every 24 hours after treatment/randomisation until the patient is discharged from the ICU = up to 28 days

Measure: Change from baseline in ventilatory parameter (respiratory rate (RR))

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (dynamic compliance (Cdyn))

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (static compliance (Cstat))

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (positive end-expiratory pressure (PEEP)

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (peak inspiratory pressure (PIP))

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (plateau pressure (Pplat))

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (pCO2)

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (pO2)

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (HCO3)

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (lactate)

Time: up to 28 days
96 The Usability, Feasibility, and Tolerability of Virtual Reality for Rehabilitation From COVID-19: An Explorative Study

Patients who receive intensive care are known to be at high risk for physical, psychological, and cognitive impairments, a constellation known as PICS. COVID-19 patients are expected to have high chances of suffering from PICS (PICS-COV) as they frequently require several weeks of intensive care and traditional PICS preventive measures are virtually impossible due to infection control precautions, prone positioning, and deprivation of social contact. To prevent PICS after ICU discharge in COVID-19 patients, physical therapy is recommended. From recent but limited experience it appears that even patients with COVID-19 who have not been admitted to the ICU can suffer from impairments in the same domains and sometimes to a similar degree of severity. Also for these patient group rehabilitation seems warranted. Yet, the resources needed to provide rehabilitation treatment to COVID-19 patients are inadequate because healthcare systems faced a shortage of high-quality treatment for these impairments already before the COVID-19 crisis emerged. Virtual Reality (VR) provides potential to healthcare practitioners to administer fast, temporary, and tailor-made rehabilitation services at a distance, and offers a solution to address the impending surge of demand for rehabilitation after COVID-19 infection. VR consists of a head mounted display (HMD) that can bring the user by computer-generated visuals into an immersive, realistic multi-sensory environment. Current VR technology is accessible, easy in use for a large audience, and safe in use. There already exist multiple VR applications for providing physical, psychological, and cognitive rehabilitation. These applications have been brought together in a VR suite for rehabilitation after COVID-19. Patients visiting a physiotherapist for rehabilitation from COVID-19 will be asked to participate in this study. They receive a VR HMD for training purposes. This study aims to understand the usability, feasibility, and tolerability of VR for rehabilitation after COVID-19, and to pilot the effectiveness of VR improving the physical ability, mental and cognitive status of patients.

NCT04505761
Conditions
  1. Coronavirus
  2. Post Intensive Care Unit Syndrome
Interventions
  1. Device: Virtual Reality
MeSH:Coronavirus Infections Syndrome

Primary Outcomes

Description: At the end of the study, 15 patients will be interviewed about their experiences using VR for rehabilitation from COVID-19. The interview will be semi-structured, including questions on usability, tolerability and efficacy of VR according to the patients. The interviews will be recorded, written out and coded by means of grounded theory analysis in Atlas.ti. Themes and subthemes will be constructed.

Measure: Semi-structured interview with 15 patients on their experiences of VR for rehabilitation from COVID-19.

Time: Day 42

Description: By means of digital tracking in the VR goggles, we aim to understand what games are used most often by the participants.

Measure: Use of VR

Time: Day 42

Description: At the end of the study, 10 physiotherapists will be interviewed about their experiences using VR for rehabilitation from COVID-19. The interview will be semi-structured, including questions on usability, tolerability and efficacy of VR according to the physiotherapists. The interviews will be recorded, written out and coded by means of grounded theory analysis in Atlas.ti. Themes and subthemes will be constructed.

Measure: Semi-structured interviews with physiotherapists on their experiences of VR for rehabilitation from COVID-19.

Time: Day 42

Secondary Outcomes

Description: To investigate whether adding VR to rehabilitation (perceivably) improves physical performance, we use a baseline performance test as constructed by the COVID-19 recommendations (RL 2.0) as issued by the Royal Dutch Society for Physical Therapy (KNGF). Measurements will be done at the start of the intervention period and the end of the intervention period for tracking progress. The baseline performance test consists of several items of which the patient specific complaints is the first. Patient specific complaints refer to complaints the patients aim to improve by means of physiotherapy. Outcomes are qualitative outcomes.

Measure: Change in baseline performance test (guidelines KNGF) - Patient specific complaints.

Time: Day 0, day 42

Description: To investigate whether adding VR to rehabilitation (perceivably) improves physical performance, we use a baseline performance test as constructed by the COVID-19 recommendations (RL 2.0) as issued by the Royal Dutch Society for Physical Therapy (KNGF). Measurements will be done at the start of the intervention period and the end of the intervention period for tracking progress. The baseline performance test consists of several items of which the 6 minute walk test is the second. The 6 minute walk test studies the physical capacity of a patient. We measure at day 0 how many meter a patient can walk in 6 minutes and compare this to the meters a patient is able to walk at day 42.

Measure: Change in baseline performance test (guidelines KNGF) - 6 minute walk test

Time: Day 0, Day 42

Description: To investigate whether adding VR to rehabilitation (perceivably) improves physical performance, we use a baseline performance test as constructed by the COVID-19 recommendations (RL 2.0) as issued by the Royal Dutch Society for Physical Therapy (KNGF). Measurements will be done at the start of the intervention period and the end of the intervention period for tracking progress. The baseline performance test consists of several items of which hand grip strength is the third. The hand grip strength is measured by the One-repetition maximum test which measures the amount of kg's a patient can grip at his peakforce. Measurements are done at day 0 and day 42 and compared.

Measure: Change in baseline performance test (guidelines KNGF) - one-repetition maximum test

Time: Day 0, Day 42

Description: To investigate whether adding VR to rehabilitation (perceivably) improves physical performance, we use a baseline performance test as constructed by the COVID-19 recommendations (RL 2.0) as issued by the Royal Dutch Society for Physical Therapy (KNGF). Measurements will be done at the start of the intervention period and the end of the intervention period for tracking progress. The baseline performance test consists of several items of which the 30 sec sit to stand test for lower extremities is the fourth. The 30 seconds sit to stand test is for testing leg strength and endurance. A patient has to do as many sit to stand exercises in 30 seconds. Measurements are done at day 0 and compared to day 42.

Measure: Change in baseline performance test (guidelines KNGF) - 30 sec sit to stand

Time: Day 0, Day 42

Description: To investigate whether adding VR to rehabilitation (perceivably) improves physical performance, we use a baseline performance test as constructed by the COVID-19 recommendations (RL 2.0) as issued by the Royal Dutch Society for Physical Therapy (KNGF). Measurements will be done at the start of the intervention period and the end of the intervention period for tracking progress. The baseline performance test consists of several items of which the Borgscale for fatigue is the final item. The borgscale for fatigue is a numerical scale (1-10) to rate physical exertion and fatigue. Patients fill in the scale at day 0 and day 42. Results are compared.

Measure: Change in baseline performance test (guidelines KNGF) - Borgscale for fatigue

Time: Day 0, Day 42

Description: To investigate whether adding VR to rehabilitation (perceivably) improves physical performance, we will as well measure change in activities of Daily Life. This questionnaire (ADL) measures the ease of participating in activities of daily life (ADL) of the patient. The questionnaire consists of 22 questions ranging from 0 (not at all) to 3 (easily autonomous). Maximum score is 63.

Measure: Change in activities of daily life.

Time: Day 0, Day 42

Description: To investigate whether adding VR to rehabilitation (perceivably) improves psychological rehabilitation, we will measure change in HADS. The HADS (Hospital Anxiety and Depression Scale) is used to measure change in psychological outcomes before and after the intervention period. Questionnaire consists out of 14 questions with answers ranging from 0 (often) to 3 (almost never). All questions are summed up to a total of 42 points.

Measure: Change in HADS.

Time: Day 0, Day 42

Description: To investigate whether adding VR to rehabilitation (perceivably) improves cognitive rehabilitation, we will use the CFQ. The CFQ (Cognitive Failure Questionnaire) is used to measure change in cognitive outcomes before and after the intervention period. Questionnaire consists out 25 questions ranging from 0 to 5. All questions are summed up to a total of 100 points.

Measure: Change in CFQ.

Time: Day 0, Day 42

Description: To investigate whether adding VR to rehabilitation (perceivably) improves quality of life, we will use the SF12. The SF12 questionnaire is used to measure change in quality of life before and after the intervention period. SF12: SF12 measures via different scaled questions eight concepts: physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. The first four items together form the physical health scale. The latter four items form the mental health scale. The higher the scores, the better the physical and mental health. Highest possible score: 56. Lowest possible score: 12.

Measure: Change in SF12.

Time: Day 0, Day 42

Description: To investigate whether adding VR to rehabilitation (perceivably) improves quality of life, we will as well use the Positive Health questionnaire. The Positive Health questionnaire is used to measure change in quality of life before and after the intervention period. Positive Health:Positive health consists out of 42 statements separated in 6 categories: bodily functioning, mental functioning, spiritual dimension, quality of life, social participation, daily functioning. Each question should be rated with a 0 (worst) to a 10 (best). The higher the scores, the better the quality of life.

Measure: Change in positive health.

Time: Day 0, Day 42

Other Outcomes

Description: Age, gender, education, employment, lifestyle, experience with technology - qualitative measures.

Measure: Patient characteristics related to use of VR

Time: Day 0
97 Acute Kidney Injury In Subjects With Severe Acute Respiratory Syndrome Due to SARS-CoV2 Infection

Severe pneumoniae related to Coronavirus Disease (COVID-19), had a high in-hospital mortality; this condition are worst in subjects with acute kidney disease (AKI); conditioning increased mortality, days of assisted mechanical ventilation (AMV), increased nosocomial infections and high costs. We need many studies for determinated the risk factors for AKI in subjects with COVID-19. This study pretends identify the incidence of AKI in subjects with severe pneumoniae by COVID-19, describe the role of some biomarkers in the physiopathology of AKI-COVID-19; and determine the evolution of urinary biomarkers during hospitalization, like neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP7), and interleukin-6 (IL-6) and the progression of viruria of Severe Acute Respiratory Syndrome (SARS) related to CoronaVirus 2 (CoV2) in subjects with or without AKI.

NCT04517630
Conditions
  1. Coronavirus Infection
  2. Covid19
  3. SARS (Severe Acute Respiratory Syndrome)
  4. AKI
Interventions
  1. Diagnostic Test: urinary NGAL, TIMP-2, IGFBP7, IL-6, viral load and metabolomic
MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: To estimate the strength of association between the elevation of urinary levels of NGAL, TIMP-2, IGFBP7 and IL-6 and the development of AKI associated with SARS-CoV-2 pneumonia

Measure: Urinary levels of renal biomarkers

Time: Seven days

Secondary Outcomes

Description: Describe the incidence of AKI in critically ill patients with severe COVID-19 pneumonia

Measure: Incidence of AKI

Time: One month

Description: Estimate the strength of association of elevated urinary levels of NGAL, TIMP-2, IGFBP7 and IL-6 with mortality

Measure: Urinary levels of renal biomarkers and mortality

Time: 30 days

Description: Estimate the strength of association of elevated urinary levels of NGAL, TIMP-2, IGFBP7 and IL-6 with teh severity of the disease.

Measure: Urinary levels of renal biomarkers and severity of the disease.

Time: 30 days

Description: Identify possible risk factors (epidemiological, clinical, paraclinical, use of nephrotoxic agents) for the development of AKI in critically ill patients with COVID-19 pneumonia.

Measure: Risk factors for AKI in severe COVID-19

Time: 30 days

Description: Compare the evolution over time of renal function markers (NGAL, TIMP-2 and IGFBP7) in patients with and without kidney injury.

Measure: Evolution renal biomarkers

Time: 7 days

Description: Compare the evolution over time of the SARS-CoV-2 viral load in patients with and without acute kidney injury.

Measure: Evolution of viral load

Time: 7 days

Description: Analyze the complement pathway in urine and compare its evolution over time in patients with and without acute kidney injury and SARS-CoV-2 infection.

Measure: Evolution of complement pathway

Time: seven days

Description: Analyze the metabolomic profile in urine in patients with and without acute kidney injury with SARS-CoV-2 infection.

Measure: Metabolomic profile

Time: 7 days

Description: Describe partial arterial oxygen concentration/inspired oxygen faction (PaO2/FiO2) ratio and radiologic evolution in patients with severe SARS COV2 pneumonia.

Measure: Respiratory changes

Time: 30 days

Other Outcomes

Description: Stablish the nosocomial infections in subjects with or without AKI

Measure: Nosocomial Infections

Time: 30 days
98 COVID-19 : Transcutaneous pO2 and pCO2 as Predictive Factors for Acute Respiratory Destress Syndrome in Patients Affected With SARS-Cov-2

The first case of a person infected with SARS-Cov-2 virus can be tracked back on November the 17th, 2019, in China. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 outbreak a pandemic. On April 13, COVID-19 is affecting 210 countries and territories worldwide, about 2 million positive cases have been officially declared along with 115.000 deaths. The real number of infected and deaths is scarily higher, considering that up to 65% people are asymptomatic and thus, not tested. The percentage of patients with COVID-19 needed for intensive care unit (ICU) varied from 5 to 32% in Wuhan, China. It was up to 9% in Lombardy, Italy. According to available data from Lombardy, 99% of patients admitted to the ICU needed respiratory support (88% invasive ventilation, 11% non invasive ventilation). The aim of the present investigation is to test the hypothesis whether transcutaneous partial O2 and CO2 pressures may be reliable predictive factors for acute respiratory distress syndrome (ARDS) development in hospitalized clinically stable COVID-19 positive patients and to clarify the role of the Angiotensin Converting Enzyme 2 (ACE2) and its final product, angiotensin 2 (Ang II) in the pathogenesis of this systemic disease. We also aim to test the hypothesis that plasma concentration of Clara Cell protein (CC16) and surfactant protein D (SPD), which are a biomarkers of acute lung injury, are severely decreased in COVID-19 positive patients and the plasma concentration is related to the severity of lung injury.

NCT04524156
Conditions
  1. COVID
  2. Acute Respiratory Distress Syndrome
  3. Endothelial Dysfunction
Interventions
  1. Other: Physiology
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: To test the prognostic utility of TcpO2 and TcpCO2 for the prediction of COVID19 related lung injury and acute respiratory distress syndrome (ARDS) compared to finger oxygen saturation.

Measure: Transcutaneous pO2 and pCO2 as predictive factors for respiratory deterioration

Time: 6 months

Description: To test the prognostic utility of CC16 and SPD in patients with COVID19-related acute lung injury

Measure: Pneumoproteins CC16 and SDP as predictive factors for respiratory deterioration

Time: 6 months

Description: To test the hypothesis that plasma concentration of ACE2, AngII, Ang 1-7 and Ang 1-9 are profoundly impaired in COVID-19 and may be predictive factors of clinical deterioration

Measure: Diagnostic and prognostic utility of plasma concentration of ACE2, Ang II, Ang 1-7, Ang 1-9 in COVID-19

Time: 6 months
99 A Phase 2a, Open-Label, Single-Arm Study to Investigate the Safety and Efficacy of ATI-450 for the Maintenance of Remission in Patients With Cryopyrin-Associated Periodic Syndrome (CAPS) Previously Managed With Anti-IL-1 Therapy

This is a Phase 2 study to investigate the safety and efficacy of ATI-450 for the Maintenance of Remission in Patients with Cryopyrin-Associated Periodic Syndrome (CAPS) Previously Managed with Anti-IL-1 Therapy.

NCT04524858
Conditions
  1. Cryopyrin-Associated Periodic Syndrome
Interventions
  1. Drug: ATI-450
MeSH:Cryopyrin-Associated Periodic Syndromes Syndrome

Primary Outcomes

Description: Adverse Events (AEs) will be coded with the Medical Dictionary for Regulatory Activities (MedDRA). AEs will be presented by system organ class and preferred term in frequency tables.

Measure: Assess the safety and tolerability of ATI-450 to maintain remission in patients with CAPS previously managed with anti-IL-1 therapy: Adverse Events (AEs)

Time: Baseline to week 12

Secondary Outcomes

Description: Remission is defined as a high sensitivity C-reactive protein (hsCRP) within normal range (≤10 mg/L).

Measure: Total Number of participants who maintain disease remission (hsCRP)

Time: Baseline to week 12

Description: Remission is defined as a serum amyloid A (SAA) value within the normal range (≤10 mg/L).

Measure: Total Number of participants who maintain disease remission (SAA)

Time: Baseline to week 12

Description: Remission is defined as a Physician Global Assessment (PGA) score of absent or minimal. The Physician's Global Assessment of Autoinflammatory Disease Activity (PGA) is a measure to be completed by the investigator or designee. The PGA uses a 5-point rating scale: absent, minimal, mild, moderate, and severe. The investigator will select a rating based on the patient's current disease activity at the time of the visit. Lower PGA scores represent better outcomes.

Measure: Total number of participants who maintain disease remission (PGA)

Time: Baseline to week 12

Description: Relapse is defined as a two-point worsening on the PGA scale. The Physician's Global Assessment of Autoinflammatory Disease Activity (PGA) is a measure to be completed by the investigator or designee. The PGA uses a 5-point rating scale: absent, minimal, mild, moderate, and severe. The investigator will select a rating based on the patient's current disease activity at the time of the visit. Lower PGA scores represent better outcomes.

Measure: Time to relapse

Time: Baseline to week 12

Description: Re-emergence is defined as a daily Key Symptom Score (KSS) ≥ 3 points higher than baseline for at least 2 consecutive days. The KSS is derived from the patient-administered DHAF, and is the average on a 0 to 10 scale (0 = None, 10 = Very Severe) of 5 separate scales - rash, feeling of fever and chills, joint pain, eye redness and pain, and fatigue. Lower KSS scores represent better outcomes.

Measure: Total number of participants who experience re-emergence of disease symptoms after discontinuation of ATI-450

Time: Follow-up day 1 to follow-up day 7

Description: Key Symptom Score (KSS). The KSS is derived from the patient-administered DHAF, and is the average on a 0 to 10 scale (0 = None, 10 = Very Severe) of 5 separate scales - rash, feeling of fever and chills, joint pain, eye redness and pain, and fatigue. Lower KSS scores represent better outcomes.

Measure: Total number of participants with a mean KSS no more than 2 points higher than baseline for at least 6 out of 8 weeks during the treatment period

Time: Baseline to week 12

Description: Physician Global Assessment (PGA). The Physician's Global Assessment of Autoinflammatory Disease Activity (PGA) is a measure to be completed by the investigator or designee. The PGA uses a 5-point rating scale: absent, minimal, mild, moderate, and severe. The investigator will select a rating based on the patient's current disease activity at the time of the visit. Lower PGA scores represent better outcomes.

Measure: Change from baseline in PGA

Time: Baseline to week 12

Description: Key Symptom Score (KSS). The KSS is derived from the patient-administered DHAF, and is the average on a 0 to 10 scale (0 = None, 10 = Very Severe) of 5 separate scales - rash, feeling of fever and chills, joint pain, eye redness and pain, and fatigue. Lower KSS scores represent better outcomes.

Measure: Change from baseline in KSS

Time: Baseline to week 12

Description: C-reactive protein (CRP). CRP values ≤10 mg/L are considered normal range.

Measure: Change from baseline in CRP

Time: Baseline to week 12

Description: serum amyloid A (SAA). SAA values ≤10 mg/L are considered normal range.

Measure: Change from baseline in SAA

Time: Baseline to week 12

Other Outcomes

Description: Exploratory endpoint to assess the change from baseline in serum cytokines IL-1β ATI-450 in patients with CAPS.

Measure: Change from baseline in serum cytokines IL-1β

Time: Baseline to week 12

Description: Exploratory endpoint to assess the change from baseline in serum cytokines IL-1α of ATI-450 in patients with CAPS.

Measure: Change from baseline in serum cytokines IL-1α

Time: Baseline to week 12

Description: Exploratory endpoint to assess the change from baseline in serum cytokines IL-6 of ATI-450 in patients with CAPS.

Measure: Change from baseline in serum cytokines IL-6

Time: Baseline to week 12

Description: Exploratory endpoint to assess the change from baseline in serum cytokines IL-18 of ATI-450 in patients with CAPS.

Measure: Change from baseline in serum cytokines IL-18

Time: Baseline to week 12

Description: Exploratory endpoint to assess the change from baseline in serum cytokines TNF-α of ATI-450 in patients with CAPS.

Measure: Change from baseline in serum cytokines TNF-α

Time: Baseline to week 12
100 Phase I/IIA Study of Descartes-30 in Acute Respiratory Distress Syndrome

Emergency study to test the safety of Descartes-30 cells in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) AND COVID-19

NCT04524962
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Covid19
Interventions
  1. Biological: Descartes 30
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Measure: To assess the safety of Descartes-30 in patients with moderate-to-severe ARDS.

Time: 2 years
101 Defibrotide Therapy for SARS-CoV2 Acute Respiratory Distress Syndrome (ARDS)

This clinical trial will enroll participants that have pneumonia caused by the COVID-19 virus. During the study patients will receive 7 to up to 14 days of defibrotide. After completing the treatment, participants will have 30 day follow-up check-up to assess for adverse events and clinical status. This final assessment can be done virtually, by telephone or electronically (email) if the patient cannot be contacted by phone. No in-person visit is required. The hypothesis of this trial is that defibrotide therapy given to patients with severe SARS-CoV2 ARDS will be safe and associated with improved overall survival, within 28 days of therapy initiation.

NCT04530604
Conditions
  1. COVID
  2. Sars-CoV2
  3. COVID-19
  4. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Defibrotide
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Major hemorrhagic complications will be based on the International Society on Thrombosis and Haemostasis Bleeding scale. Fatal Bleeding, and/or Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or Bleeding associated with a decline in hemoglobin level of > 2.0 g/dl, leading to transfusion of two or more units of whole blood or red cells. In addition, symptomatic alveolar hemorrhage, macroscopic hematuria, uncontrolled menorrhagia or epistaxis or bleeding from any wound site would also be considered a major hemorrhagic event.

Measure: Number of major hemorrhagic complications within 14 days of initiation of treatment

Time: 14 days

Secondary Outcomes

Description: Proportion of the twelve patients who are alive at day 28 after starting treatment.

Measure: Overall survival

Time: 28 days

Description: Proportion of the twelve patients who are alive at Day 14 after starting treatment.

Measure: Overall survival

Time: 14 days

Description: Day 14 ventilator-free survival will be summarized by the proportion of the twelve patients who are both alive and not using a ventilator at Day 14 after starting treatment.

Measure: Ventilator free survival

Time: 14 days

Measure: Number of ventilator free days within 14 days of study entry

Time: 14 days

Description: Improvement in oxygenation defined as an increase in atio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) of 50 (or greater) compared to the nadir of PaO2/FiO2.

Measure: The time to improvement in oxygenation

Time: up to 14 days

Description: Ordinal scale: Ambulatory (1) - No limitation of activities (2) - Limitations of activities Hospitalized: (3) no oxygen therapy (4) oxygen by mask or nasal prongs Hospitalized: (5) Non-invasive ventilation or high-flow oxygen (6) Intubation and mechanical ventilation (7) Mechanical ventilation plus additional organs support-pressors, renal replacement therapy (RRT), Extracorporeal membrane oxygenation (ECMO) Dead: (8) Death

Measure: Mean change in the WHO COVID-19 Ordinal Scale during therapy

Time: up to 14 days
102 A Study of Brexanolone for Acute Respiratory Distress Syndrome Due to COVID-19

The purpose of this study is to evaluate the efficacy and safety of brexanolone in participants on ventilator support for acute respiratory distress syndrome (ARDS) due to COVID-19.

NCT04537806
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Drug: Brexanolone
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Respiratory failure is defined based on resource utilization, requiring at least one of the following: endotracheal intubation and mechanical ventilation; oxygen delivered by high-flow nasal cannula; noninvasive positive pressure ventilation or extracorporeal membrane oxygenation (ECMO).

Measure: Percentage of Participants Who are Alive and Free of Respiratory Failure at Day 28

Time: Day 28

Secondary Outcomes

Measure: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)

Time: Up to Day 28

Measure: All-cause Mortality Through Day 28

Time: Up to Day 28
103 A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Orally Administered Dapansutrile Capsules for the Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome

The purpose of this study is to assess the safety and efficacy of orally administered NLRP3 inhibitor, dapansutrile, for the treatment of moderate COVID-19 symptoms and early cytokine release syndrome (CRS) in an ambulatory, at-home setting. Coronavirus disease 2019 (COVID-19) is caused by infection from a new strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by fever, cough and shortness of breath, which in certain patients can lead to systemic organ failure and mortality. The data show that SARS-CoV-2 activates the innate immune signaling sensor NLRP3. Activation of NLRP3 initiates the cytokine release syndrome (CRS), which includes the production of primary cytokine, IL-1, triggering an intense inflammatory response that is prevalent in symptomatic COVID-19 patients. When CRS advances further to a fulminant 'cytokine storm', the data show that respiratory distress syndrome and multiple-organ failure take place. As a specific inhibitor of NLRP3, dapansutrile may reduce or prevent the hyperinflammation associated with CRS by inhibiting the production of IL-1β early to arrest the progression to a severe 'cytokine storm.' The end result would be a reduction in the need for COVID-19 patients to receive intensive medical treatment, allowing for fewer hospitalizations, administration of mechanical ventilation and deaths.

NCT04540120
Conditions
  1. Covid19
  2. Cytokine Release Syndrome
Interventions
  1. Drug: dapansutrile capsules
  2. Drug: placebo capsules
MeSH:Syndrome

Primary Outcomes

Description: Proportion of subjects with complete resolution of fever symptoms (feeling feverish, chills, shivering and/or sweating) and shortness of breath by Day 15

Measure: Proportion of subjects with complete resolution of fever symptoms and shortness of breath

Time: Day 15

Secondary Outcomes

Description: Evaluate the cumulative incidence of SAEs of dapansutrile relative to placebo

Measure: Cumulative incidence of SAEs

Time: Day 45

Description: Evaluate the cumulative incidence of Grade 3 and Grade 4 Adverse Events of dapansutrile relative to placebo

Measure: Cumulative incidence of Grade 3 and Grade 4 Adverse Events

Time: Day 45

Description: Evaluate the cumulative incidence of discontinuation or temporary suspension (for any reason) of dapansutrile relative to placebo

Measure: Discontinuation or temporary suspension of participation

Time: Day 45

Description: Evaluate changes in white cell count of dapansutrile relative to placebo over time

Measure: Changes in white cell count

Time: Day 8, Day 15

Description: Evaluate changes in hemoglobin of dapansutrile relative to placebo over time

Measure: Changes in hemoglobin

Time: Day 8, Day 15

Description: Evaluate changes in platelets of dapansutrile relative to placebo over time

Measure: Changes in platelets

Time: Day 8, Day 15

Description: Evaluate changes in creatinine of dapansutrile relative to placebo over time

Measure: Changes in creatinine

Time: Day 8, Day 15

Description: Evaluate changes in glucose of dapansutrile relative to placebo over time

Measure: Changes in glucose

Time: Day 8, Day 15

Description: Evaluate changes in total bilirubin of dapansutrile relative to placebo over time

Measure: Changes in total bilirubin

Time: Day 8, Day 15

Description: Evaluate changes in ALT of dapansutrile relative to placebo over time

Measure: Changes in ALT

Time: Day 8, Day 15

Description: Evaluate changes in AST of dapansutrile relative to placebo over time

Measure: Changes in AST

Time: Day 8, Day 15

Description: Evaluate changes in incidence of new infection that occurs during the study of dapansutrile relative to placebo

Measure: Incidence of new infection that occurs during the study

Time: Day 8, Day 15

Description: Evaluate changes in incidence of opportunistic infections of dapansutrile relative to placebo

Measure: Incidence of opportunistic infections

Time: Day 8, Day 15

Description: Proportion of subjects who experience clinical resolution of fever symptoms and shortness of breath

Measure: Complete resolution of fever symptoms and shortness of breath

Time: Day 8, Day 29 and Day 45

Description: Time to clinical improvement in fever symptoms and shortness of breath

Measure: Time to clinical improvement

Time: Baseline/Day 1 to Day 15

Description: Time to sustained absence of fever, defined as at least 2 days since last temperature measurement of ≥ 38˚C (100.4°F)

Measure: Time to sustained absence of fever

Time: Baseline/Day 1 to Day 15

Description: Proportion of subjects who experience clinical improvement in symptoms relevant to COVID 19 (e.g., cough, diarrhea, vomiting)

Measure: Clinical improvement in symptoms relevant to COVID 19

Time: Day 15

Description: Incidence of subjects meeting the composite endpoint of subjects requiring hospitalization (hospitalization is defined as ≥ 24 hours of acute care), supplemental oxygen, mechanical ventilation, or who die

Measure: Incidence of composite endpoint of hospitalization, supplemental oxygen, mechanical ventilation, or death

Time: Day 45

Description: Proportion of subjects who experience clinical improvement in symptoms by Day 15, defined as a reduction of two or more points on the WHO Ordinal Scale for Clinical Improvement (lowest score between Baseline Visit/Day 1 and Day 15)

Measure: Clinical improvement in symptoms

Time: Baseline/Day 1 to Day 15

Description: Improvement in oxygenation over the course of the study and maintenance of this effect

Measure: Improvement in oxygenation

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in AST

Measure: Change in ALT

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in AST

Measure: Change in AST

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in blood glucose

Measure: Change in blood glucose

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Erythrocyte Sedimentation Rate (ESR)

Measure: Change in Erythrocyte Sedimentation Rate (ESR)

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Hemoglobin A1c (HbA1C)

Measure: Change in Hemoglobin A1c (HbA1C)

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Lactate dehydrogenase (LDH)

Measure: Change in Lactate dehydrogenase (LDH)

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Lymphocyte, Absolute count

Measure: Change in Lymphocyte, Absolute count

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Monocyte, Absolute count

Measure: Change in Monocyte, Absolute count

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Neutrophils, Absolute count

Measure: Change in Neutrophils, Absolute count

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Eosinophil, Absolute count

Measure: Change in Eosinophil, Absolute count

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in CRP

Measure: Change in CRP

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in D-Dimer

Measure: Change in D-Dimer

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Ferritin

Measure: Change in Ferritin

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Fibrinogen

Measure: Change in Fibrinogen

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in Partial Thromboplastin Time (PTT) and International Normalized Ratio (INR)

Measure: Change in Partial Thromboplastin Time (PTT) and International Normalized Ratio (INR)

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in IL-1β

Measure: Change in IL-1β

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in IL-6

Measure: Change in IL-6

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in IL-18

Measure: Change in IL-18

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in granulocyte colony-stimulating factor (G-CSF)

Measure: Change in granulocyte colony-stimulating factor (G-CSF)

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in interferon-γ-induced protein 10 (IP-10)

Measure: Change in interferon-γ-induced protein 10 (IP-10)

Time: Baseline/Day 1 to Day 15

Description: Assess and compare change from Baseline in C3a

Measure: Change in C3a

Time: Baseline/Day 1 to Day 15
104 A Phase I Pilot Study of the Safety of Infusions of Allogeneic Human Cord Tissue Mesenchymal Stromal Cells in Children With Multisystem Inflammatory Syndrome in Children (MIS-C)

The purpose of this multi-site, pilot study is to test whether infusions of human cord tissue mesenchymal stromal cells (hCT-MSC) are safe in children with multi system inflammatory syndrome (MIS-C). We will also describe the symptom course and duration of this hyper-inflammatory syndrome in these patients. Six patients less than 21 years old with MIS-C that is refractory to intravenous immune globulin (IVIG) and/or steroids will be given intravenous infusions of hCT-MSCs. Doses of 2x10^6 cells/kg (up to a maximum dose of 100x10^6 cells) will be given on days 1, 2, 3, +/-7 (day 7 is optional). Participants will be followed up to 90 days after administration for severe adverse events and survival. Safety will be evaluated through adverse event monitoring, clinical evaluations (i.e., vital signs, physical examinations), laboratory tests (i.e., hematology, serum chemistries, and urinalysis), and cardiac function (i.e., echocardiogram, ECG) from the signing of informed consent and throughout the patient's participation in this treatment protocol.

NCT04549285
Conditions
  1. Multisystem Inflammatory Syndrome in Children
Interventions
  1. Biological: Human Cord Tissue Mesenchymal Stromal Cells (hCT-MSCs)
MeSH:Syndrome

Primary Outcomes

Description: Incidence of infusion reactions

Measure: Safety of the Investigational Product, hCT-MSCs, infusion reactions

Time: 2 days post infusion

Description: Incidence of later reactions attributed to the investigational product

Measure: Safety of the Investigational Product, hCT-MSCs, related adverse events

Time: 90 days post initial infusion

Description: Incidence of formation of new anti-HLA antibodies post infusion as compared to pre-infusion levels.

Measure: Safety of the Investigational Product, hCT-MSCs, anti-HLA antibodies

Time: from first dose of MSCs to 28 days after first dose

Secondary Outcomes

Description: Survival rate at 28 days after the first dose of MSCs

Measure: Survival

Time: from first dose of MSCs to 28 days after first dose

Description: Description of duration of inotrope support after the first dose of MSCs

Measure: Inotrope support

Time: from first dose of MSCs to 90 days after first dose

Description: Description of number of days to hospital discharge to home

Measure: Hospital Discharge

Time: from first dose of MSCs to 90 days after first dose

Description: Description of Duration of ICU stay

Measure: Duration of ICU stay

Time: from first dose of MSCs to 90 days after first dose

Description: Incidence of cardiac abnormalities at day 28, defined as persistent abnormalities in ECG, Echo, or biochemical markers (pro-BNP, troponin).

Measure: cardiac abnormalities

Time: from first dose of MSCs to 28 days after first dose
105 A Randomized, Double-blind, Dose-ranging, Placebo Controlled, Phase 2a Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19 (INTEGRIS-ARDS)

Evaluation of the safety, tolerability, and pharmacokinetics of PLN-74809 in participants with acute respiratory distress syndrome (ARDS) associated with at least severe COVID-19

NCT04565249
Conditions
  1. Acute Respiratory Distress Syndrome
  2. SARS-CoV-2
Interventions
  1. Drug: PLN-74809
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: Number of participants with treatment-related adverse events and laboratory abnormalities, assessed by CTCAE V5.0

Time: Up to 90 days

Secondary Outcomes

Measure: Assessment of PLN-74809 plasma concentrations

Time: up to 14 days

Other Outcomes

Measure: Number of participants alive and free of invasive mechanical ventilation

Time: up to 28 days

Measure: Number of participants alive and discharged from hospital

Time: Up to 28 days

Measure: Number of participants alive and discharged from hospital

Time: Up to 90 days
106 Emergency Use Pilot Study of Cord Blood Derived Mesenchymal Stem Cells for Treatment of COVID-19 Related Acute Respiratory Distress Syndrome

This phase I trial investigates the side effects of cord blood-derived mesenchymal stem cells (MSC) in treating patients with COVID-19 infection (COVID-19)-related acute respiratory distress syndrome (ARDS). MSCs are a type of stem cell that can be taken from umbilical cord blood and grown into many different cell types that can be used to treat cancer and other diseases. The MSCs being used for infusion in this trial are collected from healthy, unrelated donors and are stored and grown in a laboratory. Giving MSC infusions may help control the symptoms of ARDS.

NCT04565665
Conditions
  1. COVID-19 Infection
  2. COVID-19-Associated Acute Respiratory Distress Syndrome
Interventions
  1. Other: Best Practice
  2. Biological: Mesenchymal Stem Cell
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Serious adverse events with be comprised of grade 3 or 4 graft versus host disease or death and will be estimated and reported overall and by group, along with 95% confidence intervals.

Measure: Incidence of composite serious adverse events (Pilot)

Time: Within 30 days of the first mesenchymal stem cell (MSC) infusion

Measure: Patients alive without grade 3, 4 infusional toxicity (Phase II)

Time: At day 30 post MSC infusion

Measure: Patients alive with grade 3 or 4 infusional toxicity (Phase II)

Time: At day 30 post MSC infusion

Measure: Patients not alive (Phase II)

Time: At day 30 post MSC infusion

Secondary Outcomes

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Proportion of successfully extubated patients who present intubated on ventilator support (Pilot)

Time: Up to day 30 post MSC infusion

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Rate of successful progression to intubation in patients who require supplemental oxygen but who are otherwise able to breathe without assistance (Pilot)

Time: Up to day 30 post MSC infusion

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Overall survival rate (Pilot)

Time: At day 30 post MSC infusion

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Survival rate in patients who present intubated on ventilator support (Pilot)

Time: At day 30 post MSC infusion

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Survival rate in patients who require supplemental oxygen but who are otherwise able to breathe without assistance (Pilot)

Time: At day 30 post MSC infusion

Description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Measure: Determine the treatment effect on clinical parameters, oxygenation and respiratory parameters

Time: Up to day 30 post MSC infusion

Measure: Hospitalization stay (Pilot)

Time: Up to day 30 post MSC infusion

Measure: Intensive care unit stay (Pilot)

Time: Up to day 30 post MSC infusion

Description: All grades of infusion-related adverse events will be summarized by grade and type.

Measure: Incidence of infusion-related adverse events (Pilot)

Time: Up to day 30 post MSC infusion

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An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.

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