Name (Synonyms) | Correlation | |
---|---|---|
drug82 | Azithromycin Wiki | 0.23 |
drug87 | Azithromycin Tablets Wiki | 0.22 |
drug708 | Ruxolitinib Oral Tablet Wiki | 0.22 |
drug184 | ChAdOx1 MERS Wiki | 0.22 |
drug554 | Nitric Oxide Gas Wiki | 0.18 |
drug821 | Tele-medicine platform Wiki | 0.15 |
drug894 | Verapamil Wiki | 0.15 |
drug610 | Phosphate buffered saline Placebo Wiki | 0.15 |
drug528 | NA (no intervention) Wiki | 0.15 |
drug261 | Dexmedetomidine Injectable Product Wiki | 0.15 |
drug389 | Hydroxychloroquine and Azithromycin Wiki | 0.15 |
drug194 | Chloroquine diphosphate Wiki | 0.15 |
drug794 | Streptokinase Wiki | 0.15 |
drug452 | Ketamine Wiki | 0.15 |
drug566 | Normal Saline Infusion + Maximal intensive care Wiki | 0.15 |
drug448 | Ivermectin plus Nitazoxanide Wiki | 0.15 |
drug259 | Dexamethasone and Hydroxychloroquine Wiki | 0.15 |
drug387 | Hydroxychloroquine Sulfate and Azithromycin Wiki | 0.15 |
drug89 | BAT Wiki | 0.15 |
drug1027 | standard procedure Wiki | 0.15 |
drug531 | NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells Wiki | 0.15 |
drug12 | 2: No instruction regarding positioning Wiki | 0.15 |
drug890 | Valsartan (Diovan) Wiki | 0.15 |
drug537 | Naltrexone Wiki | 0.15 |
drug693 | Remestemcel-L Wiki | 0.15 |
drug617 | Placebo (Plasma-Lyte 148) Wiki | 0.15 |
drug629 | Placebo solution Wiki | 0.15 |
drug143 | CAStem Wiki | 0.15 |
drug877 | Umbilical cord Wharton's jelly-derived human Wiki | 0.15 |
drug43 | Aluminum hydroxide adjuvant (Alhydrogel®) Wiki | 0.15 |
drug61 | Ascorbic Acid and Folic Acid Wiki | 0.15 |
drug81 | Azinc Wiki | 0.15 |
drug323 | Gimsilumab Wiki | 0.15 |
drug951 | eculizumab Wiki | 0.15 |
drug191 | Chloroquine Diphosphate Wiki | 0.15 |
drug623 | Placebo for Hydroxychloroquine Wiki | 0.15 |
drug938 | care modalities Wiki | 0.15 |
drug219 | Continuous renal replacement therapy Wiki | 0.15 |
drug508 | Methylprednisolone Sodium Succinate Wiki | 0.15 |
drug90 | BAT + Calcifediol Wiki | 0.15 |
drug415 | Immunological profiling Wiki | 0.15 |
drug682 | Ravulizumab Wiki | 0.15 |
drug622 | Placebo for Azithromycin Wiki | 0.15 |
drug121 | Biological test Wiki | 0.15 |
drug485 | MRx-4DP0004 Wiki | 0.15 |
drug78 | Aviptadil by intravenous infusion + maximal intensive care Wiki | 0.15 |
drug822 | Teleconsultation either by phone or by computer consultation Wiki | 0.15 |
drug8 | 1: Prone positioning Wiki | 0.15 |
drug33 | Aerosol-reducing Mask Wiki | 0.15 |
drug471 | Lopinavir / Ritonavir plus Ribavirin Wiki | 0.15 |
drug829 | Telmisartan 40mg Wiki | 0.15 |
drug44 | Amiodarone Wiki | 0.15 |
drug474 | Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki | 0.15 |
drug95 | BLD-2660 Wiki | 0.15 |
drug591 | PEEP trial Wiki | 0.15 |
drug41 | Alteplase 50 MG [Activase] Wiki | 0.15 |
drug103 | BVRS-GamVac Wiki | 0.15 |
drug388 | Hydroxychloroquine Sulfate and Folic Acid Wiki | 0.15 |
drug879 | Unfractionated heparin Wiki | 0.15 |
drug945 | consultation Wiki | 0.15 |
drug83 | Azithromycin (Azithro) Wiki | 0.15 |
drug764 | Standard Mask Wiki | 0.15 |
drug535 | NaCl 0.9% Wiki | 0.15 |
drug825 | Telephone survey Wiki | 0.15 |
drug814 | TCM prescriptions Wiki | 0.15 |
drug104 | BVRS-GamVac-Combi Wiki | 0.15 |
drug791 | Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki | 0.15 |
drug114 | Best Supportive Care Wiki | 0.15 |
drug355 | Human immunoglobulin Wiki | 0.15 |
drug536 | Nafamostat Mesilate Wiki | 0.15 |
drug356 | Human umbilical cord derived CD362 enriched MSCs Wiki | 0.15 |
drug40 | Alteplase 100 MG [Activase] Wiki | 0.15 |
drug964 | hydroxychloroquine sulfate 200 MG Wiki | 0.15 |
drug445 | Isotretinoin Only Product in Oral Dose Form Wiki | 0.15 |
drug685 | Recombinant S protein SARS vaccine Wiki | 0.15 |
drug375 | Hydroxychloroquine Sulfate Wiki | 0.15 |
drug1003 | placebo Wiki | 0.12 |
drug854 | Tocilizumab Wiki | 0.12 |
drug750 | Single Dose of Hydroxychloroquine Wiki | 0.11 |
drug107 | Baricitinib Wiki | 0.11 |
drug946 | convalescent plasma Wiki | 0.11 |
drug828 | Telmisartan Wiki | 0.11 |
drug995 | observational Wiki | 0.11 |
drug268 | Dornase Alfa Inhalation Solution [Pulmozyme] Wiki | 0.11 |
drug762 | Standard Care Wiki | 0.11 |
drug656 | Prone positioning Wiki | 0.11 |
drug748 | Siltuximab Wiki | 0.11 |
drug644 | Povidone-Iodine Nasal Spray and Gargle Wiki | 0.11 |
drug1023 | standard care Wiki | 0.11 |
drug627 | Placebo oral tablet Wiki | 0.10 |
drug360 | Hydroxychloroquine Wiki | 0.10 |
drug616 | Placebo Wiki | 0.10 |
drug361 | Hydroxychloroquine (HCQ) Wiki | 0.09 |
drug60 | Ascorbic Acid Wiki | 0.09 |
drug469 | Lopinavir / Ritonavir Wiki | 0.09 |
drug428 | Interferon Beta-1A Wiki | 0.09 |
drug936 | blood sampling Wiki | 0.08 |
drug883 | Usual Care Wiki | 0.08 |
drug46 | Anakinra Wiki | 0.06 |
drug507 | Methylprednisolone Wiki | 0.05 |
drug775 | Standard of care Wiki | 0.05 |
drug632 | Placebos Wiki | 0.04 |
Name (Synonyms) | Correlation | |
---|---|---|
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.47 |
D055371 | Acute Lung Injury NIH | 0.47 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.43 |
D055370 | Lung Injury NIH | 0.24 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.24 |
D018352 | Coronavirus Infections NIH | 0.22 |
D054143 | Heart Failure, Systolic NIH | 0.15 |
D000787 | Angina Pectoris NIH | 0.15 |
D009102 | Multiple Organ Failure NIH | 0.15 |
D006333 | Heart Failure NIH | 0.15 |
D003327 | Coronary Disease NIH | 0.15 |
D000071257 | Emergence Delirium NIH | 0.15 |
D007249 | Inflammation NIH | 0.14 |
D054058 | Acute Coronary Syndrome NIH | 0.11 |
D003693 | Delirium NIH | 0.11 |
D003324 | Coronary Artery Disease NIH | 0.11 |
D011014 | Pneumonia NIH | 0.10 |
D011665 | Pulmonary Valve Insufficiency NIH | 0.09 |
D018746 | Systemic Inflammatory Response Syndrome NIH | 0.09 |
D009203 | Myocardial Ischemia NIH | 0.09 |
D011024 | Pneumonia, Viral NIH | 0.08 |
D058186 | Acute Kidney Injury NIH | 0.07 |
D007251 | Influenza, Human NIH | 0.06 |
D002318 | Cardiovascular Diseases NIH | 0.05 |
D014777 | Virus Diseases NIH | 0.03 |
D007239 | Infection NIH | 0.03 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0010444 | Pulmonary insufficiency HPO | 0.15 |
HP:0002791 | Hypoventilation HPO | 0.15 |
HP:0002090 | Pneumonia HPO | 0.02 |
There are 42 clinical trials
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
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.
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.
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.
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.
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 7Description: Incidence of SAEs
Measure: Incidence of Serious Adverse Events (SAEs) Time: 28 daysDescription: SOFA score is a measure of organ failure
Measure: Sequential Organ Failure Assessment (SOFA) score Time: Days 4, 7 and 14Description: Crs is a physiological measure of pulmonary function in ARDS
Measure: Respiratory compliance (Crs) Time: Days 4, 7 and 14Description: 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 14This 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
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.
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 vaccinationDescription: 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 monthsBackground: 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.
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 daysDescription: 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 daysDescription: 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 daysDescription: 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 recruitmentDescription: 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 recruitmentDescription: number of patients who required tracheostomy
Measure: Tracheostomy rate Time: During ICU stay up to one month after the start of recruitmentThe 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.
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 daysDescription: 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 daysDescription: 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 daysDescription: 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 90Description: 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 valuesThe 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.
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 daysDescription: 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 daysDescription: 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 daysDescription: 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 90Description: 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 28A 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
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 vaccinationDescription: 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 regimenThe 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).
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 treatmentDescription: Composite outcome in which: Death=0, Days of treatment =1
Measure: SARS-free days at 28 days Time: 28 daysDescription: Composite outcome in which: Death=0, Days of treatment =1
Measure: SARS -free days at 90 days Time: 90 daysDescription: Incidence
Measure: Renal Replacement Therapy Time: 28 daysDescription: Incidence
Measure: Liver Failure Time: 28 daysDescription: Incidence of patients requiring VA-ECMO, LVAD, IABP
Measure: Mechanical Support of Circulation Time: 28 daysDescription: In ambient air if possible
Measure: PaO2/FiO2 ratio in ambient air Time: daily for 28 daysCurrently, the growing epidemic of a new coronavirus infectious disease (Covid-19) is wreaking havoc worldwide, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a RNA virus that display high similarity in both genomic and proteomic profiling with SARS-CoV that first emerged in humans in 2003 in China. Therefore, preventing and controlling the pandemic occurrences are extremely urgent as a global top priority. Due to the lack of effective antiviral drugs, patients may be treated by only addressing their symptoms such as reducing fever. Clinical autopsies from SARS-CoV-infected patients demonstrated that there were major pathological changes in the lungs, immune organs, and small systemic blood vessels with vasculitis. However, the detection of SARS-CoV were primarily found in the lung and trachea/bronchus, but was undetectable in spleen, lymph nodes, bone marrow, heart and aorta, highlighting the overreaction of immune responses induced by viral infection were really harmful, resulting in the pathogenesis of lungs, immune organs, and small systemic blood vessels. To this respect, immune modulation strategy may be potentially beneficial to enhance anti-viral immunity and efficiently reduce the viral load, improve clinical outcomes, expedite the patient recovery, and decline the rate of mortality in patients after being infected with SARS-CoV-2. Tianhe Stem Cell Biotechnologies Inc. has developed a novel globally-patented Stem Cell Educator (SCE) technology designed to reverse the autoimmune response in Type 1 diabetes (T1D), Alopecia Areata (AA) and other autoimmune diseases. SCE therapy uses human multipotent cord blood stem cells (CB-SC) from human cord blood. Their properties distinguish CB-SC from other known stem cell types, including mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC). Several clinical studies show that SCE therapy functions via CB-SC induction of immune tolerance in autoimmune T cells and restore immune balance and homeostasis in patients with T1D, AA and other inflammation-associated diseases. To correct the overreaction of overreaction of immune responses, the investigators plan to treat SARS-CoV-2 patients with Stem Cell Educator therapy.
Description: The feasibility will be evaluated by the number of Covid-19 patients who were unable to complete SCE Therapy.
Measure: Determine the number of Covid-19 patients who were unable to complete SCE Therapy Time: 4 weeksDescription: Measurements of immune markers' changes will be preformed by flow cytometry such as activated T cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.
Measure: Examine the percentage of activated T cells after SCE therapy by flow cytometry Time: 4 weeksDescription: Measurements of immune marker's changes will be preformed by flow cytometry such as the percentage of Th17 cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.
Measure: Assess the percentage of Th17 cells after SCE therapy by flow cytometry Time: 4 weeksDescription: Patients will be monitored for their chest imaging every 3 - 5 days for 4 weeks after receiving SCE therapy.
Measure: Chest imaging changes by computed tomography (CT) scan of the chest Time: 4 weeksDescription: To determine the viral load by real time RT-PCR, samples of blood, sputum, nose / throat swab will be collected from patients during the follow-up studies after receiving SCE therapy.
Measure: Quantification of the SARS-CoV-2 viral load by real time RT-PCR Time: 4 weeksSevere 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
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 hoursDescription: 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 daysDescription: 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 daysDescription: Proportion of patients surviving at 28 days within each group and comparison between groups.
Measure: Survival at 28 days from enrollment Time: 28 daysDescription: Proportion of patients surviving at 90 days within each group and comparison between groups.
Measure: Survival at 90 days from enrollment Time: 90 daysDescription: Expressed as PaO2/FiO2 ratio within each group and comparison between groups.
Measure: Daily oxygenation in the two groups until day 28 Time: 28 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Average days without need for mechanical ventilation within each group and comparison between groups.
Measure: Ventilator-free day at 28 days Time: 28 daysDescription: 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 daysDescription: Average days out of ICU within each group and comparison between groups.
Measure: ICU-free days at 28 days Time: 28 daysDescription: Average days of ICU admission within each group and comparison between groups.
Measure: ICU length of stay Time: 90 daysEvaluation of the efficacy and safety of TCM differential treatment of COVID-19 in Jiangsu Province based on a prospective multicenter cohort study.
Description: disappearance of fever, cough and shortness of breath/ the rate of complete relief /.
Measure: The relief / disappearance rate of main symptoms Time: 9dayDescription: with reference to the "pneumonia chest X-ray absorption Evaluation scale" developed by Renyi Yin et al, the final absorption judgment will be used to evaluate the chest CT absorption of patients with pneumonia, which is divided into four levels according to the degree of absorption: complete absorption, majority absorption, partial absorption and no absorption.
Measure: Chest CT absorption Time: 9dayDescription: detection negative rat of nasopharyngeal swab, conjunctival sac secretion virus nucleic acid e
Measure: Virus antigen negative conversion rate Time: 9dayDescription: the average time it takes for the clinical curative effect to reach the effective standard. Median response time: the average time it takes for 50% of patients to reach the effective standard.
Measure: Clinical effective time: the average effective time Time: 9dayDescription: the number of severe and critical cases occurred after the start of intervention.
Measure: The number of severe and critical conversion cases Time: 9dayDescription: defined as complications during isolation and hospitalization due to pneumonia infected by novel coronavirus, including bacterial infection, aggravation of underlying diseases, etc
Measure: Incidence of complications Time: 9dayDescription: According to the Traditional Chinese Medicine symptom score scale, the change of symptom score before and after treatment was observed.The highest score was 92 points, and the lowest was 23 points. The higher the score, the more severe the symptoms.
Measure: Traditional Chinese Medicine Syndrome Score Time: 9dayDescription: Changes in c-reactive protein.
Measure: CRP changes Time: 9dayDescription: Changes in erythrocyte sedimentation rate.
Measure: ESR changes Time: 9dayDescription: Changes in procalcitonin.
Measure: PCTchanges Time: 9dayDescription: Changes of CD4+ and CD8+
Measure: The index of T cell subsets changed Time: 9daySome 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.
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 daysDescription: Measured in days
Measure: Duration of hospitalization Time: Up to 28 daysDescription: 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 daysDescription: Blood routine test
Measure: Change from baseline in white blood cell and differential count Time: Day 1 through Day 28Description: Oropharyngeal or anal swabs
Measure: Time to first negative in 2019 novel Corona virus RT-PCR test Time: Up to 28 daysDescription: Date and cause of death (if applicable).
Measure: All-cause mortality Time: up to 12 weeksDescription: Serum hsCRP
Measure: Change from baseline in hsCRP Time: Day 1 through Day 28Description: 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 28Description: 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)Novel Corona Virus (COVID-19) is known to cause Acute Lung Injury/Acute Respiratory Distress Syndrome, that results in death of approximately 80% of those who develop ARDS, despite intensive care and mechanical ventilation. Patients with COVID-19 induced Acute Respiratory Distress Syndrome who are admitted for intensive care including endotracheal intubation and mechanical ventilation will be treated with Aviptadil, a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP) plus maximal intensive care vs. placebo + maximal intensive care. Patients will be randomized to intravenous Aviptadil will receive escalating doses from 50 -150 pmol/kg/hr over 12 hours.
Description: Mortality
Measure: Mortality Time: 5 Days with followup through 30 daysDescription: Index of Respiratory Distress
Measure: PaO2:FiO2 ratio Time: 5 Days with followup through the end of telemetry monitoringDescription: TNF alpha levels as measured in hospital laboratory
Measure: TNF alpha Time: 5 DaysDescription: Multi-system organ failure free days
Measure: Multi-system organ failure free days Time: 5 days with followup through 30 daysThe study aims to investigate organ dysfunction and biomarkers in patients with suspected or verified COVID-19 during intensive care at Uppsala University Hospital.
Description: KDIGO AKI score
Measure: Acute Kidney Injury Time: During Intensive Care, an estimated average of 10 days.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 daysDescription: Death within 1 year of ICU admission
Measure: 1 year mortality Time: 1 yearDescription: Development of Chronic Kidney Disease
Measure: Chronic Kidney Disease Time: 60 days and 1 year after ICU admissionDescription: Sequential Organ Failure Score as a continuous variable
Measure: SOFA-score Time: During Intensive Care, an estimated average of 10 days.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.
Description: proportion of deaths at day 28 between groups compared
Measure: Mortality rate reduction of 50% by day 28 Time: 28 days after randomizationDescription: number of deaths at days 7 and 14 between groups compared
Measure: Absolute mortality on days 7 and 14 Time: 7 and 14 days after first doseDescription: clinical status
Measure: Improvement in overall subject's clinical status assessed in standardized clinical questionnaires on days 14 and 28 Time: 14 and 28 days after first doseDescription: clinical status
Measure: Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization Time: during and after intervention, up to 28 daysDescription: supplemental oxygen
Measure: Duration of supplemental oxygen (if applicable) Time: during and after intervention, up to 28 daysDescription: mechanical ventilation
Measure: Duration of mechanical ventilation (if applicable) Time: during and after intervention, up to 28 daysDescription: hospitalization
Measure: Absolute duration of hospital stay in days Time: during and after intervention, up to 28 daysDescription: adverse events grade 3 and 4
Measure: Prevalence of grade 3 and 4 adverse events Time: during and after intervention, up to 28 daysDescription: adverse events
Measure: Prevalence of serious adverse events Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum creatinine compared to baseline
Measure: Change in serum creatinine level Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum troponin I compared to baseline
Measure: Change in serum troponin I level Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum aspartate aminotransferase compared to baseline
Measure: Change in serum aspartate aminotransferase level Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum aspartate aminotransferase compared to baseline
Measure: Change in serum CK-MB level Time: during and after intervention, up to 28 daysDescription: virus clearance from respiratory tract secretion
Measure: Change in detectable viral load in respiratory tract swabs Time: during and after intervention, up to 28 daysDescription: viremia in blood detected through RT-PCR
Measure: Viral concentration in blood samples Time: during and after intervention, up to 28 daysDescription: death
Measure: Absolute number of causes leading to participant death (if applicable) Time: during and after intervention, up to 28 daysCOVID-19 infection is overwhelming Italian healthcare. There is an urgent need for a solution to the lack of ICU beds and increasing deaths day after day. A recent retrospective Chinese paper (JAMA Intern Med, online March 13, 2020) showed impressive positive effect of methylprednisolone (MP) on survival of SARS-CoV-2 critically ill patients. We're routinely using MP for severe pneumonia-ARDS with acute respiratory failure with very good results. The main objective of this multi-centre observational trial is to evaluate the efficacy of low dose prolonged infusion of methylprednisolone (MP) for patients with severe acute respiratory syndrome.
Description: Death or ICU admission or Invasive mechanical ventilation (yes/not, at least one of three of the composite end-point)
Measure: Composite primary end-point Time: 28 daysDescription: Yes/no
Measure: death Time: 28 daysDescription: yes/no
Measure: Admission to ICU Time: 28 daysDescription: yes/no
Measure: Endotracheal intubation (invasive mechanical ventilation) Time: 28 daysDescription: mg/L
Measure: reduction of C-reactive protein or CRP Time: 14 days and 28 daysDescription: number of days free from mechanical ventilation (invasive or not)
Measure: Reduction of mechanical ventilation Time: 28 daysManagement 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.
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 monthsDescription: 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 monthsDescription: Will be the number of sessions per patient multiplied with the number of patients included
Measure: Number of consultations/sessions given Time: 6 monthsThis 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).
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 enrolmentDescription: 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 enrolmentDescription: 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 therapyDescription: PCR-confirmed COVID-19 diagnosis
Measure: Incidence rates of COVID-19 through study completion Time: 28 days from enrolmentA phase1/2, open label, dose escalation, safety and early efficacy study of CAStem for the treatment of severe COVID-19 associated with or without ARDS.
Description: Frequency of adverse reaction (AE) and severe adverse reaction (SAE) within 28 days after treatment
Measure: Adverse reaction (AE) and severe adverse reaction (SAE) Time: Within 28 days after treatmentDescription: Evaluation by chest CT
Measure: Changes of lung imaging examinations Time: Within 28 days after treatmentDescription: Marker for SARS-CoV-2
Measure: Time to SARS-CoV-2 RT-PCR negative Time: Within 28 days after treatmentDescription: The duration of a fever above 37.3 degrees Celsius
Measure: Duration of fever (Celsius) Time: Within 28 days after treatmentDescription: Marker for efficacy
Measure: Changes of blood oxygen (%) Time: Within 28 days after treatmentDescription: Marker for efficacy
Measure: Rate of all-cause mortality within 28 days Time: Within 28 days after treatmentDescription: Counts of lymphocyte in a litre (L) of blood
Measure: Lymphocyte count (*10^9/L) Time: Within 28 days after treatmentDescription: Alanine aminotransferase in unit (U)/litre(L)
Measure: Alanine aminotransferase (U/L) Time: Within 28 days after treatmentDescription: Creatinine in micromole (umol)/litre(L)
Measure: Creatinine (umol/L) Time: Within 28 days after treatmentDescription: Creatine kinase in U/L
Measure: Creatine kinase (U/L) Time: Within 28 days after treatmentDescription: C-reactive in microgram (mg)/litre(L)
Measure: C-reactive protein (mg/L) Time: Within 28 days after treatmentDescription: Procalcitonin in nanogram (ng)/litre(L)
Measure: Procalcitonin (ng/L) Time: Within 28 days after treatmentDescription: Lactate in millimole(mmol)/litre(L)
Measure: Lactate (mmol/L) Time: Within 28 days after treatmentDescription: IL-1beta in picogram(pg)/millilitre(mL)
Measure: IL-1beta (pg/mL) Time: Within 28 days after treatmentDescription: IL-2 in pg/mL
Measure: IL-2 (pg/mL) Time: Within 28 days after treatmentDescription: IL-6 in pg/mL
Measure: IL-6 (pg/mL) Time: Within 28 days after treatmentDescription: IL-8 in pg/mL
Measure: IL-8 (pg/mL) Time: Within 28 days after treatmentWhereas 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 60 patients, of whom 20 will be cell-treated while the remaining 40 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 Méary 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.
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.
Description: Presence of recovery of pneumonia characterized by cease of respiratory symptoms
Measure: Recovery of Pneumonia Time: 14 daysDescription: Increment or decrease in mg/ml of C-reactive protein
Measure: Response of C-reactive protein Time: 14 daysDescription: Increment or decrease in ng/ml of ferritin
Measure: Response of Ferritin Time: 14 daysDescription: Increment or decrease in mg/ml of D-dimer
Measure: Response of D-dimer Time: 14 daysDescription: Requirement of Intensive Care Unit on the patients under treatment
Measure: Rate of ICU admission Time: 14 daysDescription: Requirement of mechanical ventilation on the patients under treatment
Measure: Rate of mechanical ventilation Time: 14 daysDescription: Time since the diagnosis to the last follow up (recovery or death)
Measure: Overall Survival Time: 1 monthDescription: Rate of adverse events associated with ruxolitinib
Measure: Toxicity Rate Time: 1 monthRationale: 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.
Description: Death is defined as all-cause mortality
Measure: first occurrence of intensive care unit admission, mechanical ventilation or death Time: within 14 daysDescription: All-cause mortality; and time to all-cause mortality
Measure: Death Time: Within 14 days, 30 days, 90 days and at 1 yearDescription: Occurrence of mechanical ventilation and time to ventilation
Measure: Mechanical ventilation Time: within 14 daysDescription: Occurrence of ICU admission and time to admission
Measure: Intensive care unit admission Time: within 14 daysDescription: 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 daysThis is a double-blind, randomized, placebo-controlled clinical trial. A total of 210 individuals aged over 18 years old, without a diagnosis of severe respiratory disease, who came to the study site with clinical and radiological suspicion of SARS-CoV2, will be randomized into two treatment groups at a 1:1 ratio to receive a 5-day CQ diphosphate tablets or placebo (tablet without active ingredient produced with the same physical characteristics).
Description: Evaluate if CQ diphosphate prevents the onset of SARS in patients on intervention group through standardized questionnaires.
Measure: Proportion of patients with onset of severe acute respiratory syndrome (SARS) Time: 7 days after randomizationDescription: Mortality rate between intervention and placebo group on days 7, 14, and 28 after randomization
Measure: Mortality rate Time: after randomization, up to 28 daysDescription: Proportion of participants in need and duration of intensive care support after randomization
Measure: Number of participants in need of intensive care support Time: during and after intervention, up to 28 daysDescription: Viral load change in blood and oropharyngeal swab samples
Measure: Viral concentration Time: After randomization, up to 7 daysDescription: Incidence of serious adverse events during and after treatment
Measure: Cumulative incidence of serious adverse events Time: During and after intervention, up to 28 daysDescription: Incidence of grade 3 and 4 adverse events during and after treatment
Measure: Cumulative incidence of grade 3 and 4 adverse events Time: During and after intervention, up to 28 daysDescription: proportion of discontinuation or temporary suspension of treatment (for any reason)
Measure: Proportion of patients with discontinued treatment Time: after randomization, up to 28 daysDescription: proportion of patients with increased levels of troponin I
Measure: Incidence of cardiac lesions Time: after randomization, up to 120 daysDescription: proportion and magnitude of QTcF interval increases higher than 500ms
Measure: Incidence of cardiac disfunctions Time: after randomization, up to 120 daysDescription: Changes measured on day 120 will be compared to baseline, through spirometry.
Measure: Change in respiratory capacity Time: Day 120 after randomizationThis is a double-blind, randomized, placebo-controlled, phase IIb clinical trial to assess the efficacy and safety of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 420 individuals of both sexes, aged over 18 years old, with symptoms suggestive or confirmed diagnosis of severe acute respiratory syndrome (SARS), hospitalized at the Hospital and Pronto-Socorro Delphina Rinaldi Abdel Aziz (HPSDRAA), with clinical and radiological findings suggestive of SARS-CoV2 infection, will be randomized at a 1:1 ration to receive either MPS (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).
Description: Mortality rate on day 28, after randomization
Measure: Mortality rate at day 28 Time: on day 28, after randomizationDescription: Number of patients with diagnosis of early onset of SARS
Measure: Proportion of patients with SARS Time: after randomization, up to 7 days.Description: Proportion of patient that died on days 7, 14 and 28.
Measure: Mortality rate on days 7, 14 and 28 Time: after randomization, up to 28 days.Description: proportion of patients requiring orotracheal intubation
Measure: Incidence of orotracheal intubation Time: after randomization, up to 7 days.Description: Proportion of patients with oxygenation index (PaO2 / FiO2) < 100 in 7 days.
Measure: Change in oxygenation index Time: after randomization, up to 7 days.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.
Description: Mortality rate evaluated 28 days after randomization
Measure: Day-28 mortality Time: 28 days after randomizationDescription: 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 randomizationDescription: Mortality rate evaluated during Intensive care unit stay
Measure: Intensive Care Unit mortality Time: Up to 60 days after randomizationDescription: Mortality rate evaluated 60 days after randomization
Measure: Day-60 mortality Time: 60 days after randomizationDescription: Number of patients with pneumonia diagnosed during intensive care unit stay
Measure: Nosocomial pneumonia Time: Up to 60 days after randomizationDescription: Number of patients with bacteremia diagnosed during intensive care unit
Measure: Bacteremia Time: Up to 60 days after randomizationDescription: Placement of ECMO during intensive care unit stay
Measure: Extra corporeal membrane oxygenation (ECMO) Time: Up to 60days after randomizationDescription: Number of patients who underwent tracheostomy during intensive care unit stay
Measure: Tracheostomy Time: Up to 60 days after randomizationDescription: Number of Prone position session
Measure: Prone Position Time: Up to 60 days after randomizationAs 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.
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 daysDescription: 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 28Description: 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 28Description: Severity scoring of lung oedema on the chest radiograph
Measure: Radiological score Time: Days 1, 3, 7, 14, 21 and 28Description: Concentration in mg/L
Measure: Biological efficacy endpoints - C-reactive protein Time: Days 1, 3, 7, 14, 21 and 28Description: Concentration in microgram/L
Measure: Biological efficacy endpoints - Procalcitonin Time: Days 1, 3, 7, 14, 21 and 28Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes
Measure: Immunological profile Time: Up to 28 daysDescription: Use of corticosteroids, antiretroviral, chloroquine
Measure: Number of patients using other treatments for COVID-19 related ARDS Time: Up to 28 daysDescription: 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 daysDescription: 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 daysDescription: Medical research council sum score on awakening
Measure: Occurrence of critical illness neuromyopathy Time: Up to 28 daysDescription: 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 daysThe 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.
Description: no unit
Measure: Recruitment-to Inflation ratio (R/I ratio) Time: Day 1Description: no unit
Measure: Recruitment-to Inflation ratio (R/I ratio) Time: Day 5Description: no unit
Measure: Recruitment-to Inflation ratio (R/I ratio) Time: Day 10Description: Arterial blood gases
Measure: PaO2/FiO2 (mmHg) Time: Day 1Description: Arterial blood gases
Measure: PaO2/FiO2 (mmHg) Time: Day 5Description: Arterial blood gases
Measure: PaO2/FiO2 (mmHg) Time: Day 10Description: mL
Measure: Lung volume recruited (VRec) Time: Day 1Description: mL
Measure: Lung volume recruited (VRec) Time: Day 5Description: mL
Measure: Lung volume recruited (VRec) Time: Day 10Description: Obtained by inspiratory pause of 5 seconds
Measure: Plateau pressure (cm H2O) Time: Day 1Description: Obtained by inspiratory pause of 5 seconds
Measure: Plateau pressure (cm H2O) Time: Day 5Description: Obtained by inspiratory pause of 5 seconds
Measure: Plateau pressure (cm H2O) Time: Day 10Description: Obtained by expiratory pause of 5 seconds
Measure: PEEP total (cm H2O) Time: Day 1Description: Obtained by expiratory pause of 5 seconds
Measure: PEEP total (cm H2O) Time: Day 5Description: Obtained by expiratory pause of 5 seconds
Measure: PEEP total (cm H2O) Time: Day 10Description: 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 1Description: 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 5Description: 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 10Description: 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 1Description: 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 5Description: 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 10Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.
Description: Vital status at Day 43
Measure: Primary endpoint Time: 43 daysDescription: Incidence and duration of mechanical ventilation use during the study
Measure: Secondary endpoint Time: Day 43Description: Number of days in the ICU
Measure: Secondary endpoint Time: Day 43Description: Number of days of inpatient hospitalization
Measure: Secondary endpoint Time: Day 43This study plans to learn more about the effects of Dornase Alpha in COVID19 (coronavirus disease of 2019) patients, the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Dornase Alpha 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 Alpha 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.
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 7This protocol provides access to eculizumab treatment for participants with severe COVID-19.
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.
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 randomizationDescription: 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 randomizationDescription: 48 hour mortality for hospitalized patients
Measure: 48 hour in-hospital mortality Time: at 48 hours post randomizationDescription: 14 days mortality for hospitalized patients
Measure: 14 days in-hospital mortality Time: 14 days post randomizationDescription: 28 days mortality for hospitalized patients
Measure: 28 days in-hospital mortality Time: 28 days post randomizationDescription: 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 extubationDescription: 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 paralyticsDescription: 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)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
Description: (Presence/Absence) requirement of mechanical ventilation
Measure: Mechanical ventilation Time: expected within first three days (non conclusive due to lack of evidence yet)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 sedationThe 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 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.
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 positioningDescription: Changes in intrapulmonary shunt fraction
Measure: Intrapulmonary shunt Time: One hour before turning to prone or supine positioningDescription: Changes in the phase three slope of the volumetric capnogram
Measure: Volumetric capnography Time: One hour before turning to prone or supine positioningIt 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.
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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: every 24 hours fibrinogen value in mg/dl
Measure: Evaluation of known adverse events related to the use of the drug - fibrinogen Time: 15 daysDescription: every 24 hours transaminases value in U/L
Measure: Evaluation of known adverse events related to the use of the drug - transaminases Time: 15 daysDescription: every 24 hours aPTT value in seconds
Measure: Evaluation of known adverse events related to the use of the drug - aPTT Time: 15 daysDescription: every 24 hours INR value in %
Measure: Evaluation of known adverse events related to the use of the drug - INR Time: 15 daysDescription: every 24 hours glycemia value in mg/dl
Measure: Evaluation of known adverse events related to the use of the drug - glycemia Time: 15 daysDescription: 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 daysDescription: Total leucocyte as CBC x10e)/L
Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes count Time: 15 daysDescription: formula % on total leucocyte
Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes formula Time: 15 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Number of AE grade 1 to 4
Measure: Monitoring incidence of treatment Emergent Adverse Events of ruxolitinib therapy Time: 15 daysIdeal 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.
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 monthDescription: 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 monthDescription: 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 monthDescription: 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 monthDescription: Count of participants who die from COVID-19
Measure: Mortality Time: up to 1 month post hospital dischargeDescription: Length of hospital stay in days
Measure: Length of hospital stay Time: up to 1 monthDescription: Count of patients admitted to the ICU at any time during index hospitalization
Measure: Intensive Care Unit (ICU) admission Time: up to 1 monthDescription: Length of ICU stay in days
Measure: Intensive Care Unit (ICU) duration Time: up to 1 monthDescription: Count of participants requiring intubation
Measure: Intubation Time: up to 1 monthDescription: Length of intubation, measured in days
Measure: Intubation duration Time: up to 1 monthDescription: Time measured in days from hospital admission to determination patient is stable for discharge
Measure: Time until recovery Time: up to 1 monthThe 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).
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.
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.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.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.