Acute Respiratory Distress Syndrome Clinical Trial
Official title:
Mesenchymal Stromal Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome
Verified date | April 2022 |
Source | Icahn School of Medicine at Mount Sinai |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 223 |
Est. completion date | January 2, 2022 |
Est. primary completion date | January 14, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria - 18 years or older - Patient has SARS-CoV-2 (COVID-19) confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay or other diagnostic test - Patient requiring mechanical ventilatory support with moderate to severe ARDS as determined by the following criteria (adapted from the Berlin criteria) - Bilateral opacities must be present on a chest radiograph or computerized tomographic (CT) scan. These opacities are not fully explained by pleural effusions, lobar collapse, lung collapse, or pulmonary nodules. - Respiratory failure not fully explained by cardiac failure or fluid overload. - Moderate to severe impairment of oxygenation must be present, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2). The severity of the hypoxemia defines the severity of the ARDS: - Moderate ARDS: PaO2/FiO2 >100 mmHg and =200 mmHg, on ventilator settings that include PEEP =5 cm H2O OR - Severe ARDS: PaO2/FiO2 =100 mmHg on ventilator settings that include PEEP =5 cm H2O - High sensitivity C-Reactive Protein (hs-CRP) or CRP serum level >4.0 mg/dL - Acute Physiologic and Chronic Health Evaluation (APACHE IV) score >5 - Creatinine clearance of = 30 mL/minute OR a creatinine clearance of 20-29 mL/minute with urine output of =0.3 mLs/kg/hour over the last 8 hours or =500 mLs over the last 24 hours - The patient or his/her legally authorized representative (LAR) is able to provide informed consent Exclusion Criteria - Currently receiving extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV) - Females who are pregnant or lactating - Patients with established positive bacterial blood cultures prior to enrollment or suspicion of superimposed bacterial pneumonia - Patients with BMI >55 - Patients with untreated HIV infection - Patients with malignancy who are within 12 months of active treatment with any chemotherapy, radiation or immunotherapy. - Patients who have been intubated for more than 72 hours in total at the time of randomization - Creatinine clearance less than 20 mL/minute or receiving renal replacement therapy - LFTs (isolated ALT or AST) > 8x upper limit of normal or > 5x upper limit of normal in the setting of other liver function abnormalities (i.e., total bilirubin = 2x upper limit of normal) - Known hypersensitivity to DMSO or to porcine or bovine proteins - History of prior respiratory disease with requirement for supplemental oxygen - Any end-stage organ disease which in the opinion of the investigator may possibly affect the safety of remestemcel-L treatment - Receiving an investigational cellular therapy agent |
Country | Name | City | State |
---|---|---|---|
United States | University of Michigan | Ann Arbor | Michigan |
United States | Emory University | Atlanta | Georgia |
United States | University of Maryland | Baltimore | Maryland |
United States | Brigham and Women's Hospital | Boston | Massachusetts |
United States | University of Virginia | Charlottesville | Virginia |
United States | Cleveland Clinic Foundation | Cleveland | Ohio |
United States | Duke University Medical Center | Durham | North Carolina |
United States | Lutheran Hospital | Fort Wayne | Indiana |
United States | Dignity Health | Gilbert | Arizona |
United States | Houston Methodist Hospital | Houston | Texas |
United States | Dartmouth-Hitchcock | Lebanon | New Hampshire |
United States | University of Southern California | Los Angeles | California |
United States | Ochsner Clinic | New Orleans | Louisiana |
United States | Mount Sinai Health | New York | New York |
United States | New York University Langone Health | New York | New York |
United States | Northwell Health | New York | New York |
United States | University of Pennsylvania Health System | Philadelphia | Pennsylvania |
United States | Baylor, Smith & White | Plano | Texas |
United States | Maine Medical Center | Portland | Maine |
United States | WakeMed | Raleigh | North Carolina |
United States | Stanford University | Stanford | California |
Lead Sponsor | Collaborator |
---|---|
Icahn School of Medicine at Mount Sinai | Mesoblast, Inc., National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of all-cause mortality | Number of all-cause mortality within 30 days of randomization. | 30 days | |
Secondary | Number of days alive off mechanical ventilatory support | 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. | 60 days | |
Secondary | Number of adverse events | 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. | 30 days | |
Secondary | Number of participants alive at day 7 | 7 days | ||
Secondary | Number of participants alive at day 14 | 14 days | ||
Secondary | Number of participants alive at day 60 | 60 days | ||
Secondary | Number of participants alive at day 90 | 90 days | ||
Secondary | Number of participants alive at 12 Months | 12 Months | ||
Secondary | Number of participants with resolution and/or improvement of ARDS | The number and percent of patients with resolution and/or improvement of ARDS at day 7 | 7 days | |
Secondary | Number of participants with resolution and/or improvement of ARDS | The number and percent of patients with resolution and/or improvement of ARDS at day 14 | 14 days | |
Secondary | Number of participants with resolution and/or improvement of ARDS | The number and percent of patients with resolution and/or improvement of ARDS at day 21 | 21 days | |
Secondary | Number of participants with resolution and/or improvement of ARDS | The number and percent of patients with resolution and/or improvement of ARDS at day 30 | 30 days | |
Secondary | Severity of ARDS | 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. | baseline and 7 days | |
Secondary | Severity of ARDS | 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. | baseline and 14 days | |
Secondary | Severity of ARDS | 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. | baseline and 21 days | |
Secondary | Severity of ARDS | 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. | baseline and 30 days | |
Secondary | Length of stay | Hospital length of stay | 12 months | |
Secondary | Readmissions | number of readmission | 12 months | |
Secondary | Length of Stay in Intensive Care Unit | 12 months | ||
Secondary | Clinical Improvement Scale | 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. | 7 days | |
Secondary | Clinical Improvement Scale | Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement. | 14 days | |
Secondary | Clinical Improvement Scale | 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. | 21 days | |
Secondary | Clinical Improvement Scale | 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. | 30 days | |
Secondary | Change in plasma hs-CRP concentration | Changes from baseline in plasma hs-CRP concentration at days 7 | baseline and 7 days | |
Secondary | Change in plasma hs-CRP concentration | Changes from baseline in plasma hs-CRP concentration at days 14 | baseline and 14 days | |
Secondary | Change in plasma hs-CRP concentration | Changes from baseline in plasma hs-CRP concentration at days 21 | baseline and 21 days | |
Secondary | Change in serum hs-CRP concentration | Changes from baseline in serum hs-CRP concentration at days 30 | baseline and 30 days | |
Secondary | Change in IL-6 inflammatory marker level | Changes from baseline in IL-6 inflammatory marker level at 7 days | baseline and 7 days | |
Secondary | Change in IL-6 inflammatory marker level | Changes from baseline in IL-6 inflammatory marker level at 14 days | baseline and 14 days | |
Secondary | Change in IL-6 inflammatory marker level | Changes from baseline in IL-6 inflammatory marker level at 21 days | baseline and 21 days | |
Secondary | Change in IL-6 inflammatory marker level | Changes from baseline in IL-6 inflammatory marker level at 30 days | baseline and 30 days | |
Secondary | Change in IL-8 inflammatory marker level | Changes from baseline in IL-6 inflammatory marker level at 7 days | baseline and 7 days | |
Secondary | Change in IL-8 inflammatory marker level | Changes from baseline in IL-6 inflammatory marker level at 21 days | baseline and 21 days | |
Secondary | Change in IL-8 inflammatory marker level | Changes from baseline in IL-6 inflammatory marker level at 14 days | baseline and 14 days | |
Secondary | Change in IL-8 inflammatory marker level | Changes from baseline in IL-6 inflammatory marker level at 30 days | baseline and 30 days | |
Secondary | Change in TNF-alpha inflammatory marker level | Changes from baseline in TNF-alpha inflammatory marker level at 7 days | baseline and 7 days | |
Secondary | Change in TNF-alpha inflammatory marker level | Changes from baseline in TNF-alpha inflammatory marker level at 14 days | baseline and 14 days | |
Secondary | Change in TNF-alpha inflammatory marker level | Changes from baseline in TNF-alpha inflammatory marker level at 21 days | baseline and 21 days | |
Secondary | Change in TNF-alpha inflammatory marker level | Changes from baseline in TNF-alpha inflammatory marker level at 30 days | baseline and 30 days | |
Secondary | Pulmonary symptoms | including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization | 6 months | |
Secondary | Pulmonary symptoms | including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization | 12 months |
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