MSCs in COVID-19 ARDS
- Conditions
- Remestemcel-LAcute Respiratory Distress SyndromeCOVIDMesenchymal Stromal Cells
- Interventions
- Biological: Remestemcel-LDrug: Placebo
- Registration Number
- NCT04371393
- Lead Sponsor
- Icahn School of Medicine at Mount Sinai
- Brief Summary
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.
- Detailed Description
This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial. Randomization will be stratified by clinical center and by moderate versus severe ARDS. The study is designed to have three interim analyses for stopping accrual early for efficacy and futility when 30%, 45% and 60% of the 300 patients have reached the primary endpoint using Bayesian predictive probabilities.
Patients will be randomized in a 1:1 allocation to intravenous infusion of MSCs (remestemcel-L) plus standard of care versus placebo plus standard of care for the treatment of COVID-19 related ARDS:
* Group 1: 2x10\^6 MSC/kg of body weight plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day)
* Group 2: Placebo (Plasma-Lyte) plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day) (control)
MSCs and placebo will initially be administered intravenously in the dose defined above at randomization. The rate of infusion may be tailored to the patient's respiratory status and fluid status, but the duration of infusion should not exceed 60 minutes.
Patients will be followed for 90 days post randomization, with assessment of pulmonary symptoms at 6 and 12 months.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 223
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Remestemcel-L Plus Standard of Care Remestemcel-L Intravenous infusion of remestemcel-L 2x10\^6 MSC/kg of body weight plus standard of care Placebo Plus Standard of Care Placebo Placebo (Plasma-Lyte) plus standard of care
- Primary Outcome Measures
Name Time Method Number of all-cause mortality 30 days Number of all-cause mortality within 30 days of randomization.
- Secondary Outcome Measures
Name Time Method Number of days alive off mechanical ventilatory support 60 days 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.
Number of participants alive at day 60 60 days Number of participants alive at day 90 90 days Number of participants alive at 12 Months 12 Months Number of participants with resolution and/or improvement of ARDS 30 days The number and percent of patients with resolution and/or improvement of ARDS at day 30
Severity of ARDS baseline and 30 days 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.
Length of stay 12 months Hospital length of stay
Readmissions 12 months number of readmission
Length of Stay in Intensive Care Unit 12 months Change in plasma hs-CRP concentration baseline and 21 days Changes from baseline in plasma hs-CRP concentration at days 21
Number of participants alive at day 7 7 days Number of participants alive at day 14 14 days Number of adverse events 30 days 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.
Clinical Improvement Scale 30 days 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.
Change in serum hs-CRP concentration baseline and 30 days Changes from baseline in serum hs-CRP concentration at days 30
Change in IL-6 inflammatory marker level baseline and 30 days Changes from baseline in IL-6 inflammatory marker level at 30 days
Change in IL-8 inflammatory marker level baseline and 30 days Changes from baseline in IL-6 inflammatory marker level at 30 days
Change in TNF-alpha inflammatory marker level baseline and 30 days Changes from baseline in TNF-alpha inflammatory marker level at 30 days
Pulmonary symptoms 12 months including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization
Trial Locations
- Locations (21)
Maine Medical Center
🇺🇸Portland, Maine, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Ochsner Clinic
🇺🇸New Orleans, Louisiana, United States
Dignity Health
🇺🇸Gilbert, Arizona, United States
Dartmouth-Hitchcock
🇺🇸Lebanon, New Hampshire, United States
WakeMed
🇺🇸Raleigh, North Carolina, United States
Stanford University
🇺🇸Stanford, California, United States
Lutheran Hospital
🇺🇸Fort Wayne, Indiana, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Mount Sinai Health
🇺🇸New York, New York, United States
New York University Langone Health
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Northwell Health
🇺🇸New York, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Pennsylvania Health System
🇺🇸Philadelphia, Pennsylvania, United States
Baylor, Smith & White
🇺🇸Plano, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States