Acute Respiratory Distress Syndrome, Covid19
Conditions
Brief summary
This is a Phase 2 multicenter randomized (2:1), placebo-controlled trial to evaluate early signs of efficacy of allogeneic, umbilical cord-derived (UC) mesenchymal stromal cells (MSCs) in patients with COVID-19 and Acute Respiratory Distress Syndrome (ARDS). Randomized participants (N=54) will receive 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) or blinded placebo. The MSC product will be provided as 2.5 million cells/ml suspended in PlasmaLyte A containing 5% Human Albumin. The appearance-matched placebo product contains the same excipients, PlasmaLyte A and 5% Human Albumin, as the UC-MSCs.
Interventions
BIOLOGICALUC-MSCs
3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)
BIOLOGICALPlacebo
PlasmaLyte A and 5% Human Albumin
Sponsors
Canadian Institutes of Health Research (CIHR)
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized (2:1) placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age of ≥18 years * Laboratory-confirmed SARS-CoV-2 infection during the current admission * On invasive, non-invasive mechanical ventilation (NIV) (PEEP ≥5 cmH20) or high-flow nasal canula (HFNC) oxygen therapy (minimum total flow rate of 40 lpm) * ARDS (onset \<96h) as per the international consensus definition (P/F ratio \< 300 with PEEP ≥5cm H20 or on HFNC), not due primarily to cardiac causes.
Exclusion criteria
* No consent/inability to obtain consent * Rockwood Clinical Frailty Score \> 4 * Moribund patient not expected to survive 24 hours * Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50% * Currently receiving extracorporeal life support * Pregnant or lactating * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Moderate to severe chronic liver disease (Childs-Pugh Score \> 12) * Severe chronic respiratory disease with a baseline PaCO2 \> 50 mm Hg or the use of home oxygen * Documented deep venous thrombosis or pulmonary embolism within the preceding 3 months * Inability/contra-indications to receiving local standard of care thromboprophylaxis * Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use \>6months) * Known HIV, Hep B/C positive, or active tuberculosis * Multisystem shock (SOFA score change from baseline of \>2 in \>2 systems) * Patient, surrogate, or physician not committed to full support including intubation (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28 | Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers of systemic inflammatory response | Change from Baseline to 24 hours after each MSC infusion | Interleukin levels change from Baseline to 24 hours after each MSC infusion |
| Biomarkers of endothelial function | Change from Baseline to 24 hours after each MSC infusion | Angiopoietin levels change from Baseline to 24 hours after each MSC infusion |
| ICU mortality | Day 28 | Number of deaths at day 28 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety events (SAEs, AEs) | At time of infusion until one year post-infusion | allergic reactions, infusion related reactions, and venous and arterial thrombotic events |
Countries
Canada
Outcome results
None listed