Clinical trial NCT04865107: Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial
Official title: Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Covid19
Acute Respiratory Distress Syndrome
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2021-04-29
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized (2:1) placebo-controlled trial
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28
timeFrame: Day 28
Secondary outcomes:
measure: Biomarkers of systemic inflammatory response
timeFrame: Change from Baseline to 24 hours after each MSC infusion
measure: Biomarkers of endothelial function
timeFrame: Change from Baseline to 24 hours after each MSC infusion
measure: ICU mortality
timeFrame: Day 28
Other outcomes:
measure: Safety events (SAEs, AEs)
timeFrame: At time of infusion until one year post-infusion
Locations:
city: Oshawa
country: Canada
facility: Lakeridge Health
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: The Ottawa Hospital
name: Duncan J Stewart, MD
role: PRINCIPAL_INVESTIGATOR
References: