Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial

NCT04865107 | Completed Phase 2 DMC

• 1 other identifier: CIRCA-19 RCT
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

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.

Conditions

Covid19; Acute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28

  Day 28

Secondary Outcomes (3)

• Biomarkers of systemic inflammatory response

  Change from Baseline to 24 hours after each MSC infusion

• Biomarkers of endothelial function

  Change from Baseline to 24 hours after each MSC infusion

• ICU mortality

  Day 28

Other Outcomes (1)

• Safety events (SAEs, AEs)

  At time of infusion until one year post-infusion

Study Arms (2)

MSCs Arm

EXPERIMENTAL

3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)

Biological: UC-MSCs

Placebo Arm

PLACEBO COMPARATOR

3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)

Biological: Placebo

Interventions

UC-MSCs BIOLOGICAL

3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)

MSCs Arm

Placebo BIOLOGICAL

PlasmaLyte A and 5% Human Albumin

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (4)

Lakeridge Health

Oshawa, Ontario, ON L1G 2B9, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 3E4, Canada

Location

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Duncan J Stewart, MD

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized (2:1) placebo-controlled trial

Study Record Dates

• First Submitted: April 27, 2021
• First Posted: April 29, 2021
• Study Start: April 27, 2021
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)