Covid19Phase 2CIRCA-19 RCTNCT04865107
Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial
A Phase 2 study testing UC-MSCs in people with Covid19 and Acute Respiratory Distress Syndrome, run by Ottawa Hospital Research Institute at 4 sites in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Acute Respiratory Distress Syndrome
- What is being tested?
- UC-MSCs
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 4 sitesCanada
- Study dates
- 27 Apr 2021to 1 Apr 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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)
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, H2X 3E4
Lakeridge Health
Oshawa, Ontario, ON L1G 2B9
The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
About this study
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
- Being tested
- UC-MSCs, Placebo
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UC-MSCsBiological
3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)
PlaceboBiological
PlasmaLyte A and 5% Human Albumin
| Study group | Role | What they receive |
|---|---|---|
| MSCs Arm | Experimental | 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) Receives: 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) Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28
Measured: Day 28
Secondary outcomes (3)
Biomarkers of systemic inflammatory response
Interleukin levels change from Baseline to 24 hours after each MSC infusion
Measured: Change from Baseline to 24 hours after each MSC infusion
Biomarkers of endothelial function
Angiopoietin levels change from Baseline to 24 hours after each MSC infusion
Measured: Change from Baseline to 24 hours after each MSC infusion
ICU mortality
Number of deaths at day 28
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2021
- Study start27 Apr 2021
- Primary completion1 Apr 2022
- Study completion1 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized (2:1) placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Duncan J Stewart, MD, Principal investigator, The Ottawa Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04865107
- Sponsor's protocol ID
- CIRCA-19 RCT
- Acronym
- CIRCA-19 RCT
- Status last verified
- Jul 2025
- First submitted
- 27 Apr 2021
- Last updated
- 31 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04865107
- Acronym / sponsor ID
- CIRCA-19 RCT / CIRCA-19 RCT
- Conditions
- Covid19, Acute Respiratory Distress Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 27 Apr 2021 (actual)
- Primary completion
- 1 Apr 2022 (actual)
- Study completion
- 1 Apr 2022 (actual)
- First posted
- 29 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized (2:1) placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| MSCs Arm | Experimental | Biological: UC-MSCs3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) |
| Placebo Arm | Placebo comparator | Biological: Placebo3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UC-MSCs3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) | Biological | MSCs Arm |
| PlaceboPlasmaLyte A and 5% Human Albumin | Biological | Placebo Arm |
Primary outcome
Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28
Time frame: Day 28
3 secondary outcomes
Biomarkers of systemic inflammatory response
Time frame: Change from Baseline to 24 hours after each MSC infusion
Biomarkers of endothelial function
Time frame: Change from Baseline to 24 hours after each MSC infusion
ICU mortality
Time frame: Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Duncan J Stewart, MD principal investigator
The Ottawa Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing UC-MSCs in people with Covid19 and Acute Respiratory Distress Syndrome, run by Ottawa Hospital Research Institute at 4 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28 (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2025.