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

Covid19 Clinical Trial

— CIRCA-19 RCT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04865107
• Other study ID #: CIRCA-19 RCT
• Status: Recruiting
• Phase: Phase 2
• Start date: April 27, 2021
• Est. completion date: April 2022

Study information

• Verified date: May 2021
• Source: Ottawa Hospital Research Institute
• Contact: Duncan J Stewart, MD
• Phone: 613-798-5555
• Email: djstewart[@]ohri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: April 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Covid19
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Biological:
• UC-MSCs
3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)
• Placebo
PlasmaLyte A and 5% Human Albumin

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec
Canada	Lakeridge Health	Oshawa	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety events (SAEs, AEs)	allergic reactions, infusion related reactions, and venous and arterial thrombotic events	At time of infusion until one year post-infusion
Primary	Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28		Day 28
Secondary	Biomarkers of systemic inflammatory response	Interleukin levels change from Baseline to 24 hours after each MSC infusion	Change from Baseline to 24 hours after each MSC infusion
Secondary	Biomarkers of endothelial function	Angiopoietin levels change from Baseline to 24 hours after each MSC infusion	Change from Baseline to 24 hours after each MSC infusion
Secondary	ICU mortality	Number of deaths at day 28	Day 28