MSC-based Therapy in COVID-19-associated Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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Considering the potential of mesenchymal stromal cells (MSCs) in the treatment of lung injuries by COVID-19, this pilot clinical trial evaluates the safety and potential efficacy of the cell therapy, administered intravenously, in patients with pneumonia associated with COVID-19-associated acute respiratory distress syndrome.

Official Title
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Mesenchymal Stromal Cell-based Therapy for COVID-19-associated Acute Respiratory Distress Syndrome: a Pilot Clinical Study

Conditions
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Covid19, ARDS, Human

Intervention / Treatment
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* Other: Mesenchymal stromal cell-based therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of COVID-19 confirmed by RT-PCR; Thorax CT image suggestive of viral pneumonia; Respiratory failure (SaO2 <93% with O2 at 5L / min) Tracheal intubation (first 48 h); Exclusion Criteria: Pregnancy or breastfeeding; Patients with a history of cancer, chemotherapy in the past 2 years; Life expectancy less than 6 months or in exclusive palliative care; Severe liver failure, with Child-Pugh score> 12; High probability of death in the following 48 h; Previous renal failure: patients who were already on dialysis or patients with RFG <30ml / min / 1.73 m2; Clinical or radiological suspicion of tuberculosis and bacterial pneumonia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Patients will receive standard care. | |
| Experimental: MSC - low dose (2.5x10ˆ7)<br>Patients will receive standard care plus cell therapy. | Other: Mesenchymal stromal cell-based therapy<br>* Intravenous administration of MSCs, performed as single dose (high dose group) or repeated after 48 h (low doses; intermediate dose)<br>|
| Experimental: MSC - intermediate dose (5x10ˆ7)<br>Patients will receive standard care plus cell therapy. | Other: Mesenchymal stromal cell-based therapy<br>* Intravenous administration of MSCs, performed as single dose (high dose group) or repeated after 48 h (low doses; intermediate dose)<br>|
| Experimental: MSC - high dose (10x10ˆ7)<br>Patients will receive standard care plus cell therapy. | Other: Mesenchymal stromal cell-based therapy<br>* Intravenous administration of MSCs, performed as single dose (high dose group) or repeated after 48 h (low doses; intermediate dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intrahospital mortality |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay in the ICU and Hospital |  | 28 days | 
| Days without mechanical ventilation in 28 days |  | 28 days | 
| PaO2 / FiO2 ratio |  | Day 1, Day 2 and Day 7 after cell infusion | 
| Incidence of secondary infections |  | 28 days | 
| Incidence of adverse events |  | 28 days | 
| Quantification of inflammatory response markers | Exploratory evaluation of changes from baseline (percentage) in serum levels of CRP, LDH, Ferritin levels, a panel of cytokines, chemokines immune cell populations by flow cytometry | Day 1, Day 3 and Day 7 after cell infusion |