Mesenchymal Stem Cells (MSCs) in Inflammation-Resolution Programs of Coronavirus Disease 2019 (COVID-19) Induced Acute Respiratory Distress Syndrome (ARDS)

Study Overview
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Brief Summary
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To evaluate the safety, toxicity and immunological effects of infusion of allogeneic bone marrow-derived human mesenchymal stem (stromal) cells (MSCs) and whether this therapy has an influence on the resolution processes in ARDS patients infected with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Official Title
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Prospective Phase II Study: MSCs in Inflammation-Resolution Programs of SARS-CoV-2 Induced ARDS

Conditions
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ARDS, COVID-19

Intervention / Treatment
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* Biological: MSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COVID-19-positive subject Horowitz index ≤ 200 Bilateral opacities on frontal chest radiograph, and requirement for positive pressure ventilation via an endotracheal tube or non-invasive ventilation no clinical signs of left atrial hypertension detected via echocardiography, or if measured, a Pulmonary Arterial Wedge Pressure (PAOP) less than or equal to 18 mmHg. Subject's Age ≥ 18 years Exclusion Criteria: COVID-19-negative subject Subject's Age < 18 years More than 7 days since initiation of mechanical ventilation Patient, surrogate or physician not committed to full intensive care support. Positive Pregnancy test at the time of screening. Patients dependent on the sponsor, investigator and their employees, as well as persons dependent on the manufacturer of the investigational drug

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 |
| --- | --- |
| Experimental: MSC Treatment<br> | Biological: MSC<br>* infusion of allogeneic bone marrow-derived human mesenchymal stem (stromal) cells<br>|
| No Intervention: control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lung injury score | improvement of lung injury score (LIS), 0-16 points, severity increasing with higher points | day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| D-dimers | D-dimers blood levels | day 0, 1, 2, 3, 10 and 15 | 
| phenotype | distribution of phenotypes of immune cells | day 0, 1, 2, 3, 10 and 15 | 
| pro-resolving lipid mediators | Levels of specialized pro-resolving lipid mediators within alveolar macrophages and bronchoalveolar lavage | day 0, 1, 2, 3, 10 and 15 | 
| cytokines | Cytokine concentration within bronchoalveolar lavage and Serum prior and after MSC infusions | day 0, 1, 2, 3, 10 and 15 | 
| chemokines | Chemokine concentration within bronchoalveolar lavage and Serum prior and after MSC infusions | day 0, 1, 2, 3, 10 and 15 | 
| Survival | Survival at 10 days and 28 days | day 10 and 28 | 
| extubation | Time to removal of endotracheal tube | day 28 | 
| lymphocyte subpopulations | lymphocyte subpopulations in peripheral blood by flow cytometry prior and after MSC infusion (day 0,3,5,10) | day 0, 3, 5 and 10 | 
| SARS-CoV-2-specific antibody titers | evaluate SARS-CoV-2-specific antibody titers in the serum of patients prior and post MSC infusion. | day 0, 5 and 10 | 
| complement molecules (C5-C9) | evaluate levels of complement molecules (C5-C9) in the serum of patients prior and post MSC infusion | day 0, 5 and 10 |