Clinical Trial to Assess the Efficacy of MSC in Patients With ARDS Due to COVID-19

Study Overview
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Brief Summary
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A double-blind, randomized, controlled, clinical trial to evaluate the efficacy and safety of MSC (mesenchymal stromal cells) intravenous administration in patients with COVID-induced ARDS compared to a control arm.

Detailed Description
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A double-blind, randomized, controlled, clinical trial to evaluate the efficacy and safety of MSC (mesenchymal stromal cells) intravenous administration in patients with COVID-induced ARDS compared to a control arm. All trial participants will receive SOC*. Randomization will be 1:1 between: Treatment arm: allogenic MSC. Control arm: Placebo (solution with the same composition as the experimental treatment, without the MSC). SOC can include any medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.).

Official Title
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Double-blind, Randomized, Controlled, Clinical Trial to Assess the Efficacy of Allogenic Mesenchymal Stromal Cells in Patients With Acute Respiratory Distress Syndrome Due to COVID-19

Conditions
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Acute Respiratory Distress Syndrome, COVID-19 Pneumonia

Intervention / Treatment
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* Biological: Mesenchymal stromal cells
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. Adult patients ≥18 years of age at the time of enrolment. Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigenic tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. Patients requiring invasive ventilation are eligible within 72 hours from intubation. Eligible for ICU admission, according to the clinical team. Exclusion Criteria: Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). Do Not Attempt Resuscitation order in place. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment. History of a moderate/severe lung disorder requiring home-based oxygen therapy. Patient requiring ECMO, hemodialysis or hemofiltration at the time of treatment administration. Current diagnosis of pulmonary embolism. Active neoplasm, except carcinoma in situ or basalioma. Known allergy to the products involved in the allogenic MSC production process. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrollment). Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal Stromal cells<br>Approximately 1x10E6 MSC/kg | Biological: Mesenchymal stromal cells<br>* Administration of one single dose of allogenic Mesenchymal stromal cells<br>|
| Placebo Comparator: Control group<br>Solution identical to experimental treatment, without the MSC | Other: Placebo<br>* Administration of placebo (solution identical to experimental treatment, without the MSC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the PaO2/FiO2* ratio from baseline to day 7 of treatment administration | Primary endpoint | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Secondary endpoint | Days 7, 14, and 28 after treatment | 
| Time to PaO2/FiO2 ratio greater than 200 mmHg | Secondary endpoint | 12 months | 
| Clinical status on the World Health Organization ordinal scale | Secondary endpoint. Categories: Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities. Hospitalized, not requiring supplemental oxygen. Hospitalized, requiring supplemental oxygen. Hospitalized, on non-invasive ventilation or high flow oxygen devices. Hospitalized, on invasive mechanical ventilation or ECMO . Death. | Baseline, daily until day 14, and on day 28 after treatment | 
| PaO2/FiO2 ratio | Secondary endpoint | Baseline and days 2, 4, 14 and 28 after treatment | 
| SOFA score | Secondary endpoint Sequential Organ Failure Assessment score (0-24) | Baseline and days 2, 4, 7, 14 and 28 after treatment | 
| Oxygen therapy-free days | Secondary endpoint | Day 28 | 
| Duration of hospitalization | Secondary endpoint | 12 months | 
| Duration of ICU admission | Secondary endpoint | 12 months | 
| Incidence of non-invasive ventilation | Secondary endpoint Proportion of patients with non-invasive ventilation | Day 28 | 
| Incidence of invasive mechanical ventilation | Secondary endpoint Proportion of patients with invasive mechanical ventilation | Day 28 | 
| Duration of non-invasive ventilation | Secondary endpoint (number of days) | Day 28 | 
| Duration of invasive mechanical ventilation | Secondary endpoint (number of days) | Day 28 | 
| Mechanical ventilation-free days | Secondary endpoint | Day 28 | 
| Survival rate | Secondary endpoint | 3 and 12 months. | 
| Cumulative incidence SAEs, Grade 3 and 4 AEs, ADR and AEs of special interest. | Secondary endpoint | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, COVID-19 Pneumonia, Mesenchymal stromal cells, Coronavirus, SARS-CoV-2