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

Phase 2

• Conditions: Acute Respiratory Distress Syndrome; COVID-19 Pneumonia
• Interventions: Biological: Mesenchymal stromal cells; Other: Placebo

• Registration Number: NCT04615429
• Lead Sponsor: Cristina Avendaño Solá

Brief Summary

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

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.).

Study Timeline

• Study Start: 2020-09-15
• Study First Submitted: 2020-10-25
• Study First Submitted QC: 2020-11-02
• Study First Posted: 2020-11-04
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-09
• Last Update Posted: 2021-11-10
• Primary Completion: 2022-01
• Study Completion: 2022-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. 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.
2. Adult patients ≥18 years of age at the time of enrolment.
3. 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.
4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization.
5. Patients requiring invasive ventilation are eligible within 72 hours from intubation.
6. Eligible for ICU admission, according to the clinical team.

Exclusion Criteria

1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team).
2. "Do Not Attempt Resuscitation" order in place.
3. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment.
4. History of a moderate/severe lung disorder requiring home-based oxygen therapy.
5. Patient requiring ECMO, hemodialysis or hemofiltration at the time of treatment administration.
6. Current diagnosis of pulmonary embolism.
7. Active neoplasm, except carcinoma in situ or basalioma.
8. Known allergy to the products involved in the allogenic MSC production process.
9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrollment).
10. 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).
11. Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mesenchymal Stromal cells	Mesenchymal stromal cells	Approximately 1x10E6 MSC/kg
Control group	Placebo	Solution identical to experimental treatment, without the MSC

Primary Outcome Measures

Name	Time	Method
Change in the PaO2/FiO2* ratio from baseline to day 7 of treatment administration	7 days	Primary endpoint

Secondary Outcome Measures

Name	Time	Method
All-cause mortality	Days 7, 14, and 28 after treatment	Secondary endpoint
Clinical status on the World Health Organization ordinal scale	Baseline, daily until day 14, and on day 28 after treatment	Secondary endpoint.; Categories: 1. Not hospitalized, no limitations on activities.; 2. Not hospitalized, limitation on activities.; 3. Hospitalized, not requiring supplemental oxygen.; 4. Hospitalized, requiring supplemental oxygen.; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices.; 6. Hospitalized, on invasive mechanical ventilation or ECMO .; 7. Death.
SOFA score	Baseline and days 2, 4, 7, 14 and 28 after treatment	Secondary endpoint Sequential Organ Failure Assessment score (0-24)
Incidence of invasive mechanical ventilation	Day 28	Secondary endpoint Proportion of patients with invasive mechanical ventilation
Oxygen therapy-free days	Day 28	Secondary endpoint
Mechanical ventilation-free days	Day 28	Secondary endpoint
PaO2/FiO2 ratio	Baseline and days 2, 4, 14 and 28 after treatment	Secondary endpoint
Incidence of non-invasive ventilation	Day 28	Secondary endpoint Proportion of patients with non-invasive ventilation
Duration of invasive mechanical ventilation	Day 28	Secondary endpoint (number of days)
Cumulative incidence SAEs, Grade 3 and 4 AEs, ADR and AEs of special interest.	12 months	Secondary endpoint
Time to PaO2/FiO2 ratio greater than 200 mmHg	12 months	Secondary endpoint
Duration of hospitalization	12 months	Secondary endpoint
Duration of ICU admission	12 months	Secondary endpoint
Duration of non-invasive ventilation	Day 28	Secondary endpoint (number of days)
Survival rate	3 and 12 months.	Secondary endpoint

Trial Locations

Locations (1)

Hospital Universitario Puerta de Hierro-Majadahonda; 🇪🇸 Majadahonda, Madrid, Spain