Clinical trial NCT04615429: Clinical Trial to Assess the Efficacy of MSC in Patients With ARDS Due to COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Respiratory Distress Syndrome
COVID-19 Pneumonia
Keywords: Acute Respiratory Distress Syndrome
COVID-19 Pneumonia
Mesenchymal stromal cells
Coronavirus
SARS-CoV-2
Lead sponsor: Puerta de Hierro University Hospital
Sponsor class: OTHER
First posted: 2020-11-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in the PaO2/FiO2* ratio from baseline to day 7 of treatment administration
timeFrame: 7 days
Secondary outcomes:
measure: All-cause mortality
timeFrame: Days 7, 14, and 28 after treatment
measure: Time to PaO2/FiO2 ratio greater than 200 mmHg
timeFrame: 12 months
measure: Clinical status on the World Health Organization ordinal scale
timeFrame: Baseline, daily until day 14, and on day 28 after treatment
measure: PaO2/FiO2 ratio
timeFrame: Baseline and days 2, 4, 14 and 28 after treatment
measure: SOFA score
timeFrame: Baseline and days 2, 4, 7, 14 and 28 after treatment
measure: Oxygen therapy-free days
timeFrame: Day 28
measure: Duration of hospitalization
timeFrame: 12 months
measure: Duration of ICU admission
timeFrame: 12 months
measure: Incidence of non-invasive ventilation
timeFrame: Day 28
measure: Incidence of invasive mechanical ventilation
timeFrame: Day 28
measure: Duration of non-invasive ventilation
timeFrame: Day 28
measure: Duration of invasive mechanical ventilation
timeFrame: Day 28
measure: Mechanical ventilation-free days
timeFrame: Day 28
measure: Survival rate
timeFrame: 3 and 12 months.
measure: Cumulative incidence SAEs, Grade 3 and 4 AEs, ADR and AEs of special interest.
timeFrame: 12 months
Other outcomes:
measure: Analytical endpoints
timeFrame: Baseline and days 2, 4, 7, 14 and 28 after treatment
Locations:
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
state: Madrid
Study officials:
affiliation: Hematology Department. Hospital Universitario Puerta de Hierro
name: Rafael F Duarte, MD, PhD
role: STUDY_CHAIR
affiliation: Clinical Pharmacology Department. Hospital Universitario Puerta de Hierro
name: Cristina Avedano-Sola, MD, PhD
role: STUDY_CHAIR
affiliation: ICU. Hospital Universitario Puerta de Hierro
name: Juan J Rubio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Respiratory Medicine Department
name: Rosa Malo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Payares-Herrera C, Martinez-Munoz ME, Vallhonrat IL, de Molina RM, Torres MP, Trisan A, de Diego IS, Alonso R, Zafra R, Donaire T, Sanchez R, Rubio JJ, Duarte Palomino RF, Sola CA. Double-blind, randomized, controlled, trial to assess the efficacy of allogenic mesenchymal stromal cells in patients with acute respiratory distress syndrome due to COVID-19 (COVID-AT): A structured summary of a study protocol for a randomised controlled trial. Trials. 2021 Jan 6;22(1):9. doi: 10.1186/s13063-020-04964-1.