Efficacy and Safety Evaluation of Mesenchymal Stem Cells for the Treatment of Patients With Respiratory Distress Due to COVID-19

Banc de Sang i Teixits26 enrolled

Overview

Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.

This is a prospective, double-blind, randomized, parallel, placebo-controlled pilot clinical trial to assess the efficacy and safety of two infusions of Wharton Jelly mesenchymal stromal cells (WJ-MSC) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. The study will enroll 30 patients who after signing the informed consent will be checked for inclusion and exclusion criteria. Patients will then be randomized (1:1) to one of the 2 treatment arms: Treatment A WJ-MSC/WJ-MSC; Treatment B Placebo/ Placebo. The 2 infusions will be administered endovenously on day 1 (D1) and on D3. Thereafter, patients will be followed-up on days 3, 5, 7, 14, 21, and 28 Once the study is completed, controls will be established at 3 months, 6 months and 12 months as long-term follow-up. The study treatments (A or B) will be added on top of the Standard of Care treatment prescribed by the attending physician. Each dose of MSC-WJ will consist of the intravenous administration of 1E6cells/Kg. Recruitment will be competitive for the centers participating in the study. A Data Safety and Monitoring Board (DSMB) will be established to review safety and efficacy along the trial.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Positive PCR fpr SARS-CoV-2 2. Intensive Care Unit admission for less than 3 days 3. Moderate acute respiratory distress (Berlin criteria definition with 100 mmHg \< PaO2/FiO2 ≤ 200 mmHg) 4. Male or female, aged 18 to 70 years old 5. Signed informed consent by the patient or by a legal representative (in this case, can be obtained by phone, although it must be confirmed in writing later, accepted by email) Exclusion Criteria: 1. Expected survival less than 3 days 2. Treatment with immunosuppressive drugs (tocilizumab, sarilumab) with corticosteroids being allowed 3. Neoplastic disease either active or without complete remission 4. Immunosuppressed patients (except treatment with corticosteroids for respiratory distress) 5. Pregnant or lactating women 6. Participation in another clinical trial with an experimental drug in the last 30 days 7. Other pathologies that, in medical judgment, contraindicate participation in the study

Locations (5)

Hospital de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Mútua de Terrassa

Terrassa, Barcelona, Spain

Hospital del Mar

Barcelona, Spain

Hospital Vall d'Hebron

Barcelona, Spain

Hospital Clínic de Barcelona

Barcelona, Spain

Outcomes

Primary Outcomes

All-cause mortality at day 28

Number of patients who died, by treatment group

Time frame: Day 28

Secondary Outcomes

Safety of WJ-MSC

Number of patients with treatment-emergent adverse events, by treatment group

Time frame: Day 28

Need for treatment with rescue medication

Number of patients who, after the start of treatment, required rescue medication, by treatment group

Time frame: Day 28

Need and duration of mechanical ventilation

Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group

Time frame: Day 28

Ventilator free days

Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.

Time frame: Day 28

Evolution of PaO2 / FiO2 ratio

Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.

Time frame: Day 28

Evolution of the SOFA index

Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group.

Time frame: Day 28

Evolution of the APACHE II score

Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group.

Time frame: Day 28

Duration of hospitalization

Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.

Time frame: Day 28

Evolution of markers of immune response (leucocyte count, neutrophils)

Variation in the count and percentage of leukocytes and neutrophils, by treatment group.

Time frame: Day 28

Feasibility of WJ-MSC administration

Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date

Time frame: Day 28

Feasibility of WJ-MSC administration

Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment.

Time frame: Day 28

Evolution of disease biomarker: polymerase chain reaction (RT-PCR)

Variation in the values of the biomarker, by treatment group.

Time frame: Day 28

Evolution of disease biomarker: lactate dehydrogenase (LDH)

Variation in the values of the biomarker, by treatment group.

Time frame: Day 28

Evolution of disease biomarker: D-dimer

Variation in the values of the biomarker, by treatment group.

Time frame: Day 28

Evolution of disease biomarker: Ferritin

Variation in the values of the biomarker, by treatment group.

Time frame: Day 28

Efficacy and Safety Evaluation of Mesenchymal Stem Cells for the Treatment of Patients With Respiratory Distress Due to COVID-19

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes