Clinical trial NCT04390139: Efficacy and Safety Evaluation of Mesenchymal Stem Cells for the Treatment of Patients With Respiratory Distress Due to COVID-19
Official title: A Prospective, Double-blind, Randomized, Parallel, Placebo-controlled Pilot Clinical Trial for the Evaluation of the Efficacy and Safety of Two Doses of WJ-MSC in Patients With Acute Respiratory Distress Syndrome Secondary to Infection by COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
SARS-CoV 2
Adult Respiratory Distress Syndrome
Keywords: ARDS
Lead sponsor: Banc de Sang i Teixits
Sponsor class: OTHER
First posted: 2020-05-15
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause mortality at day 28
timeFrame: Day 28
Secondary outcomes:
measure: Safety of WJ-MSC
timeFrame: Day 28
measure: Need for treatment with rescue medication
timeFrame: Day 28
measure: Need and duration of mechanical ventilation
timeFrame: Day 28
measure: Ventilator free days
timeFrame: Day 28
measure: Evolution of PaO2 / FiO2 ratio
timeFrame: Day 28
measure: Evolution of the SOFA index
timeFrame: Day 28
measure: Evolution of the APACHE II score
timeFrame: Day 28
measure: Duration of hospitalization
timeFrame: Day 28
measure: Evolution of markers of immune response (leucocyte count, neutrophils)
timeFrame: Day 28
measure: Feasibility of WJ-MSC administration
timeFrame: Day 28
measure: Feasibility of WJ-MSC administration
timeFrame: Day 28
measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR)
timeFrame: Day 28
measure: Evolution of disease biomarker: lactate dehydrogenase (LDH)
timeFrame: Day 28
measure: Evolution of disease biomarker: D-dimer
timeFrame: Day 28
measure: Evolution of disease biomarker: Ferritin
timeFrame: Day 28
Other outcomes:
measure: Analysis of subpopulations of lymphocytes and immunoglobulins
timeFrame: Day 28
measure: Evaluation of the in vitro response of the receptor lymphocytes
timeFrame: Day 28
measure: Study of reactivity against SARS-CoV-2 peptides
timeFrame: Day 28
measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides
timeFrame: Day 28
measure: Genetic variability of patient's genotype in response to treatment
timeFrame: Day 28
measure: Genetic variability of the SARS-CoV-2 genotype in response to treatment
timeFrame: Day 28
Locations:
city: Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
state: Barcelona
city: Terrassa
country: Spain
facility: Mútua de Terrassa
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Antoni Torres, MD, PhD
role: STUDY_CHAIR
References: