Adult Respiratory Distress Syndrome, COVID-19, SARS-CoV 2
Conditions
Keywords
ARDS
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.
Interventions
DRUGXCEL-UMC-BETA
Administration on top of the standard administered treatment
OTHERPlacebo
Administration on top of the standard administered treatment
Sponsors
Banc de Sang i Teixits
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality at day 28 | Day 28 | Number of patients who died, by treatment group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evolution of PaO2 / FiO2 ratio | Day 28 | Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group. |
| Evolution of markers of immune response (leucocyte count, neutrophils) | Day 28 | Variation in the count and percentage of leukocytes and neutrophils, by treatment group. |
| Feasibility of WJ-MSC administration | Day 28 | Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date |
| Evolution of disease biomarker: polymerase chain reaction (RT-PCR) | Day 28 | Variation in the values of the biomarker, by treatment group. |
| Evolution of disease biomarker: lactate dehydrogenase (LDH) | Day 28 | Variation in the values of the biomarker, by treatment group. |
| Evolution of disease biomarker: D-dimer | Day 28 | Variation in the values of the biomarker, by treatment group. |
| Evolution of disease biomarker: Ferritin | Day 28 | Variation in the values of the biomarker, by treatment group. |
| Safety of WJ-MSC | Day 28 | Number of patients with treatment-emergent adverse events, by treatment group |
| Need for treatment with rescue medication | Day 28 | Number of patients who, after the start of treatment, required rescue medication, by treatment group |
| Need and duration of mechanical ventilation | Day 28 | Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group |
| Ventilator free days | Day 28 | Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group. |
| Evolution of the SOFA index | Day 28 | Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group. |
| Evolution of the APACHE II score | Day 28 | Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group. |
| Duration of hospitalization | Day 28 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Study of reactivity against SARS-CoV-2 peptides | Day 28 | Reactivity will be assessed using ELISPOT |
| Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides | Day 28 | Blood sample analysis |
| Genetic variability of patient's genotype in response to treatment | Day 28 | Blood sample analysis for the patient's genomic sequencing |
| Genetic variability of the SARS-CoV-2 genotype in response to treatment | Day 28 | Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample |
| Analysis of subpopulations of lymphocytes and immunoglobulins | Day 28 | Blood sample analysis |
| Evaluation of the in vitro response of the receptor lymphocytes | Day 28 | In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech) |
Countries
Spain
Outcome results
None listed