Acute Respiratory Distress Syndrome, COVID-19 Pneumonia
Conditions
Keywords
Acute Respiratory Distress Syndrome, COVID-19 Pneumonia, Mesenchymal stromal cells, Coronavirus, SARS-CoV-2
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.).
Interventions
BIOLOGICALMesenchymal stromal cells
Administration of one single dose of allogenic Mesenchymal stromal cells
OTHERPlacebo
Administration of placebo (solution identical to experimental treatment, without the MSC)
Sponsors
Cristina Avendaño Solá
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the PaO2/FiO2* Ratio From Baseline to Day 7 of Treatment Administration | 7 days | Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. If an arterial blood gas result cannot be obtained, the SaO2/FiO2 ratio could be substituted for the PaO2/FiO2 ratio |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of ≥1 Category at World Health Organization 7 Point Scale | From baseline until day 7, 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. |
| Time to Improvement of ≥1 Category at WHO 7-point Scale | 28 days | — |
| Patients That Had Oxygen Therapy Withdrawn by Day 28 | 28 days | — |
| Time to Discontinuation of Oxygen Therapy (WHO ≤3) | 28 days | — |
| Proportion of Patients That Were Discharged at Day 28 | 28 days | — |
| Duration of Hospitalization | 28 days | — |
| Proportion of Patients That Required ICU Admission | 12 months | — |
| Duration of ICU Admission | 12 months | — |
| Mortality at Day 28 | 28 days | — |
| Mortality at 12 Months | 12 months | — |
| New Onset Fibrosis at 12 Months | 12 months | New onset fibrosis at 12 months based on CT/X-ray imagine and pulmonary function tests. |
Countries
Spain
Contacts
STUDY_CHAIRRafael F Duarte, MD, PhD
Hematology Department. Hospital Universitario Puerta de Hierro
STUDY_CHAIRCristina Avedano-Sola, MD, PhD
Clinical Pharmacology Department. Hospital Universitario Puerta de Hierro
PRINCIPAL_INVESTIGATORJuan J Rubio, MD, PhD
ICU. Hospital Universitario Puerta de Hierro
PRINCIPAL_INVESTIGATORRosa Malo, MD
Respiratory Medicine Department
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 59.5 years |
| Body Mass Index | 29.0 Kg/m2 STANDARD_DEVIATION 3.1 |
| Comorbidities Cardiovascular disorder (including HBP) | 6 participants |
| Comorbidities Chronic lung disease | 3 participants |
| Comorbidities Diabetes mellitus | 2 participants |
| Comorbidities Obesity | 6 participants |
| Concomitant treatments Glucocorticoid therapy | 10 participants |
| Concomitant treatments Low molecular weight heparin | 10 participants |
| Concomitant treatments Remdesivir | 0 participants |
| Concomitant treatments Tocilizumab | 19 participants |
| C-reactive protein | 95.64 mg/L STANDARD_DEVIATION 111.54 |
| D-dimer | 1360.00 ng/mL STANDARD_DEVIATION 279.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 167.8 cm STANDARD_DEVIATION 10.1 |
| IL-6 | 307.95 pg/mL STANDARD_DEVIATION 380.18 |
| LDH | 379.95 U/L STANDARD_DEVIATION 123.51 |
| Lymphocytes | 0.88 cells*10^3/microL STANDARD_DEVIATION 0.59 |
| Neutrophil-lymphocyte ratio | 14.95 Neutrophil-lymphocyte ratio STANDARD_DEVIATION 6.79 |
| PaO2/FiO2 ratio at baseline | 95.3 ratio of PAO2/FiO2 STANDARD_DEVIATION 39.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment Spain | 10 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 13 Participants |
| Time from symptom onset to randomization | 11.5 days |
| Weight | 82.5 Kg STANDARD_DEVIATION 16 |
| WHO Score (7 points) 4: Hospitalized, requiring supplemental oxygen by mask or nasal prongs | 1 participants |
| WHO Score (7 points) 5: Hospitalized, on non-invasive ventilation or high flow devices | 6 participants |
| WHO Score (7 points) 6: Hospitalized, on invasive mechanical ventilation | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 1 / 10 |
| other Total, other adverse events | 1 / 10 | 0 / 10 |
| serious Total, serious adverse events | 3 / 10 | 7 / 10 |
Outcome results
None listed