Acute Respiratory Distress Syndrome (ARDS), Pneumonia, Severe Acute Respiratory Syndrome (SARS)
Conditions
Keywords
SARS-CoV-2, intravenous therapy, extracellular vesicles, ARDS, mesenchymal cells
Brief summary
This is a phase I/II, randomized, double-blind, placebo-controlled clinical trial that will evaluate the safety and potential efficacy of therapy with extracellular vesicles (EVs) obtained from mesenchymal stromal cells (MSCs), patients with moderate to severe acute respiratory distress syndrome due to COVID-19 or other etiology. Participants will be allocated to receive EVs obtained from MSCs or placebo (equal volume of Plasma-Lyte A). Blinding will cover the participants, the multidisciplinary intensive care team and the investigators.
Detailed description
The studied population will consist of 15 patients diagnosed with acute respiratory failure syndrome admitted to the intensive care unit of Hospital São Rafael. This research aims to assess the safety and potential effectiveness of intravenous therapy using extracellular vesicles derived from mesenchymal cells in patients with moderate to severe acute respiratory distress syndrome. The treatment group will receive intravenous administration of extracellular vesicles obtained from mesenchymal cells, while the control group will receive a placebo. EV group: will consist of 10 participants who will receive two infusions of 25 mL of the investigational product (Plasma-Lyte A solution containing EVs obtained from MSCs), intravenously, at intervals of 48 h. Placebo group: will consist of 5 participants who will receive an equal volume of Plasma-Lyte A, intravenously, following the same schedule as the IV group: two infusions with an interval of 48 hours.
Interventions
BIOLOGICALintravenous treatment with EVs
intravenous treatment with extracellular vesicles
BIOLOGICALintravenous treatment with placebo solution
intravenous treatment with placebo solution (without extracellular vesicles)
Sponsors
Hospital Sao Rafael
Rio de Janeiro State Research Supporting Foundation (FAPERJ)
Oswaldo Cruz Foundation
D'Or Institute for Research and Education
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The treatment and placebo solutions will be indistinguishable in terms of their appearance. Stringent protocols will be established to guarantee that the physicians responsible for assessing patient safety, evaluating efficacy outcomes, and conducting laboratory analyses will be blinded to the randomization codes.
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>= 18 years old; * Chest CT radiological image with ground-glass opacities or chest X-ray with - bilateral infiltrates characteristic of pulmonary edema; * In invasive mechanical ventilation with PEEP 5 cm H2O and PaO2/FiO2\<250mmHg; * Respiratory failure not explained by cardiac causes or fluid overload.
Exclusion criteria
* Unable to provide informed consent; * Pregnancy or breastfeeding; * Patients with active malignancy who have received chemotherapy in the last 2 years; * Life expectancy of less than 6 months or in exclusive palliative care; * Severe liver failure, with a Child-Pugh score \> 12; * Previous renal failure: patients already undergoing dialysis or patients with GFR \< 30ml/min/1.73 m2 * Clinical or radiological suspicion of tuberculosis; * Chronic respiratory failure; * Use of ECMO; * Moribund (high probability of death within the next 48 hours).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure administration of extracellular vesicles (EVs) up to 28 days | 28 days | Measure as reported adverse events up to 28 days after treatment or placebo administration to evaluate safety of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Variation in the Ratio PaO2/FiO2 | Baseline, day 01, day 02 and day 07 | PaO2 (arterial partial pressure of oxygen)/FiO2 (fraction of inspired oxygen) on the day of randomization and at 24 hours, 48 hours and 7 days after the first infusion; |
| Variation in the SOFA index | day 01, day 02, day 07, day 09, day 14 and day 29 | Variation in the SOFA index (Assessment of Sequential Organ Failure) at the time of randomization and during follow-up until discharge from the intensive care unit; |
| All-cause mortality | Day 14 and day 28 | at days 14 and 28 after randomization; |
| Duration of the period of hospitalization | 30 days | from hospital time in the intensive care unit (ICU) |
| Duration of the period of ICU ventilation | 30 days | If applicable,will be measured the time of mechanical ventilation. |
| Exploratory laboratory analysis | 30 days | variation in total and differential laboratory analysis. |
Countries
Brazil
Contacts
Primary ContactCarolina Nonaka, phD
Backup ContactIngrid Barbosa, B.Sc
Outcome results
None listed