Clinical trial NCT06002841: Extracellular Vesicles From Mesenchymal Cells in the Treatment of Acute Respiratory Failure
Official title: Extracellular Vesicles From Mesenchymal Cells in the Treatment of Acute Respiratory Failure Associated With SARS-CoV-2 and Other Etiologies: a Clinical Trial, Randomized, Double-blind.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Severe Acute Respiratory Syndrome (SARS)
Acute Respiratory Distress Syndrome (ARDS)
Pneumonia
Keywords: SARS-CoV-2
intravenous therapy
extracellular vesicles
ARDS
mesenchymal cells
Lead sponsor: D'Or Institute for Research and Education
Sponsor class: OTHER
Collaborators: name: Hospital Sao Rafael
name: Rio de Janeiro State Research Supporting Foundation (FAPERJ)
name: Oswaldo Cruz Foundation
First posted: 2023-08-21
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Measure administration of extracellular vesicles (EVs) up to 28 days
timeFrame: 28 days
Secondary outcomes:
measure: All-cause mortality
timeFrame: Day 14 and day 28
measure: Variation in the Ratio PaO2/FiO2
timeFrame: Baseline, day 01, day 02 and day 07
measure: Variation in the SOFA index
timeFrame: day 01, day 02, day 07, day 09, day 14 and day 29
measure: Exploratory laboratory analysis
timeFrame: 30 days
measure: Duration of the period of hospitalization
timeFrame: 30 days
measure: Duration of the period of ICU ventilation
timeFrame: 30 days
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Hospital São Rafael
state: Bahia
Study officials:
affiliation: Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Brazil
name: Bruno Souza, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidade Federal do Rio de Janeiro (UFRJ)
name: Patrícia Rocco, M.D
role: PRINCIPAL_INVESTIGATOR
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