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Extracellular Vesicles From Mesenchymal Cells in the Treatment of Acute Respiratory Failure

Phase 1
Not yet recruiting
Conditions
Severe Acute Respiratory Syndrome (SARS)
Pneumonia
Acute Respiratory Distress Syndrome (ARDS)
Interventions
Biological: intravenous treatment with EVs
Biological: intravenous treatment with placebo solution
Registration Number
NCT06002841
Lead Sponsor
D'Or Institute for Research and Education
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
15
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
EV groupintravenous treatment with EVswill 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 groupintravenous treatment with placebo solutionwill 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.
Primary Outcome Measures
NameTimeMethod
Measure administration of extracellular vesicles (EVs) up to 28 days28 days

Measure as reported adverse events up to 28 days after treatment or placebo administration to evaluate safety of treatment

Secondary Outcome Measures
NameTimeMethod
Variation in the SOFA indexday 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;

Variation in the Ratio PaO2/FiO2Baseline, 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;

Duration of the period of hospitalization30 days

from hospital time in the intensive care unit (ICU)

All-cause mortalityDay 14 and day 28

at days 14 and 28 after randomization;

Exploratory laboratory analysis30 days

variation in total and differential laboratory analysis.

Duration of the period of ICU ventilation30 days

If applicable,will be measured the time of mechanical ventilation.

Trial Locations

Locations (1)

Hospital São Rafael

🇧🇷

Salvador, Bahia, Brazil

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