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

Sponsor

D'Or Institute for Research and Education (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06002841

Collaborator

Hospital Sao Rafael (Other), Rio de Janeiro State Research Supporting Foundation (FAPERJ) (Other), Oswaldo Cruz Foundation (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Acute Respiratory Syndrome (SARS) Acute Respiratory Distress Syndrome (ARDS) Pneumonia	Biological: intravenous treatment with EVs Biological: intravenous treatment with placebo solution	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel AssignmentParallel Assignment

Masking:

Double (Participant, 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.

Primary Purpose:

Treatment

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.

Anticipated Study Start Date :

Feb 1, 2024

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: intravenous treatment with EVs intravenous treatment with extracellular vesicles
Placebo Comparator: 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.	Biological: intravenous treatment with placebo solution intravenous treatment with placebo solution (without extracellular vesicles)

Arm

Intervention/Treatment

Experimental: 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.

Biological: intravenous treatment with EVs

intravenous treatment with extracellular vesicles

Placebo Comparator: 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.

Biological: intravenous treatment with placebo solution

intravenous treatment with placebo solution (without extracellular vesicles)

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

All-cause mortality [Day 14 and day 28]
at days 14 and 28 after randomization;
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;
Exploratory laboratory analysis [30 days]
variation in total and differential laboratory analysis.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital São Rafael	Salvador	Bahia	Brazil	41253-190

Sponsors and Collaborators

D'Or Institute for Research and Education
Hospital Sao Rafael
Rio de Janeiro State Research Supporting Foundation (FAPERJ)
Oswaldo Cruz Foundation

Investigators

Principal Investigator: Bruno Souza, M.D, Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Brazil
Principal Investigator: Patrícia Rocco, M.D, Universidade Federal do Rio de Janeiro (UFRJ)