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

Primary Purpose

Severe Acute Respiratory Syndrome (SARS), Acute Respiratory Distress Syndrome (ARDS), Pneumonia

Status
Not yet recruiting
Phase
Phase 1
Locations
Brazil
Study Type
Interventional
Intervention
intravenous treatment with EVs
intravenous treatment with placebo solution
Sponsored by
D'Or Institute for Research and Education
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Acute Respiratory Syndrome (SARS) focused on measuring SARS-CoV-2, intravenous therapy, extracellular vesicles, ARDS, mesenchymal cells

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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).

Sites / Locations

  • Hospital São Rafael

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

EV group

Placebo group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Measure administration of extracellular vesicles (EVs) up to 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
at days 14 and 28 after randomization;
Variation in the Ratio PaO2/FiO2
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
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
variation in total and differential laboratory analysis.
Duration of the period of hospitalization
from hospital time in the intensive care unit (ICU)
Duration of the period of ICU ventilation
If applicable,will be measured the time of mechanical ventilation.

Full Information

First Posted
July 27, 2023
Last Updated
August 18, 2023
Sponsor
D'Or Institute for Research and Education
Collaborators
Hospital Sao Rafael, Rio de Janeiro State Research Supporting Foundation (FAPERJ), Oswaldo Cruz Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT06002841
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 1, 2024 (Anticipated)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
D'Or Institute for Research and Education
Collaborators
Hospital Sao Rafael, Rio de Janeiro State Research Supporting Foundation (FAPERJ), Oswaldo Cruz Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Acute Respiratory Syndrome (SARS), Acute Respiratory Distress Syndrome (ARDS), Pneumonia
Keywords
SARS-CoV-2, intravenous therapy, extracellular vesicles, ARDS, mesenchymal cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Parallel Assignment
Masking
ParticipantInvestigator
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.
Allocation
Randomized
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EV group
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
intravenous treatment with EVs
Intervention Description
intravenous treatment with extracellular vesicles
Intervention Type
Biological
Intervention Name(s)
intravenous treatment with placebo solution
Intervention Description
intravenous treatment with placebo solution (without extracellular vesicles)
Primary Outcome Measure Information:
Title
Measure administration of extracellular vesicles (EVs) up to 28 days
Description
Measure as reported adverse events up to 28 days after treatment or placebo administration to evaluate safety of treatment
Time Frame
28 days
Secondary Outcome Measure Information:
Title
All-cause mortality
Description
at days 14 and 28 after randomization;
Time Frame
Day 14 and day 28
Title
Variation in the Ratio PaO2/FiO2
Description
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;
Time Frame
Baseline, day 01, day 02 and day 07
Title
Variation in the SOFA index
Description
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;
Time Frame
day 01, day 02, day 07, day 09, day 14 and day 29
Title
Exploratory laboratory analysis
Description
variation in total and differential laboratory analysis.
Time Frame
30 days
Title
Duration of the period of hospitalization
Description
from hospital time in the intensive care unit (ICU)
Time Frame
30 days
Title
Duration of the period of ICU ventilation
Description
If applicable,will be measured the time of mechanical ventilation.
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carolina Nonaka, phD
Phone
+55 (71) 3281-6970
Email
carolina.nonaka@hsr.com.br
First Name & Middle Initial & Last Name or Official Title & Degree
Ingrid Barbosa, B.Sc
Phone
+551121098855
Email
nape@idor.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Souza, M.D
Organizational Affiliation
Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Brazil
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Patrícia Rocco, M.D
Organizational Affiliation
Universidade Federal do Rio de Janeiro (UFRJ)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital São Rafael
City
Salvador
State/Province
Bahia
ZIP/Postal Code
41253-190
Country
Brazil
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolina Nonaka, phD
Phone
+55 (71) 3281-6970
Email
carolina.nonaka@hsr.com.br
First Name & Middle Initial & Last Name & Degree
Tânia Aravena, B.Sc
Phone
+55 (71) 98748-6532
Email
tania.mariela@hsr.com.br
First Name & Middle Initial & Last Name & Degree
Bruno Souza, M.D
First Name & Middle Initial & Last Name & Degree
Patricia Rocco, M.D

12. IPD Sharing Statement

Plan to Share IPD
No
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Extracellular Vesicles From Mesenchymal Cells in the Treatment of Acute Respiratory Failure

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