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NCT05354141PHASE3Recruiting

Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS)

Direct Biologics, LLC

Start Date

7/1/2022

Completion Date

12/31/2027

Summary

To evaluate the safety and efficacy of intravenous (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles (EVs), ExoFlo, versus placebo for the treatment of hospitalized patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).

Detailed Description

This is a Phase III, multicenter, randomized, double-blinded, placebo-controlled trial for the treatment of moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).

Eligibility Criteria

Age Range: 18 years to 75 years

Inclusion Criteria: 1. Men and women aged 18-75 years of age 2. Presence of the following criteria for moderate to severe ARDS as defined by the Berlin Criteria within 24 hours of the first infustion: 1. Onset within 7 days of known clinical insult or requiring increasing respiratory rate, increasing oxygen flows, or increased work of breathing, and 2. Bilateral lung opacities not fully explained by pleural effusions, atelectasis, or nodules, and 3. PaO2/FiO2 (P/F ratio) ≤ 200 mm Hg, and 4. Invasive or noninvasive ventilation with a minimum PEEP 5 cm H2O or minimum of continuous positive airway pressure (CPAP) 5 cm H2O, or High Flow Nasal Oxygen at ≥ 30 L/min, and 5. Respiratory failure not fully explained by cardiac failure or fluid overload. Exclusion Criteria: 1. Lack of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy). 2. Stated unwillingness to comply with all study procedures and availability for the duration of the study 3. Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent. 4. Active malignancy requiring treatment within the last two years, with the exception of non-melanoma skin cancers. 5. Major physical trauma in the last 2 days, including motor vehicle accidents, assaults, mechanical falls with sequelae of significant bleeding or craniofacial bruising, and surgeries, such that not one or more injury may be undiagnosed at time of screening. 6. Duration of mechanical ventilation exceeds 3 days or 72 hours from diagnosis of ARDS. 7. ALT or AST \> 8 x Upper Limit of Normal (ULN). 8. Documented history of cirrhosis. 9. DNR order, as in electing not to receive chest compressions, cardiac defibrillation, cardiac drugs, or intubation. 10. Moribund-expected survival \< 24 hours. 11. Severe metabolic disturbances at randomization (e.g., ketoacidosis, pH \< 7.2) 12. Patient currently connected to Extracorporeal Membrane Oxygenation at initiation of screening. 13. If the candidate, either a male or female of reproductive potential, is unwilling to two methods of highly effective birth control contraception such as condoms with oral contraceptive pill or choose to remain abstinent if already practicing abstinence during the screening period. The required duration of usage of double method OR maintenance of abstinence must include the time from the beginning of the screening period until Day 61, day of withdrawal or early termination 14. Use of investigational COVID-19 agents or any other investigational agents within 30 days prior to the first dose.

Interventions

BIOLOGICAL

ExoFlo

OTHER

Intravenous normal saline

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Conditions

Acute Respiratory Distress SyndromeARDS

Locations

Direct Biologics Investigational Site

Phoenix, Arizona 85012

United States

Direct Biologics Investigational Site

Little Rock, Arkansas 72205

United States

Direct Biologics Investigational Site

Davis, California 95817

United States

Direct Biologics Investigational Site

Irvine, California 92627

United States

Direct Biologics Investigational Site

Sacramento, California 95817

United States

Direct Biologics Investigational Site

Washington D.C., District of Columbia 20010

United States

Direct Biologics Investigational Site

Jacksonville, Florida 32224

United States

Direct Biologics Investigational Site

Boise, Idaho 83712

United States

Direct Biologics Investigational Site

Iowa City, Iowa 52242

United States

Direct Biologics Investigational Site

Silver Spring, Maryland 20910

United States

Direct Biologics Investigational Site

Boston, Massachusetts 02115

United States

Direct Biologics Investigational Site

Burlington, Massachusetts 01805

United States

Direct Biologics Investigational Site

Springfield, Massachusetts 01199

United States

Direct Biologics Investigational Site

Detroit, Michigan 48202

United States

Direct Biologics Investigational Site

Rochester, Minnesota 55905

United States

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Jackson, Mississippi 39202

United States

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Flushing, New York 11368

United States

Direct Biologics Investigational Site

Queens, New York 11040

United States

Direct Biologics Investigational Site

The Bronx, New York 10467

United States

Direct Biologics Investigational Site

Durham, North Carolina 27710

United States

Direct Biologics Investigational Site

Winston-Salem, North Carolina 27157

United States

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Cincinnati, Ohio 45219

United States

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Cleveland, Ohio 44106

United States

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Portland, Oregon 97239

United States

Direct Biologics Investigational Site

Charleston, South Carolina 29425

United States

Direct Biologics Investigational Site

Knoxville, Tennessee 37996

United States

Direct Biologics Investigational Site

Nashville, Tennessee 37235

United States

Direct Biologics Investigational Site

Dallas, Texas 75246

United States

Direct Biologics Investigational Site

Fort Worth, Texas 76104

United States

Direct Biologics Investigational Site

Houston, Texas 77030

United States

Direct Biologics Investigational Site

Murray, Utah 84107

United States

Direct Biologics Investigational Site

Salt Lake City, Utah 84101

United States