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

Direct Biologics

Status and phase: Enrolling; Phase 3

Conditions: Acute Respiratory Distress Syndrome; ARDS

Treatments: Biological: ExoFlo; Other: Intravenous normal saline

Study type: Interventional

Funder types: Industry

Identifiers

NCT05354141

DB-EF-PHASEIII-0001

Details and patient eligibility

About

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).

Full 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).

Enrollment: 970 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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970 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Normal saline 100 mL

Treatment:

Other: Intravenous normal saline

Experimental Dose

Experimental group

Description:

Normal saline 85 mL and ExoFlo 15 mL

Treatment:

Biological: ExoFlo