Acute Respiratory Distress SyndromePhase 3NCT05354141
Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS)
A Phase 3 study testing ExoFlo and Intravenous normal saline in people with Acute Respiratory Distress Syndrome and ARDS, run by Direct Biologics, LLC at 32 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome, ARDS
- What is being tested?
- ExoFlo and Intravenous normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 970 participants
- Where
- 32 sitesUnited States
- Study dates
- 1 Jul 2022to 31 Dec 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 18-75 years of age
- Presence of the following criteria for moderate to severe ARDS as defined by the Berlin Criteria within 24 hours of the first infustion:
- Onset within 7 days of known clinical insult or requiring increasing respiratory rate, increasing oxygen flows, or increased work of breathing, and
- Bilateral lung opacities not fully explained by pleural effusions, atelectasis, or nodules, and
- PaO2/FiO2 (P/F ratio) ≤ 200 mm Hg, and
- 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
- Respiratory failure not fully explained by cardiac failure or fluid overload.
Who cannot join
- Lack of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
- Stated unwillingness to comply with all study procedures and availability for the duration of the study
- Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
- Active malignancy requiring treatment within the last two years, with the exception of non-melanoma skin cancers.
- 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.
- Duration of mechanical ventilation exceeds 3 days or 72 hours from diagnosis of ARDS.
Show all 14Show fewer
- ALT or AST > 8 x Upper Limit of Normal (ULN).
- Documented history of cirrhosis.
- DNR order, as in electing not to receive chest compressions, cardiac defibrillation, cardiac drugs, or intubation.
- Moribund-expected survival < 24 hours.
- Severe metabolic disturbances at randomization (e.g., ketoacidosis, pH < 7.2)
- Patient currently connected to Extracorporeal Membrane Oxygenation at initiation of screening.
- 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
- Use of investigational COVID-19 agents or any other investigational agents within 30 days prior to the first dose.
Trial locations and contacts
32 sites in 1 country. Contact the study team or a site near you to ask about taking part.
32 sites in 1 country
United States32 sites, 32 recruiting
- Recruiting
Direct Biologics Investigational Site
Boise, Idaho, 83712
- Recruiting
Direct Biologics Investigational Site
Boston, Massachusetts, 02115
- Recruiting
Direct Biologics Investigational Site
Burlington, Massachusetts, 01805
- Recruiting
Direct Biologics Investigational Site
Charleston, South Carolina, 29425
- Recruiting
Direct Biologics Investigational Site
Cincinnati, Ohio, 45219
- Recruiting
Direct Biologics Investigational Site
Cleveland, Ohio, 44106
- Recruiting
Direct Biologics Investigational Site
Dallas, Texas, 75246
- Recruiting
Direct Biologics Investigational Site
Davis, California, 95817
- Recruiting
Direct Biologics Investigational Site
Detroit, Michigan, 48202
- Recruiting
Direct Biologics Investigational Site
Durham, North Carolina, 27710
- Recruiting
Direct Biologics Investigational Site
Flushing, New York, 11368
- Recruiting
Direct Biologics Investigational Site
Fort Worth, Texas, 76104
- Recruiting
Direct Biologics Investigational Site
Houston, Texas, 77030
- Recruiting
Direct Biologics Investigational Site
Iowa City, Iowa, 52242
- Recruiting
Direct Biologics Investigational Site
Irvine, California, 92627
- Recruiting
Direct Biologics Investigational Site
Jackson, Mississippi, 39202
- Recruiting
Direct Biologics Investigational Site
Jacksonville, Florida, 32224
- Recruiting
Direct Biologics Investigational Site
Knoxville, Tennessee, 37996
- Recruiting
Direct Biologics Investigational Site
Little Rock, Arkansas, 72205
- Not yet recruiting
Direct Biologics Investigational Site
Murray, Utah, 84107
- Recruiting
Direct Biologics Investigational Site
Nashville, Tennessee, 37235
- Recruiting
Direct Biologics Investigational Site
Phoenix, Arizona, 85012
- Recruiting
Direct Biologics Investigational Site
Portland, Oregon, 97239
- Recruiting
Direct Biologics Investigational Site
Queens, New York, 11040
- Recruiting
Direct Biologics Investigational Site
Rochester, Minnesota, 55905
- Recruiting
Direct Biologics Investigational Site
Sacramento, California, 95817
- Recruiting
Direct Biologics Investigational Site
Salt Lake City, Utah, 84101
- Recruiting
Direct Biologics Investigational Site
Silver Spring, Maryland, 20910
- Recruiting
Direct Biologics Investigational Site
Springfield, Massachusetts, 01199
- Recruiting
Direct Biologics Investigational Site
The Bronx, New York, 10467
- Recruiting
Direct Biologics Investigational Site
Washington D.C., District of Columbia, 20010
- Recruiting
Direct Biologics Investigational Site
Winston-Salem, North Carolina, 27157
About this study
Official title: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles for Hospitalized Patients With Moderate-to-Severe ARDS: A Phase III Clinical Trial
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).
Read the 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).
- Conditions
- Acute Respiratory Distress Syndrome, ARDS
- Being tested
- ExoFlo, Intravenous normal saline
- Keywords
- ExoFlo, Extracellular Vesicles, Exosome, ARDS
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExoFloBiological
Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles
Intravenous normal salineOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Normal saline 100 mL Receives: Other: Intravenous normal saline |
| Experimental Dose | Experimental | Normal saline 85 mL and ExoFlo 15 mL Receives: Biological: ExoFlo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of 60-day All-cause Mortality
To evaluate the 60-day mortality rate for IMP 15mL as a treatment for moderate-to-severe ARDS compared to placebo. Reducing the mortality rate for hospitalized patients with moderate-to-severe ARDS is a measure of the treatment effect.
Measured: 60 days
Secondary outcomes (5)
Time to death
Reducing the mortality rate for hospitalized patients moderate-to-severe ARDS is a measure of the treatment effect.
Measured: 60 days
Ventilator-free days (VFDs)
Number of days for which patients are not on mechanical ventilation.
Measured: Day 29
Oxygen free days
Number of days for which patients are not on oxygen support.
Measured: Day 29
ICU free days
Number of days for which patients are not in the ICU.
Measured: Day 29
Incidence of Treatment Emergent Serious Adverse Events (TESAEs)
Safety comparison performed between IMP 15 mL and placebo arms
Measured: 61 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2022
- Study start1 Jul 2022
- Primary completion30 Nov 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, randomized, double-blinded, placebo-controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 970 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Direct Biologics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bill Arana, Study director, Direct Biologics, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05354141
- Sponsor's protocol ID
- DB-EF-PHASEIII-0001
- Status last verified
- Feb 2026
- First submitted
- 27 Apr 2022
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles for Hospitalized Patients With Moderate-to-Severe ARDS: A Phase III Clinical Trial
- ClinicalTrials.gov ID
- NCT05354141
- Acronym / sponsor ID
- DB-EF-PHASEIII-0001
- Conditions
- Acute Respiratory Distress Syndrome, ARDS
- Keywords
- ExoFlo, Extracellular Vesicles, Exosome, ARDS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 970 participants (estimated)
- Lead sponsor
- Direct Biologics, LLCIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 29 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Multicenter, randomized, double-blinded, placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Intravenous normal salineNormal saline 100 mL |
| Experimental Dose | Experimental | Biological: ExoFloNormal saline 85 mL and ExoFlo 15 mL |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Men and women aged 18-75 years of age
- Presence of the following criteria for moderate to severe ARDS as defined by the Berlin Criteria within 24 hours of the first infustion:
Key exclusion criteria (14 listed)
- Lack of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
- Stated unwillingness to comply with all study procedures and availability for the duration of the study
- Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
- Active malignancy requiring treatment within the last two years, with the exception of non-melanoma skin cancers.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ExoFloIntravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles | Biological | Experimental Dose |
| Intravenous normal salinePlacebo | Other | Placebo |
Primary outcome
Evaluation of 60-day All-cause Mortality
Time frame: 60 days
To evaluate the 60-day mortality rate for IMP 15mL as a treatment for moderate-to-severe ARDS compared to placebo. Reducing the mortality rate for hospitalized patients with moderate-to-severe ARDS is a measure of the treatment effect.
5 secondary outcomes
Time to death
Time frame: 60 days
Ventilator-free days (VFDs)
Time frame: Day 29
Oxygen free days
Time frame: Day 29
ICU free days
Time frame: Day 29
Incidence of Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: 61 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2026.
- Direct Biologics, LLCLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Acute Respiratory Distress Syndrome
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
Not yet recruitingObservational study
Development and Multicenter Validation of an Explainable System for Neonatal ARDS-Compatible Phenotyping
Acute Respiratory Distress Syndrome
RecruitingObservational study
Assessment of Blood Viscosity in ARDS (Acute Respiratory Distress Syndrome)
ARDS
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bill Arana study director
Direct Biologics, LLC
32 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ExoFlo and Intravenous normal saline in people with Acute Respiratory Distress Syndrome and ARDS, run by Direct Biologics, LLC at 32 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bill Arana (1-800-791-1021, clinicalaffairs@directbiologics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of 60-day All-cause Mortality (time frame: 60 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.