Mesenchymal Stromal Cells For Acute Respiratory Distress Syndrome

NCT ID: NCT03818854

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-26
• Study Completion Date: 2024-06-30

Brief Summary

This is a Phase 2b, randomized, double-blind, placebo-controlled, multi-center study to assess the safety and efficacy of a single dose of Allogeneic Bone Marrow-derived Human Mesenchymal Stromal Cells (hMSCs) infusion in patients with Acute Respiratory Distress Syndrome (ARDS). This study is the extension of the Phase 1 pilot study (NCT01775774) and Phase 2a study (NCT02097641).

Detailed Description

This clinical study design is a randomized, double-blinded, placebo-controlled Phase 2b clinical trial using a 10 million cell/kg dose of human Mesenchymal Stromal Cells (hMSCs). Subjects will be randomized in a 1:1 randomization scheme to receive hMSCs or cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) as the placebo; the study will enroll 120 patients who achieve a stable clinical baseline and receive study product (either hMSCs or the placebo).

The Data and Safety Monitoring Board (DSMB) will review adverse outcomes and protocol compliance. A pre-specified interim review will occur after 60 subjects have been enrolled and received study product; enrollment will continue during the DSMB review. All pre-specified clinically important events and unexpected serious adverse events including death during hospitalization up to 60 days will be reported to the DSMB on an ongoing basis; the study will be stopped for a safety evaluation by the DSMB if they have any concerns or if three subjects have pre-specified clinically important events or unexpected serious adverse events except death since death will be common in this critically ill population due the nature of the underlying illness (e.g., ARDS).

Conditions

Respiratory Distress Syndrome, Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Human Mesenchymal Stromal Cells

A single dose of 10 million cells/kg predicted body weight (PBW) Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells will administered intravenously over approximately 60-80 minutes.

Group Type: EXPERIMENTAL

Human Mesenchymal Stromal Cells

Intervention Type: BIOLOGICAL

Immediately prior to administration, the study product will be thawed and diluted 1:1 with reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40). Additional reconstitution media is added to a final product volume of 300 mL.

Cell Reconstitution Media

A single dose of cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) will administered intravenously over approximately 60-80 minutes.

Group Type: EXPERIMENTAL

Cell Reconstitution Media

Intervention Type: BIOLOGICAL

300 mL of reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40)

Interventions

Human Mesenchymal Stromal Cells

Immediately prior to administration, the study product will be thawed and diluted 1:1 with reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40). Additional reconstitution media is added to a final product volume of 300 mL.

Intervention Type: BIOLOGICAL

Cell Reconstitution Media

300 mL of reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40)

Intervention Type: BIOLOGICAL

Other Intervention Names

hMSCs; Placebo

Eligibility Criteria

Inclusion Criteria

Patients will be eligible for inclusion if they meet all of the below criteria within 14 days of initial ICU admission. Criteria 1-3 must all be present within a 24-hour time period and at the time of enrollment:

Acute onset (defined below) of:

1. A need for positive pressure ventilation by an endotracheal or tracheal tube with a PaO2/FiO2 ratio <250 mmHg and ≥5 cm H2O positive end-expiratory airway pressure (PEEP), as per the Berlin Criteria.

2. Bilateral infiltrates consistent with pulmonary edema (defined below) on the frontal chest radiograph, or bilateral ground glass opacities on a chest CT scan.

3. No clinical evidence of left atrial hypertension as a primary explanation for the bilateral pulmonary infiltrates.

1. Hypotension (systolic blood pressure[SBP] < 90 mmHg) in the field or in the first 24 h after injury, or

2. Transfusion of 3 units of blood products in the first 24 hours following injury, or

3. Meets the new Critical Administration Threshold (CAT) criteria with at least 3 units of blood in one hour, or

4. Blunt or penetrating torso trauma, or

5. Long bone fractures, or

6. The highest level of institutional trauma activation

Exclusion Criteria

1. Age less than 18 years

2. Greater than 72 hours since first meeting ARDS criteria per the Berlin definition of ARDS

3. Greater than 14 days since initial ICU admission

4. Inability to administer study product within 14 days of ICU admission

5. PaO2/FiO2 ≥ 250 mmHg after consent obtained and before study product is administered

6. Unable to obtain informed consent/no surrogate available

7. Pregnant or lactating

8. In custody of law enforcement officials

9. Burns > 20% of total body surface area

10. WHO Class III or IV pulmonary hypertension

11. History of cancer treatment in the last 2 years except for non-melanotic skin cancers

12. Underlying medical condition for which 6-month mortality is estimated to be > 50%

13. Moribund patient not expected to survive 24 hours

14. Advanced chronic liver disease (Child-Pugh Score > 12)

15. Severe chronic respiratory disease with the use of home oxygen

16. Severe traumatic brain injury - defined as:

1. A patient who has undergone intracranial neurosurgical intervention for monitoring or therapy (intracranial pressure monitoring, external ventricular drain, craniotomy), or

2. Intracranial injury by head CT (does not include patients with minimal subarachnoid injury and/or minor skull fracture), or

3. Post-resuscitation Glasgow Coma Score (GCS) < 9 assessed after sedation interruption, or

4. Non-survivable head injury as assessed by neurosurgery

17. Evidence of anoxic brain injury

18. History of stroke within the last 3 years

19. No intent/unwillingness to follow lung protective ventilation strategy

20. Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)

21. Anticipated extubation within 24 hours of enrollment

22. Clinical evidence of left atrial hypertension as measured by a pulmonary arterial wedge pressure > 18mmHg or left ventricular failure measured by an echocardiogram with a left ventricular ejection fraction less than 40%. Clinical judgement will determine if either of these measurements needs to be carried out.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Michael A. Matthay

OTHER

Sponsor Role: lead

United States Department of Defense

FED

Sponsor Role: collaborator

Harborview Injury Prevention and Research Center

OTHER

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

Responsible Party

Michael A. Matthay

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael Matthay, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California Davis Medical Center

Sacramento, California, United States

Zuckerberg San Francisco General Hospital and Trauma Center

San Francisco, California, United States

University of California San Francisco

San Francisco, California, United States

Oregon Health & Science University

Portland, Oregon, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Memorial Hermann Hospital - Texas Medical Center

Houston, Texas, United States

Harborview Medical Center

Seattle, Washington, United States

Countries

United States

References

Matthay MA, Zhou H, Sarma A, Alipanah-Lechner N, Hendrickson C, Kornblith LZ, Schreiber M, Zonies D, Khan A, Robinson B, Johnson NJ, Ware LB, Guillamondegui O, Casey J, Moore L, Patel B, Kao L, Wade CE, Fox E, Cox C, Khawanja F, Aguillon Prada R, Hossri S, Callcut R, Albertson T, Delucchi KL, McMillan M, Langelier CR, Pati S, McKenna DH, Leroux C, Calfee CS, Liu KD. Treatment with Allogenic Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome: A Double-Blind, Placebo-controlled, Multi-Center, Phase 2b Clinical Trial (STAT). Am J Respir Crit Care Med. 2025 Jul 29:10.1164/rccm.202411-2254OC. doi: 10.1164/rccm.202411-2254OC. Online ahead of print.

Reference Type: DERIVED

PMID: 40728562 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

UCSF-hMSC-ARDS-P1P2-12

Identifier Type: -

Identifier Source: org_study_id