Human Mesenchymal Stromal Cells For Acute Respiratory Distress Syndrome (START)

NCT ID: NCT02097641

Last Updated: 2019-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-15
• Study Completion Date: 2018-02-09

Brief Summary

This was a Phase 2a, randomized, double-blind, placebo-controlled, multi-center trial 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).

Detailed Description

We carried out a randomized, double-blind placebo-controlled trial of allogeneic bone marrow derived human mesenchymal stromal cells for treatment of moderate to severe ARDS in 60 patients, 40 MSC and 20 placebo, in a 2:1 randomization. This trial is the extension of the Phase 1 pilot trial (NCT01775774). Patients were followed daily for adverse events through day 28, death or hospital discharge, whichever occurs first. Vital status was collected at 6 and 12 months after study enrollment.

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 (hMSCs)

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

Group Type: EXPERIMENTAL

Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells

Intervention Type: BIOLOGICAL

Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells was administered intravenously over approximately 60-80 minutes.

Plasma-Lyte A (placebo)

A single dose of Plasma-Lyte A was administered intravenously over approximately 60-80 minutes.

Group Type: PLACEBO_COMPARATOR

Plasma-Lyte A

Intervention Type: BIOLOGICAL

Plasma-Lyte A placebo was administered intravenously over approximately 60-80 minutes.

Interventions

Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells

Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells was administered intravenously over approximately 60-80 minutes.

Intervention Type: BIOLOGICAL

Plasma-Lyte A

Plasma-Lyte A placebo was administered intravenously over approximately 60-80 minutes.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

Patients will be eligible for inclusion if they meet all of the below criteria. 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 < 200 with at least 8 cm H2O positive end-expiratory airway pressure (PEEP)

2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph

3. No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.

Exclusion Criteria

1. Age less than 18 years

2. Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS

3. Pregnant or breast-feeding

4. Prisoner

5. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years

6. Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%

7. Moderate to severe liver failure (Childs-Pugh Score > 12)

8. Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen

9. Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)

10. Major trauma in the prior 5 days

11. Lung transplant patient

12. No consent/inability to obtain consent

13. Moribund patient not expected to survive 24 hours

14. World Health Organization (WHO) Class III or IV pulmonary hypertension

15. Documented deep venous thrombosis or pulmonary embolism within past 3 months

16. No arterial line/no intent to place an arterial line

17. No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol

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

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

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

Ohio State University

OTHER

Sponsor Role: collaborator

Michael A. Matthay

OTHER

Sponsor Role: lead

Responsible Party

Michael A. Matthay

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael A Matthay, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California San Francisco

San Francisco, California, United States

Stanford University

Stanford, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Minnesota Medical Center

Saint Paul, Minnesota, United States

Ohio State University

Columbus, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Matthay MA, Calfee CS, Zhuo H, Thompson BT, Wilson JG, Levitt JE, Rogers AJ, Gotts JE, Wiener-Kronish JP, Bajwa EK, Donahoe MP, McVerry BJ, Ortiz LA, Exline M, Christman JW, Abbott J, Delucchi KL, Caballero L, McMillan M, McKenna DH, Liu KD. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Respir Med. 2019 Feb;7(2):154-162. doi: 10.1016/S2213-2600(18)30418-1. Epub 2018 Nov 16.

Reference Type: RESULT

PMID: 30455077 (View on PubMed)

Wick KD, Leligdowicz A, Zhuo H, Ware LB, Matthay MA. Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS. JCI Insight. 2021 Jun 22;6(12):e148983. doi: 10.1172/jci.insight.148983.

Reference Type: DERIVED

PMID: 33974564 (View on PubMed)

Liu KD, Wilson JG, Zhuo H, Caballero L, McMillan ML, Fang X, Cosgrove K, Calfee CS, Lee JW, Kangelaris KN, Gotts JE, Rogers AJ, Levitt JE, Wiener-Kronish JP, Delucchi KL, Leavitt AD, McKenna DH, Thompson BT, Matthay MA. Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome. Ann Intensive Care. 2014 Jul 3;4:22. doi: 10.1186/s13613-014-0022-z. eCollection 2014.

Reference Type: DERIVED

PMID: 25593740 (View on PubMed)

Asmussen S, Ito H, Traber DL, Lee JW, Cox RA, Hawkins HK, McAuley DF, McKenna DH, Traber LD, Zhuo H, Wilson J, Herndon DN, Prough DS, Liu KD, Matthay MA, Enkhbaatar P. Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia. Thorax. 2014 Sep;69(9):819-25. doi: 10.1136/thoraxjnl-2013-204980. Epub 2014 Jun 2.

Reference Type: DERIVED

PMID: 24891325 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1U01HL108713-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UCSF-hMSC-ARDS-P2

Identifier Type: -

Identifier Source: org_study_id