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

Respiratory Distress Syndrome, Adult Clinical Trial

— START  

Official title:

Prospective, Randomized, Multi-center Phase 2 Clinical Trial of Allogeneic Bone Marrow-derived Human Mesenchymal Stromal Cells (hMSCs) for the Treatment of Acute Respiratory Distress Syndrome (ARDS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02097641
• Other study ID #: UCSF-hMSC-ARDS-P2
• Secondary ID: 1U01HL108713-01
• Status: Completed
• Phase: Phase 2
• Start date: March 15, 2014
• Est. completion date: February 9, 2018

Study information

• Verified date: March 2019
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 9, 2018
• Est. primary completion date: March 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Lung Injury
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Biological:
• Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells
Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells was administered intravenously over approximately 60-80 minutes.
• Plasma-Lyte A
Plasma-Lyte A placebo was administered intravenously over approximately 60-80 minutes.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ohio State University	Columbus	Ohio
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Minnesota Medical Center	Saint Paul	Minnesota
United States	University of California San Francisco	San Francisco	California
United States	Stanford University	Stanford	California

Sponsors (7)

Lead Sponsor	Collaborator
Michael A. Matthay	Massachusetts General Hospital, National Heart, Lung, and Blood Institute (NHLBI), Ohio State University, Stanford University, University of Minnesota - Clinical and Translational Science Institute, University of Pittsburgh

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 wit — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numbers of Patients Occurred Pre-specified Infusion Associated Events Occurring Within 6 Hours of Study Infusion	Within 6 h of study product infusion: Increase in vasopressor dose to the following values or higher: Norepinephrine 10 µg/min; Phenylephrine 100 µg/min; Dopamine 10 µg/kg per min; Epinephrine 0.1 µg/kg per min or addition of a third vasopressor; New ventricular tachycardia, ventricular fibrillation or asystole; New cardiac arrhythmia requiring cardioversion; Hypoxaemia requiring an increase in FiO2 of 0·2 or more and an increase in PEEP of 5·0 or more to maintain SpO2 in the target range of 88-95%; Clinical scenario consistent with transfusion incompatibility or transfusion-related infection (eg, urticaria, new bronchospasm)	6 hours
Primary	Numbers of Patients Occurred Any Cardiac Arrest or Death Within 24 Hours of Study Infusion	Within 24 h of study product infusion; • Any cardiac arrest or death	24 hours
Primary	Numbers of Patients Occurred Any Unexpected Severe Adverse Events (Including All-cause Deaths)	Safety endpoint: Any unexpected severe adverse events in two groups	12 months
Secondary	PaO2:FiO2 Change From Baseline to Day 3	Efficacy endpoint: PaO2:FiO2 change from baseline to day 3	baseline and day 3
Secondary	Lung Injury Score From Baseline to Day 3	Murray score for acute lung injury. The range is 0 to 4. The higher score, the worst outcome.	baseline and day 3
Secondary	Oxygenation Index Change From Baseline to Day 2	Oxygenation index with the following validated measure of respiratory function: FiO2 (%) x mean airway pressure / PaO2	baseline and day 2
Secondary	SOFA Score Change From Baseline to Day 3	Sequential organ failure assessment score (SOFA). The SOFA score ranges from 0 to 24. The higher, the worse.	baseline and day 3
Secondary	Number of Patients Death to Day 28	Efficacy endpoint: all-cause mortality at day 28	28 days
Secondary	Mortality to Day 60	Efficacy endpoint: all-cause mortality at day 60	60 days
Secondary	Number of Ventilator-free Days to Day 28	Efficacy endpoint: Number of ventilator-free days to day 28.	28 days
Secondary	Non-pulmonary Organ-failure-free Days to Day 28	Efficacy endpoint: Non-pulmonary organ-failure-free days to day 28	28 days
Secondary	Angiopoietin 2 Change From Baseline to 6 h	Biological markers of endothelial injury: angiopoietin 2	baseline and 6 hours
Secondary	Angiopoietin 2 Change From Baseline to 24 h	Biological markers of endothelial injury: angiopoietin 2	baseline and 24 hours
Secondary	Interleukin 6 Change From Baseline to 6 h	Biological markers of inflammation: interleukin 6	baseline and 6 hours
Secondary	Interleukin 6 Change From Baseline to 24 h	Biological markers of inflammation: interleukin 6	baseline and 24 hours
Secondary	Interleukin 8 Change From Baseline to 6 h	Biological markers of inflammation: interleukin 8	baseline and 6 hours
Secondary	Interleukin 8 Change From Baseline to 24 h	Biological markers of inflammation: interleukin 8	baseline and 24 hours
Secondary	RAGE Change From Baseline to 6 h	Biological markers of alveolar epithelial injury: receptor for advanced glycation end products (RAGE)	baseline and 6 hours
Secondary	RAGE Change From Baseline to 24 h	Biological markers of alveolar epithelial injury: receptor for advanced glycation end products (RAGE)	baseline and 24 hours