Trial Outcomes & Findings for Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome (NCT NCT01775774)

Last Updated: 2017-08-14

Results Overview

Any of the following occurring within 6 h of mesenchymal stem-cell infusion: * Addition of a third vasopressor or an increase in vasopressor dose greater than or equal to the following: * Norepinephrine: 10 μg per min * Phenylephrine: 100 μg per min * Dopamine: 10 μg/kg per min * Epinephrine: 0·1 μg/kg per min * Hypoxaemia requiring an increase in the fraction of inspired oxygen of ≥0·2 and increase in positive end-expiratory airway pressure level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95% * New cardiac arrhythmia requiring cardioversion * New ventricular tachycardia, ventricular fi brillation, or asystole * A clinical scenario consistent with transfusion incompatibility or transfusion-related infection * Cardiac arrest or death within 24 h of mesenchymal stem-cell infusion

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

9 participants

Primary outcome timeframe

24 hours

Results posted on

2017-08-14

Participant Flow

This dose-escalation Phase 1 clinical trial with 3 cohorts with 3 subjects/cohort was performed in 7 centers in USA between July 2013 to January 2014.

Participant milestones

Participant milestones
Measure	Human Mesenchymal Stem Cells 1 Million Cells/kg PBW Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells 5 Million Cells/kg PBW Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells 10 Million Cells/kg PBW Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.
Overall Study STARTED	3	3	3
Overall Study COMPLETED	3	3	3
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Human Mesenchymal Stem Cells 1 Million Cells/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Mesenchymal Stem Cells 5 Million Cells/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Mesenchymal Stem Cells 10 Million Cells/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Age, Continuous	58.0 years n=5 Participants	58.3 years n=7 Participants	48.3 years n=5 Participants	54.9 years n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	9 participants n=4 Participants
APACHE III Score	91.7 scores on a scale n=5 Participants	89.7 scores on a scale n=7 Participants	88.3 scores on a scale n=5 Participants	89.9 scores on a scale n=4 Participants
Primary cause of ARDS Pneumonia	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	4 participants n=4 Participants
Primary cause of ARDS Aspiration	1 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Primary cause of ARDS Sepsis	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Primary cause of ARDS Pre-eclampsia	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants

PRIMARY outcome

Timeframe: 24 hours

Outcome measures

Outcome measures
Measure	Human Mesenchymal Stem Cells: 1 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 5 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 10 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.
Incidence of Pre-specified Infusion Associated Adverse Events	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first.

The number of participants with a severe adverse event during the study was assessed.

Outcome measures

Outcome measures
Measure	Human Mesenchymal Stem Cells: 1 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 5 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 10 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.
Incidence of Severe Adverse Events (SAEs)	2 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: time of initiating unassisted breathing to day 28

Ventilator Free Days (VFDs) to day 28 were defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a subject received assisted breathing at day 27 or died prior to day 28, a value of zero VFDs was given.

Outcome measures

Outcome measures
Measure	Human Mesenchymal Stem Cells: 1 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 5 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 10 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.
Ventilator Free Days at Study Day 28	18 day Interval 0.0 to 24.0	22 day Interval 0.0 to 27.0	20 day Interval 12.0 to 26.0

SECONDARY outcome

Timeframe: 28 days

Days on vasopressor to day 28 after study enrollment

Outcome measures

Outcome measures
Measure	Human Mesenchymal Stem Cells: 1 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 5 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 10 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.
Duration of Vasopressor Use (Days)	4 day Interval 0.0 to 10.0	2 day Interval 0.0 to 3.0	0 day Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 28 days after study enrollment

Outcome measures

Outcome measures
Measure	Human Mesenchymal Stem Cells: 1 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 5 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 10 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.
ICU Free Days to Day 28	14 day Interval 0.0 to 24.0	21 day Interval 0.0 to 26.0	18 day Interval 9.0 to 22.0

SECONDARY outcome

Timeframe: 60 days after randomization

The number of subjects alive at study day 60. Those subjects discharged home prior to day 60 were counted as alive at day 60.

Outcome measures

Outcome measures
Measure	Human Mesenchymal Stem Cells: 1 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 5 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 10 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.
Hospital Survival to Day 60	2 participants	2 participants	3 participants

SECONDARY outcome

Timeframe: From study enrollment to Hospital discharge

The number of patients expired at hospital discharge.

Outcome measures

Outcome measures
Measure	Human Mesenchymal Stem Cells: 1 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 5 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.	Human Mesenchymal Stem Cells: 10 Million Cellls/kg PBW n=3 Participants Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells were administered intravenously into the 3 planned dosing cohorts.
Mortality at Hospital Discharge	1 participants	1 participants	0 participants

Adverse Events

Human Mesenchymal Stem Cells: 1 Million Cells/kg PBW

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Human Mesenchymal Stem Cells: 5 Million Cells/kg PBW

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Human Mesenchymal Stem Cells: 10 Million Cells/kg PBW

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Human Mesenchymal Stem Cells: 1 Million Cells/kg PBW n=3 participants at risk Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.	Human Mesenchymal Stem Cells: 5 Million Cells/kg PBW n=3 participants at risk Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.	Human Mesenchymal Stem Cells: 10 Million Cells/kg PBW n=3 participants at risk Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.
Respiratory, thoracic and mediastinal disorders Multiorgan failure	33.3% 1/3 • 1 year	33.3% 1/3 • 1 year	0.00% 0/3 • 1 year
Vascular disorders Infarcts of kidneys, spleen and brain	33.3% 1/3 • 1 year	0.00% 0/3 • 1 year	0.00% 0/3 • 1 year

Other adverse events

Other adverse events
Measure	Human Mesenchymal Stem Cells: 1 Million Cells/kg PBW n=3 participants at risk Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.	Human Mesenchymal Stem Cells: 5 Million Cells/kg PBW n=3 participants at risk Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.	Human Mesenchymal Stem Cells: 10 Million Cells/kg PBW n=3 participants at risk Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.
Hepatobiliary disorders Elevated liver function tests	0.00% 0/3 • 1 year	33.3% 1/3 • 1 year	0.00% 0/3 • 1 year
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • 1 year	0.00% 0/3 • 1 year	33.3% 1/3 • 1 year

Additional Information

Michael A. Matthay, MD

University of California San Francisco

Phone: 415-353-1206

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place