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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02097641
Recruitment Status : Completed
First Posted : March 27, 2014
Results First Posted : April 10, 2019
Last Update Posted : April 10, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Massachusetts General Hospital
Stanford University
University of Pittsburgh
University of Minnesota
Ohio State University
Information provided by (Responsible Party):
Michael A. Matthay, University of California, San Francisco

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Respiratory Distress Syndrome, Adult
Interventions Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells
Biological: Plasma-Lyte A
Enrollment 60
Recruitment Details From March 24, 2014, to Feb 9, 2017, 1038 patients were screened for eligibility, of whom 975 were excluded, and 63 were randomly assigned to a treatment group. Three patients were not eligible for treatment after randomization and, therefore, 40 patients received human mesenchymal stem cells and 20 patients received placebo.
Pre-assignment Details Three patients who were randomly assigned to receive human mesenchymal stem cells, were excluded: 2 did not meet baseline stability criteria; 1 patient's PaO2:FiO2 > 200 mmHg.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Period Title: Overall Study
Started 40 20
Completed 40 20
Not Completed 0 0
Arm/Group Title Human Mesenchymal Stem Cells (hMSCs) Plasma-Lyte A (Placebo) Total
Hide Arm/Group Description

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Total of all reporting groups
Overall Number of Baseline Participants 40 20 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 20 participants 60 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
30
  75.0%
12
  60.0%
42
  70.0%
>=65 years
10
  25.0%
8
  40.0%
18
  30.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants 20 participants 60 participants
55  (17) 55  (20) 55  (18)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 20 participants 60 participants
Female
23
  57.5%
10
  50.0%
33
  55.0%
Male
17
  42.5%
10
  50.0%
27
  45.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 20 participants 60 participants
Hispanic or Latino
4
  10.0%
2
  10.0%
6
  10.0%
Not Hispanic or Latino
31
  77.5%
16
  80.0%
47
  78.3%
Unknown or Not Reported
5
  12.5%
2
  10.0%
7
  11.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 20 participants 60 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   5.0%
2
  10.0%
4
   6.7%
Native Hawaiian or Other Pacific Islander
3
   7.5%
0
   0.0%
3
   5.0%
Black or African American
4
  10.0%
1
   5.0%
5
   8.3%
White
27
  67.5%
13
  65.0%
40
  66.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
  10.0%
4
  20.0%
8
  13.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 40 participants 20 participants 60 participants
40 20 60
Cause of Acute Respiratory Distress Syndrome (ARDS)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 20 participants 60 participants
Sepsis with pneumonia
19
  47.5%
12
  60.0%
31
  51.7%
Sepsis without pneumonia
5
  12.5%
2
  10.0%
7
  11.7%
Pneumonia without sepsis
11
  27.5%
5
  25.0%
16
  26.7%
Aspiration only
4
  10.0%
1
   5.0%
5
   8.3%
Other
1
   2.5%
0
   0.0%
1
   1.7%
Arterial pressure  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 40 participants 20 participants 60 participants
75  (10) 76  (9) 75  (10)
Taking vasopressors at the time of infusion  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 20 participants 60 participants
24
  60.0%
9
  45.0%
33
  55.0%
Sequential Organ Failure Assessment (SOFA)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 40 participants 19 participants 59 participants
8.1  (3.3) 6.9  (2.7) 7.7  (3.2)
[1]
Measure Description: SOFA score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems which are added up. Each score ranges from 0 to 4. SOFA score ranges from 0 (best) to 24 (worst).
[2]
Measure Analysis Population Description: Data not recorded in one patient treated with Plasma-Lyte A (placebo).
Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) III score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 40 participants 19 participants 59 participants
104  (31) 89  (33) 99  (32)
[1]
Measure Description: The range of APACHE III is from 0 to 299. The higher score, the worse clinical outcome.
[2]
Measure Analysis Population Description: Data not recorded in one patient treated with Plasma-Lyte (placebo).
Minute ventilation  
Mean (Standard Deviation)
Unit of measure:  L/min
Number Analyzed 40 participants 20 participants 60 participants
11.1  (3.2) 9.6  (2.4) 10.6  (3.0)
Respiratory rate  
Mean (Standard Deviation)
Unit of measure:  Breaths/min
Number Analyzed 40 participants 20 participants 60 participants
27.8  (6.6) 24.5  (6.3) 26.7  (6.6)
Tidal volume   [1] 
Mean (Standard Deviation)
Unit of measure:  mL/kg predicted body weight
Number Analyzed 39 participants 20 participants 59 participants
6.3  (0.9) 6.1  (0.7) 6.2  (0.9)
[1]
Measure Analysis Population Description: Data not recorded in one patient treated with hMSCs.
Mean airway pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm H2O
Number Analyzed 37 participants 19 participants 56 participants
17.8  (4.9) 16.4  (3.6) 17.4  (4.6)
[1]
Measure Analysis Population Description: Data not recorded in three patients treated with hMSCs and one patient treated with Plasma-Lyte A (placebo).
Plateau airway pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm H2O
Number Analyzed 30 participants 15 participants 45 participants
26.4  (5.7) 23.7  (5.1) 25.5  (5.6)
[1]
Measure Analysis Population Description: 15 patients did not have baseline plateau pressure recorded.
Positive end-expiratory pressure (PEEP)  
Mean (Standard Deviation)
Unit of measure:  Cm H2O
Number Analyzed 40 participants 20 participants 60 participants
12.4  (3.7) 10.8  (2.6) 11.8  (3.4)
Driving pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm H2O
Number Analyzed 30 participants 15 participants 45 participants
14.0  (4.1) 12.5  (4.3) 13.5  (4.2)
[1]
Measure Analysis Population Description: Data not recorded in 10 patients treated with hMSCs and in 5 patients treated with Plasma-Lyte (placebo).
PaO2/FiO2  
Mean (Standard Deviation)
Unit of measure:  kPa
Number Analyzed 40 participants 20 participants 60 participants
18.1  (4.3) 19.1  (5.2) 18.4  (4.6)
Oxygenation index   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  kPa
Number Analyzed 37 participants 19 participants 56 participants
108.1  (45.9) 95.7  (41.2) 103.9  (44.4)
[1]
Measure Description: Oxygenation index calculated as: FiO2 (%) x Mean Airway Pressure / PaO2
[2]
Measure Analysis Population Description: Data not recorded in 3 patients treated with hMSCs and 1 patient treated with Plasma-Lyte (placebo).
Lung injury score (LIS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 40 participants 20 participants 60 participants
3.1  (0.4) 3.0  (0.5) 3.1  (0.4)
[1]
Measure Description: LIS is a composite 4-point scoring system including the PaO2/FiO2, PEEP, lung compliance, and the extent of infiltrates on the chest X-ray. Each of the four components is categorized from 0 to 4, where a higher number is worse. The total Lung Injury Score is obtained by dividing the aggregate sum by the number of components used.
Ventilation mode  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 20 participants 60 participants
Volume control
37
  92.5%
17
  85.0%
54
  90.0%
Pressure-regulated volume control
1
   2.5%
2
  10.0%
3
   5.0%
Other
2
   5.0%
1
   5.0%
3
   5.0%
1.Primary Outcome
Title Numbers of Patients Occurred Pre-specified Infusion Associated Events Occurring Within 6 Hours of Study Infusion
Hide Description

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)
Time Frame 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Human Mesenchymal Stem Cells (hMSCs) Plasma-Lyte A (Placebo)
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 40 20
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Numbers of Patients Occurred Any Cardiac Arrest or Death Within 24 Hours of Study Infusion
Hide Description

Within 24 h of study product infusion

• Any cardiac arrest or death

Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Human Mesenchymal Stem Cells (hMSCs) Plasma-Lyte A (Placebo)
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 40 20
Measure Type: Count of Participants
Unit of Measure: Participants
1
   2.5%
0
   0.0%
3.Primary Outcome
Title Numbers of Patients Occurred Any Unexpected Severe Adverse Events (Including All-cause Deaths)
Hide Description Safety endpoint: Any unexpected severe adverse events in two groups
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 40 20
Measure Type: Count of Participants
Unit of Measure: Participants
20
  50.0%
5
  25.0%
4.Secondary Outcome
Title PaO2:FiO2 Change From Baseline to Day 3
Hide Description Efficacy endpoint: PaO2:FiO2 change from baseline to day 3
Time Frame baseline and day 3
Hide Outcome Measure Data
Hide Analysis Population Description
The values of PaO2:FiO2 were not available in 10 patients treated with hMSCs and in 2 patients treated with placebo.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 30 18
Median (Inter-Quartile Range)
Unit of Measure: kPa
3.7
(-1.2 to 10.8)
3.5
(-2.7 to 8.3)
5.Secondary Outcome
Title Lung Injury Score From Baseline to Day 3
Hide Description Murray score for acute lung injury. The range is 0 to 4. The higher score, the worst outcome.
Time Frame baseline and day 3
Hide Outcome Measure Data
Hide Analysis Population Description
The values were missing in 9 hMSC patients and 2 placebo patients.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 31 18
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
-0.50
(-1.00 to -0.25)
-0.33
(-0.67 to -0.08)
6.Secondary Outcome
Title Oxygenation Index Change From Baseline to Day 2
Hide Description Oxygenation index with the following validated measure of respiratory function: FiO2 (%) x mean airway pressure / PaO2
Time Frame baseline and day 2
Hide Outcome Measure Data
Hide Analysis Population Description
The values were missing in 16 patients treated by MSC and 6 patients treated by placebo
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 24 14
Median (Inter-Quartile Range)
Unit of Measure: kPa
-30.3
(-67.9 to 14.9)
-19.5
(-47.8 to 10.9)
7.Secondary Outcome
Title SOFA Score Change From Baseline to Day 3
Hide Description Sequential organ failure assessment score (SOFA). The SOFA score ranges from 0 to 24. The higher, the worse.
Time Frame baseline and day 3
Hide Outcome Measure Data
Hide Analysis Population Description
The values were missing in 3 MSC patients and 1 placebo patient.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 37 19
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
-2
(-4 to 0)
-1
(-4 to 1)
8.Secondary Outcome
Title Number of Patients Death to Day 28
Hide Description Efficacy endpoint: all-cause mortality at day 28
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 40 20
Measure Type: Count of Participants
Unit of Measure: Participants
12
  30.0%
3
  15.0%
9.Secondary Outcome
Title Mortality to Day 60
Hide Description Efficacy endpoint: all-cause mortality at day 60
Time Frame 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 40 20
Measure Type: Count of Participants
Unit of Measure: Participants
15
  37.5%
5
  25.0%
10.Secondary Outcome
Title Number of Ventilator-free Days to Day 28
Hide Description Efficacy endpoint: Number of ventilator-free days to day 28.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 40 20
Median (Inter-Quartile Range)
Unit of Measure: days
2
(0 to 23)
17
(0 to 24)
11.Secondary Outcome
Title Non-pulmonary Organ-failure-free Days to Day 28
Hide Description Efficacy endpoint: Non-pulmonary organ-failure-free days to day 28
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 40 20
Median (Inter-Quartile Range)
Unit of Measure: days
12
(4 to 24)
8
(4 to 15)
12.Secondary Outcome
Title Angiopoietin 2 Change From Baseline to 6 h
Hide Description Biological markers of endothelial injury: angiopoietin 2
Time Frame baseline and 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The biomarker values were missing in one patient treated with hMSC and one patient treated with placebo.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 39 19
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
-1120
(-4706 to -66)
287
(-1005 to 2374)
13.Secondary Outcome
Title Angiopoietin 2 Change From Baseline to 24 h
Hide Description Biological markers of endothelial injury: angiopoietin 2
Time Frame baseline and 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The values were not available in two patients treated with hMSC and two patients treated with placebo.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 38 18
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
-2080
(-6404 to 47)
-537
(-4294 to 1029)
14.Secondary Outcome
Title Interleukin 6 Change From Baseline to 6 h
Hide Description Biological markers of inflammation: interleukin 6
Time Frame baseline and 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The values were not available in one patient treated with hMSC and one patient treated with placebo.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 39 19
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
-51
(-124 to 4)
-20
(-71 to 17)
15.Secondary Outcome
Title Interleukin 6 Change From Baseline to 24 h
Hide Description Biological markers of inflammation: interleukin 6
Time Frame baseline and 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The values were not available in two patients treated with hMSC and two patients treated with placebo.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 38 18
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
-34
(-137 to 4)
-43
(-165 to 39)
16.Secondary Outcome
Title Interleukin 8 Change From Baseline to 6 h
Hide Description Biological markers of inflammation: interleukin 8
Time Frame baseline and 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The values were not available in one patient treated with hMSC and one patient treated with placebo.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 39 19
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
-2
(-24 to 3)
-1
(-8 to 1)
17.Secondary Outcome
Title Interleukin 8 Change From Baseline to 24 h
Hide Description Biological markers of inflammation: interleukin 8
Time Frame baseline and 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The values were not available in two patients treated with hMSC and two patients treated with placebo.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 38 18
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
-5
(-34 to 4)
-5
(-17 to -1)
18.Secondary Outcome
Title RAGE Change From Baseline to 6 h
Hide Description Biological markers of alveolar epithelial injury: receptor for advanced glycation end products (RAGE)
Time Frame baseline and 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The values were not available in one patient treated with hMSC and one patient treated with placebo.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 39 19
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
-326
(-888 to -45)
-322
(-624 to -93)
19.Secondary Outcome
Title RAGE Change From Baseline to 24 h
Hide Description Biological markers of alveolar epithelial injury: receptor for advanced glycation end products (RAGE)
Time Frame baseline and 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The values were not available in two patients treated with hMSC and two patients treated with placebo.
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description:

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

Overall Number of Participants Analyzed 38 18
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
-393
(-1118 to -78)
-411
(-1057 to -110)
Time Frame 60 days
Adverse Event Reporting Description
  1. All-cause mortality by day 60 after study product infusion
  2. Serious adverse events, expected and unexpected, also included any deaths through study day 28 (none of them were related to study product or study procedures per DSMB review)
  3. Please see our Lancet Resp Medicine 2018 publication (citation included) for further details including adjusted analyses of baseline differences between the MSC and placebo treated groups
 
Arm/Group Title Human Mesenchymal Stem Cells Plasma-Lyte A
Hide Arm/Group Description

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

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously over approximately 60-80 minutes.

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

Plasma-Lyte A: Plasma-Lyte A placebo will be administered intravenously over approximately 60-80 minutes.

All-Cause Mortality
Human Mesenchymal Stem Cells Plasma-Lyte A
Affected / at Risk (%) Affected / at Risk (%)
Total   15/40 (37.50%)      5/20 (25.00%)    
Hide Serious Adverse Events
Human Mesenchymal Stem Cells Plasma-Lyte A
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/40 (42.50%)      11/20 (55.00%)    
Blood and lymphatic system disorders     
Acute leukemia *  0/40 (0.00%)  0 1/20 (5.00%)  1
Diffuse alveolar hemorrhage *  1/40 (2.50%)  1 0/20 (0.00%)  0
Calvarial bone marrow abnormality *  1/40 (2.50%)  1 0/20 (0.00%)  0
Cardiac disorders     
Death due to cardiac arrest *  1/40 (2.50%)  1 1/20 (5.00%)  1
Myocardial ischemia *  1/40 (2.50%)  1 0/20 (0.00%)  0
Bradycardia *  1/40 (2.50%)  1 0/20 (0.00%)  0
Tachycardia *  1/40 (2.50%)  1 0/20 (0.00%)  0
Pericardial effusion *  1/40 (2.50%)  1 0/20 (0.00%)  0
Heart block *  1/40 (2.50%)  1 0/20 (0.00%)  0
Ischemic stroke *  0/40 (0.00%)  0 1/20 (5.00%)  1
General disorders     
Death due to multi-organ failure *  8/40 (20.00%)  8 2/20 (10.00%)  2
Hepatobiliary disorders     
Liver abscess *  0/40 (0.00%)  0 1/20 (5.00%)  1
Acute pancreatitis *  0/40 (0.00%)  0 1/20 (5.00%)  1
Nervous system disorders     
Lower extremity weakness *  0/40 (0.00%)  0 1/20 (5.00%)  1
Renal and urinary disorders     
Acute renal failure *  1/40 (2.50%)  1 0/20 (0.00%)  0
Hospital readmission due to pyelonephritis *  0/40 (0.00%)  0 1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders     
Death due to worsening respiratory failure *  3/40 (7.50%)  3 0/20 (0.00%)  0
Worsening respiratory failure, recovered *  0/40 (0.00%)  0 1/20 (5.00%)  1
Aspiration pneumonitis *  1/40 (2.50%)  1 0/20 (0.00%)  0
Pulmonary embolism *  1/40 (2.50%)  1 2/20 (10.00%)  2
Surgical and medical procedures     
Hospital readmission due to post-surgical pain *  0/40 (0.00%)  0 1/20 (5.00%)  1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Human Mesenchymal Stem Cells Plasma-Lyte A
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/40 (5.00%)      2/20 (10.00%)    
Blood and lymphatic system disorders     
Acute anemia *  0/40 (0.00%)  1/20 (5.00%) 
Hepatobiliary disorders     
Hepatitis *  1/40 (2.50%)  0/20 (0.00%) 
Renal and urinary disorders     
Fecal and urinary incontinence *  0/40 (0.00%)  1/20 (5.00%) 
Vascular disorders     
Deep venous thrombosis *  1/40 (2.50%)  0/20 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Michael A. Matthay, MD
Organization: University of California San Francisco
Phone: 415-502-7434
EMail: michael.matthay@ucsf.edu
Layout table for additonal information
Responsible Party: Michael A. Matthay, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02097641    
Other Study ID Numbers: UCSF-hMSC-ARDS-P2
1U01HL108713-01 ( U.S. NIH Grant/Contract )
First Submitted: March 19, 2014
First Posted: March 27, 2014
Results First Submitted: January 15, 2019
Results First Posted: April 10, 2019
Last Update Posted: April 10, 2019