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NCT02097641: START

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

Completed Phase 2 Results posted Last updated 10 April 2019
What this trial tests

Phase 2 trial testing Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells in Respiratory Distress Syndrome, Adult in 60 participants. Completed in 9 February 2018.

Timeline
15 March 2014
Primary endpoint
9 March 2017
9 February 2018

Quick facts

Lead sponsorMichael A. Matthay
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment60
Start date15 March 2014
Primary completion9 March 2017
Estimated completion9 February 2018
Sites6 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Michael A. Matthay — full company profile →

Who can join

18 and older, any sex, with Respiratory Distress Syndrome, Adult. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Numbers of Patients Occurred Pre-specified Infusion Associated Events Occurring Within 6 Hours of Study Infusion Primary · 6 hours

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-relate

GroupValue95% CI
Human Mesenchymal Stem Cells (hMSCs)0
Plasma-Lyte A (Placebo)0
Numbers of Patients Occurred Any Cardiac Arrest or Death Within 24 Hours of Study Infusion Primary · 24 hours

Within 24 h of study product infusion • Any cardiac arrest or death

GroupValue95% CI
Human Mesenchymal Stem Cells (hMSCs)1
Plasma-Lyte A (Placebo)0
Numbers of Patients Occurred Any Unexpected Severe Adverse Events (Including All-cause Deaths) Primary · 12 months

Safety endpoint: Any unexpected severe adverse events in two groups

GroupValue95% CI
Human Mesenchymal Stem Cells20
Plasma-Lyte A5
PaO2:FiO2 Change From Baseline to Day 3 Secondary · baseline and day 3

Efficacy endpoint: PaO2:FiO2 change from baseline to day 3

GroupValue95% CI
Human Mesenchymal Stem Cells3.7-1.2 – 10.8
Plasma-Lyte A3.5-2.7 – 8.3
Lung Injury Score From Baseline to Day 3 Secondary · baseline and day 3

Murray score for acute lung injury. The range is 0 to 4. The higher score, the worst outcome.

GroupValue95% CI
Human Mesenchymal Stem Cells-0.50-1.00 – -0.25
Plasma-Lyte A-0.33-0.67 – -0.08
Oxygenation Index Change From Baseline to Day 2 Secondary · baseline and day 2

Oxygenation index with the following validated measure of respiratory function: FiO2 (%) x mean airway pressure / PaO2

GroupValue95% CI
Human Mesenchymal Stem Cells-30.3-67.9 – 14.9
Plasma-Lyte A-19.5-47.8 – 10.9
SOFA Score Change From Baseline to Day 3 Secondary · baseline and day 3

Sequential organ failure assessment score (SOFA). The SOFA score ranges from 0 to 24. The higher, the worse.

GroupValue95% CI
Human Mesenchymal Stem Cells-2-4 – 0
Plasma-Lyte A-1-4 – 1
Number of Patients Death to Day 28 Secondary · 28 days

Efficacy endpoint: all-cause mortality at day 28

GroupValue95% CI
Human Mesenchymal Stem Cells12
Plasma-Lyte A3
Mortality to Day 60 Secondary · 60 days

Efficacy endpoint: all-cause mortality at day 60

GroupValue95% CI
Human Mesenchymal Stem Cells15
Plasma-Lyte A5
Number of Ventilator-free Days to Day 28 Secondary · 28 days

Efficacy endpoint: Number of ventilator-free days to day 28.

GroupValue95% CI
Human Mesenchymal Stem Cells20 – 23
Plasma-Lyte A170 – 24
Non-pulmonary Organ-failure-free Days to Day 28 Secondary · 28 days

Efficacy endpoint: Non-pulmonary organ-failure-free days to day 28

GroupValue95% CI
Human Mesenchymal Stem Cells124 – 24
Plasma-Lyte A84 – 15
Angiopoietin 2 Change From Baseline to 6 h Secondary · baseline and 6 hours

Biological markers of endothelial injury: angiopoietin 2

GroupValue95% CI
Human Mesenchymal Stem Cells-1120-4706 – -66
Plasma-Lyte A287-1005 – 2374

Adverse events — posted to ClinicalTrials.gov

Time frame: 60 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Human Mesenchymal Stem Cells
Serious: 17/40 (43%)
Deaths: 15/40
Plasma-Lyte A
Serious: 11/20 (55%)
Deaths: 5/20

Serious adverse events (21 terms)

ReactionSystemHuman Mesenchymal Stem CellsPlasma-Lyte A
Death due to multi-organ failureGeneral disorders
Death due to worsening respiratory failureRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Lower extremity weaknessNervous system disorders
Hospital readmission due to post-surgical painSurgical and medical procedures
Acute renal failureRenal and urinary disorders
Hospital readmission due to pyelonephritisRenal and urinary disorders
Acute leukemiaBlood and lymphatic system disorders
Diffuse alveolar hemorrhageBlood and lymphatic system disorders
Death due to cardiac arrestCardiac disorders
Myocardial ischemiaCardiac disorders
BradycardiaCardiac disorders
TachycardiaCardiac disorders
Pericardial effusionCardiac disorders
Heart blockCardiac disorders
Ischemic strokeCardiac disorders
Liver abscessHepatobiliary disorders
Acute pancreatitisHepatobiliary disorders
Worsening respiratory failure, recoveredRespiratory, thoracic and mediastinal disorders
Aspiration pneumonitisRespiratory, thoracic and mediastinal disorders
Calvarial bone marrow abnormalityBlood and lymphatic system disorders
Other adverse events (4 terms — click to expand)

ReactionSystemHuman Mesenchymal Stem CellsPlasma-Lyte A
HepatitisHepatobiliary disorders
Fecal and urinary incontinenceRenal and urinary disorders
Deep venous thrombosisVascular disorders
Acute anemiaBlood and lymphatic system disorders

Most-reported serious reactions: Death due to multi-organ failure, Death due to worsening respiratory failure, Pulmonary embolism, Lower extremity weakness, Hospital readmission due to post-surgical pain, Acute renal failure, Hospital readmission due to pyelonephritis, Acute leukemia.

Data from ClinicalTrials.gov NCT02097641 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Challenges and advances in clinical applications of mesenchymal stromal cells.
    Zhou T, Yuan Z, Weng J, Pei D, et al · · 2021 · cited 489× · PMID 33579329 · DOI 10.1186/s13045-021-01037-x
  2. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial.
    Matthay MA, Calfee CS, Zhuo H, Thompson BT, et al · · 2019 · cited 465× · PMID 30455077 · DOI 10.1016/s2213-2600(18)30418-1
  3. A Brief Overview of Global Trends in MSC-Based Cell Therapy.
    Jovic D, Yu Y, Wang D, Wang K, et al · · 2022 · cited 186× · PMID 35344199 · DOI 10.1007/s12015-022-10369-1
  4. Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe <i>E. coli</i> pneumonia.
    Park J, Kim S, Lim H, Liu A, et al · · 2019 · cited 158× · PMID 30076187 · DOI 10.1136/thoraxjnl-2018-211576
  5. Mesenchymal Stem Cell-Based Therapy of Inflammatory Lung Diseases: Current Understanding and Future Perspectives.
    Harrell CR, Sadikot R, Pascual J, Fellabaum C, et al · · 2019 · cited 144× · PMID 31191672 · DOI 10.1155/2019/4236973
  6. Sepsis and Acute Respiratory Distress Syndrome: Recent Update.
    Kim WY, Hong SB. · · 2016 · cited 136× · PMID 27066082 · DOI 10.4046/trd.2016.79.2.53
  7. Pharmacological agents for adults with acute respiratory distress syndrome.
    Lewis SR, Pritchard MW, Thomas CM, Smith AF. · · 2019 · cited 128× · PMID 31334568 · DOI 10.1002/14651858.cd004477.pub3
  8. Targeted Therapy for Inflammatory Diseases with Mesenchymal Stem Cells and Their Derived Exosomes: From Basic to Clinics.
    Wang S, Lei B, Zhang E, Gong P, et al · · 2022 · cited 125× · PMID 35469174 · DOI 10.2147/ijn.s355366

Verify or expand the search:

Other recruiting trials for Respiratory Distress Syndrome, Adult

Currently open trials in the same condition.

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