Comparison of Allogeneic vs Autologous Bone Marrow-Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy - POSEIDON

Description:

The goal of the trial was to evaluate transendocardial injection of allogeneic mesenchymal stem cells compared with autologous mesenchymal stem cells among patients with ischemic cardiomyopathy.

Hypothesis:

The goal of this study was to demonstrate the safety of allogeneic mesenchymal stem cells.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Patients 21-90 years of age with left ventricular dysfunction due to prior myocardial infarction
  • Left ventricular ejection fraction <50%
  • Eligibility for cardiac catheterization

    Number of screened applicants: 96
    Number of enrollees: 31
    Duration of follow-up: 12 months
    Mean patient age: 63 years
    Percentage female: 13%
    Ejection fraction: 27%
    NYHA class: I-13%, II-60%, III-27%

Exclusions:

  • Limited life expectancy
  • Renal insufficiency
  • Serious contrast allergy
  • Need for coronary revascularization
  • Life-threatening arrhythmia without an implanted defibrillator
  • Malignancy within the last 5 years

Primary Endpoints:

  • Safety of transendocardial injection of allogeneic mesenchymal stem cells (treatment emergent serious adverse event)

Secondary Endpoints:

  • Long-term safety of allogeneic mesenchymal stem cells
  • Long-term efficacy of allogeneic mesenchymal stem cells

Drug/Procedures Used:

Patients with ischemic cardiomyopathy were randomized in this phase I/II study to transendocardial injection of allogeneic mesenchymal stem cells (n = 15) versus autologous mesenchymal stem cells (n = 16).

Allogeneic mesenchymal stem cells were prepared from bone marrow aspirates of healthy donors. Patients in the autologous mesenchymal stem cells group underwent bone marrow aspiration 4 to 6 weeks before cardiac catheterization, at which time they were prepared in culture.

One-third of the patients received 20 million mesenchymal stem cells, one-third received 100 million mesenchymal stem cells, and one-third received 200 million mesenchymal stem cells.

Transendocardial injection was performed to 10 sites in the infarcted myocardium with the Biocardia Helical Infusion catheter.

Principal Findings:

Overall, 31 patients were randomized. The mean age was 63 years, 13% were women, mean ejection fraction was 27%, 73% of patients had an implanted defibrillator, 27% had diabetes, and the mean distance achieved on the 6-minute walk test was 391 m.

Serious adverse events at 30 days occurred in one patient in the allogeneic group versus three patients in the autologous group. Adverse events occurred in six patients in the allogeneic group versus 17 patients in the autologous group. Serious adverse events at 1 year occurred in 33% versus 53% (p = 0.46), respectively.

There were no deaths in either group. Rehospitalization at 12 months occurred 33% of the allogeneic group versus 40% of the autologous group (p > 0.99). Rehospitalization for worsening heart failure at 12 months occurred 13% of the allogeneic group versus 27% of the autologous group (p = 0.65).

Interpretation:

Among patients with ischemic cardiomyopathy, transendocardial injection of allogeneic mesenchymal stem cells met the prespecified criteria for safety compared with autologous mesenchymal stem cells. Transendocardial injection of mesenchymal stem cells warrants further study.

References:

Hare JM, Fishman JE, Gerstenblith G, et al. Comparison of Allogeneic vs Autologous Bone Marrow-Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy: The POSEIDON Randomized Trial. JAMA 2012;308:2369-79.

Presented by Dr. Joshua Hare at the American Heart Association Scientific Sessions, Los Angeles, CA, November 6, 2012.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Implantable Devices, SCD/Ventricular Arrhythmias, Acute Heart Failure

Keywords: Myocardial Infarction, Follow-Up Studies, Bone Marrow, Mesenchymal Stromal Cells, Cardiomyopathies, Cardiac Catheterization, Heart Failure, Ventricular Dysfunction, Left, Defibrillators, Implantable, Diabetes Mellitus


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