Randomized Comparison of Allogeneic Vs. Autologous Mesenchymal Stem Cells for Non-lschemic Dilated Cardiomyopathy: POSEIDON-DCM Trial

Abstract Background While human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic non-ischemic dilated cardiomyopathy (NIDCM). Objectives The POSEIDON-DCM trial is a randomized comparison of safety and efficacy of autologous (auto) vs. allogenei...

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Veröffentlicht in:	Journal of the American College of Cardiology 2016-11, Vol.69 (5), p.526-537
Hauptverfasser:	Hare, Joshua M., MD, DiFede, Darcy L., RN BSN, Castellanos, Angela M., MD MSc, Florea, Victoria, MD, Landin, Ana M., PhD, El-Khorazaty, Jill, MSc, Khan, Aisha, MSc MBA, Mushtaq, Muzammil, MD, Lowery, Maureen H., MD, Byrnes, John J., MD, Hendel, Robert C., MD, Cohen, Mauricio G., MD, Alfonso, Carlos E., MD, Valasaki, Krystalenia, MSc, Pujol, Marietsy V., MDA, Golpanian, Samuel, MD, Ghersin, Eduard, MD, Fishman, Joel E., MD PhD, Pattany, Pradip, PhD, Gomes, Samirah A., MD PhD, Delgado, Cindy, MFA, Miki, Roberto, MD, Abuzeid, Fouad, MD, Vidro-Casiano, Mayra, MPH, Premer, Courtney, BSc, Medina, Audrey, BSc, Porras, Valeria, BSc, Hatzistergos, Konstantinos E., PhD, Anderson, Erica, MSc, Mendizabal, Adam, PhD, Mitrani, Raul, MD, Heldman, Alan W., MD
Format:	Artikel
Sprache:	eng
Schlagworte:	Cardiovascular Internal Medicine
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Zusammenfassung:	Abstract Background While human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic non-ischemic dilated cardiomyopathy (NIDCM). Objectives The POSEIDON-DCM trial is a randomized comparison of safety and efficacy of autologous (auto) vs. allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients (age: 55.8 + 11.2; 32% female) received hMSCs (100 million) by transendocardial stem cell injection (TESI) in ten left ventricular sites by NOGA Catheter. Treated patients were evaluated at baseline, 30 days, 3-, 6-, and 12-months for safety: serious adverse events (SAE), and efficacy endpoints: Ejection Fraction (EF), Minnesota Living with Heart Failure Questionnaire (MLHFQ), Six Minute Walk Test (6MWT), MACE, and immune-biomarkers. This trial is registered with ClinicalTrials.gov , #NCT01392625. Results There were no 30-day treatment-emergent (TE)-SAEs. 12-month SAE incidence was 28.2% (95% CI: 12.8, 55.1) in allo, and 63.5% (95% CI: 40.8, 85.7; p=0.1004) in auto. One allo-group patient developed an elevated donor specific cPRA. EF increased in allo by 8.0 units (95% Cl: 2.8, 13.2; p=0.004), and in auto: 5.4 units (95% Cl: -1.4, 12.1; p=0.116, allo vs. auto p=0.4887). 6MWT increased for allo: 37.0 meters (95% Cl: 2.0 to 72.0; p=0.04), but not auto: 7.3 meters (95% Cl: -47.8, 33.3; p=0.71, auto vs. allo p=0.0168). MLHFQ score decreased in allo (p=0.0022), and auto (p=0.463; p=0.172). The MACE rate was lower in allo vs. auto (p=0.0186). Tumor necrosis factor alpha (TNF-α) decreased (p=0.0001 for each), to a greater extent in allo vs. auto at six-months (p=0.05). Conclusion These findings demonstrate safety and support greater, clinically meaningful efficacy of allo-hMSC vs. auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results.
ISSN:	0735-1097 1558-3597
DOI:	10.1016/j.jacc.2016.11.009