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Randomized Controlled Trial
. 2014 Jun 3;129(22):2287-96.
doi: 10.1161/CIRCULATIONAHA.113.007412. Epub 2014 Mar 28.

Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices

Deborah D Ascheim  1 , Annetine C Gelijns  2 , Daniel Goldstein  2 , Lemuel A Moye  2 , Nicholas Smedira  2 , Sangjin Lee  2 , Charles T Klodell  2 , Anita Szady  2 , Michael K Parides  2 , Neal O Jeffries  2 , Donna Skerrett  2 , Doris A Taylor  2 , J Eduardo Rame  2 , Carmelo Milano  2 , Joseph G Rogers  2 , Janine Lynch  2 , Todd Dewey  2 , Eric Eichhorn  2 , Benjamin Sun  2 , David Feldman  2 , Robert Simari  2 , Patrick T O'Gara  2 , Wendy C Taddei-Peters  2 , Marissa A Miller  2 , Yoshifumi Naka  2 , Emilia Bagiella  2 , Eric A Rose  2 , Y Joseph Woo  2
Affiliations
Randomized Controlled Trial

Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices

Deborah D Ascheim et al. Circulation. .

Abstract

Background: Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy.

Methods and results: In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (P=0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months.

Conclusions: In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT01442129.

Keywords: heart failure; left ventricular assist device; randomized controlled trial; stem cell.

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Conflict of interest statement

Conflict of Interest Disclosures: Authors report the following: D.D. Ascheim, none; E. Bagiella, none; T. Dewey, none; E. Eichhorn, none; D. Feldman, Thoratec Inc., HeartWare, Inc. consultant; A.C. Gelijns, none; D. Goldstein, Medical advisory board, Thoratec Inc.; Consultant, Heartware Inc.; N. Jeffries, none; C.T. Klodell, none; S. Lee, none; J. Lynch, none; C. Milano, Thoratec Inc., HeartWare Inc. consultant; M.A. Miller, none; Y. Naka, Thoratec Inc. consultant; P.T. O’Gara, none; J.E. Rame, Thoratec, Inc., Heartware Inc. research funding; J.G. Rogers, Thoratec consultant; E.A. Rose, Board of Directors, Mesoblast, Inc.; R. Simari, none; N. Smedira, none; L.A. Moye, none; M.K. Parides, none; D. Skerrett, Chief Medical Officer, Mesoblast, Inc.; B. Sun, Thoratec Inc., Sunshine Heart consultant; A. Szady, none; W. Taddei-Peters, none; D.A. Taylor, Miromatrix Medical Inc, founder; Y.J. Woo, none

Figures

Figure 1
Figure 1
CONSORT Diagram.
Figure 2
Figure 2
Survival. Crosses depict censored patients.
Figure 3
Figure 3
Posterior Distribution Analysis Curve. Difference = Difference in response-rates (MPC-Placebo); 93% of the area under the curve is between 0–1, corresponding to the probability that MPCs provide better response than placebo.
Figure 4
Figure 4
Duration of LVAD Wean.
Figure 5
Figure 5
Number of Successful Weans.
See this image and copyright information in PMC

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