A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor Cells in Patients With Ischemic or Nonischemic Heart Failure. Issue 6 (28th August 2015)

• Record Type: Journal Article
• Authors: Perin, Emerson C.; Borow, Kenneth M.; Silva, Guilherme V.; DeMaria, Anthony N.; Marroquin, Oscar C.; Huang, Paul P.; Traverse, Jay H.; Krum, Henry; Skerrett, Donna; Zheng, Yi; Willerson, James T.; Itescu, Silviu; Henry, Timothy D.
• Is Part Of: Circulation research. Volume 117:Issue 6(2015)
• Publication Date: 2015-08-28
• Subjects: Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.115.306332
• Languages: English
• ISSNs: 0009-7330

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title> <underline>Rationale:</underline> </title> <p>Allogeneic mesenchymal precursor cells (MPCs) have been effective in large animal models of ischemic and nonischemic heart failure (HF).</p> </sec> <sec> <title> <underline>Objective:</underline> </title> <p>To evaluate the feasibility and safety of 3 doses (25, 75, or 150 million cells) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial.</p> </sec> <sec> <title> <underline>Methods and Results:</underline> </title> <p>We sequentially allocated 60 patients to a dosing cohort (20 per dose group) and randomized them to transendocardial MPC injections (n=15) or mock procedures (n=5). The primary objective was safety, including antibody testing. Secondary efficacy end points included major adverse cardiac events (MACE; cardiac death, myocardial infarction, or revascularization), left ventricular imaging, and other clinical-event surrogates. Safety and MACE were evaluated for up to 3 years. MPC injections were feasible and safe. Adverse events were similar across groups. No clinically symptomatic immune responses were noted. MACE was seen in 15 patients: 10 of 45 (22%) MPC-treated and 5 of 15 (33%) control patients. We found no differences between MPC-treated and control patients in survival probability, MACE-free probability, and all-cause mortality. We conducted a post hoc analysis of HF-related MACE (HF hospitalization, successfully resuscitated cardiac death, or cardiac death) and events were significantly reduced in the 150 million MPC group (0/15) versus control (5/15; 33%), 25 million MPC group (3/15; 20%), and 75 million MPC group (6/15; 40%); the 150 million MPC group differed significantly from all groups according to Kaplan–Meier statistics >3 years (<italic>P</italic>=0.025 for 150 million MPC group versus control).</p> </sec> <sec> <title> <underline>Conclusions:</underline> </title> <p>Transendocardial injections of allogeneic MPCs were feasible and safe in chronic HF patients. High-dose allogeneic MPCs may provide benefits in this population.</p> </sec> </abstract>