Timothy D Henry1, Jay H Traverse2, Baron L Hammon2, Cara A East2, Brian Bruckner2, Ann E Remmers2, David Recker2, David A Bull2, Amit N Patel2. 1. From the Division of Cardiology, Cedars-Sinai Medical Center, The Heart Institute, Los Angeles, CA (T.D.H.); Division of Cardiology (T.D.H.) and Cardiovascular Division (J.H.T.), Minneapolis Heart Institute Foundation, MN; Division of Cardiothoracic Surgery (B.L.H.) and Clinical Cardiovascular Research Center (C.A.E.), Soltero Cardiovascular Research Center, Baylor University Medical Center, Dallas, TX; Division of Cardiovascular Surgery, DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (B.B.); Division of Cardiothoracic Surgery, University of Utah School of Medicine, Salt Lake City (D.A.B., A.N.P.); and Aastrom Biosciences, Inc, Ann Arbor, MI (A.E.R., D.R.). henryt@cshs.org. 2. From the Division of Cardiology, Cedars-Sinai Medical Center, The Heart Institute, Los Angeles, CA (T.D.H.); Division of Cardiology (T.D.H.) and Cardiovascular Division (J.H.T.), Minneapolis Heart Institute Foundation, MN; Division of Cardiothoracic Surgery (B.L.H.) and Clinical Cardiovascular Research Center (C.A.E.), Soltero Cardiovascular Research Center, Baylor University Medical Center, Dallas, TX; Division of Cardiovascular Surgery, DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (B.B.); Division of Cardiothoracic Surgery, University of Utah School of Medicine, Salt Lake City (D.A.B., A.N.P.); and Aastrom Biosciences, Inc, Ann Arbor, MI (A.E.R., D.R.).
Abstract
RATIONALE: Ixmyelocel-T is associated with a wide range of biological activities relevant to tissue repair and regeneration. OBJECTIVE: To evaluate the safety and efficacy of ixmyelocel-T in 2 prospective randomized phase 2A Trials administered via minithoracotomy or intramyocardial catheter injections in patients with dilated cardiomyopathy (DCM) stratified by ischemic or nonischemic status. METHODS AND RESULTS: In IMPACT-DCM, patients were randomized to either ixmyelocel-T or standard-of-care control in a 3:1 ratio (n=39); ixmyelocel-T was administered intramyocardially via minithoracotomy. In Catheter-DCM, patients were randomized to either ixmyelocel-T or standard of care control in a 2:1 ratio (n=22); ixmyelocel-T was administered intramyocardially using the NOGA Myostar catheter. Only patients randomized to ixmyelocel-T underwent bone marrow aspiration and injections. In the 2 studies, a total of 61 patients were randomized, and 59 were treated or received standard of care. Fewer ischemic patients treated with ixmyelocel-T experienced a major adverse cardiovascular event during follow-up when compared with control patients. A similar benefit was not seen in the nonischemic patients. Heart failure exacerbation was the most common major adverse cardiovascular event. Ixmyelocel-T treatment was associated with improved New York Heart Association class, 6-minute walk distance, and Minnesota Living with Heart Failure Questionnaire scores in the ischemic population relative to control; a similar trend was not observed in the nonischemic population. CONCLUSIONS:Intramyocardial injection with ixmyelocel-T reduces major adverse cardiovascular event and improves symptoms in patients with ischemic DCM but not in patients with nonischemic DCM.
RCT Entities:
RATIONALE: Ixmyelocel-T is associated with a wide range of biological activities relevant to tissue repair and regeneration. OBJECTIVE: To evaluate the safety and efficacy of ixmyelocel-T in 2 prospective randomized phase 2A Trials administered via minithoracotomy or intramyocardial catheter injections in patients with dilated cardiomyopathy (DCM) stratified by ischemic or nonischemic status. METHODS AND RESULTS: In IMPACT-DCM, patients were randomized to either ixmyelocel-T or standard-of-care control in a 3:1 ratio (n=39); ixmyelocel-T was administered intramyocardially via minithoracotomy. In Catheter-DCM, patients were randomized to either ixmyelocel-T or standard of care control in a 2:1 ratio (n=22); ixmyelocel-T was administered intramyocardially using the NOGA Myostar catheter. Only patients randomized to ixmyelocel-T underwent bone marrow aspiration and injections. In the 2 studies, a total of 61 patients were randomized, and 59 were treated or received standard of care. Fewer ischemicpatients treated with ixmyelocel-T experienced a major adverse cardiovascular event during follow-up when compared with control patients. A similar benefit was not seen in the nonischemic patients. Heart failure exacerbation was the most common major adverse cardiovascular event. Ixmyelocel-T treatment was associated with improved New York Heart Association class, 6-minute walk distance, and Minnesota Living with Heart Failure Questionnaire scores in the ischemic population relative to control; a similar trend was not observed in the nonischemic population. CONCLUSIONS: Intramyocardial injection with ixmyelocel-T reduces major adverse cardiovascular event and improves symptoms in patients with ischemic DCM but not in patients with nonischemic DCM.
Authors: Rienzi Diaz-Navarro; Gerard Urrútia; John Gf Cleland; Daniel Poloni; Francisco Villagran; Roberto Acosta-Dighero; Shrikant I Bangdiwala; Gabriel Rada; Eva Madrid Journal: Cochrane Database Syst Rev Date: 2021-07-21