Norbert Frey1, Axel Linke1, Tim Süselbeck1, Jochen Müller-Ehmsen1, Paul Vermeersch1, Danny Schoors1, Mark Rosenberg1, Florian Bea1, Shmuel Tuvia1, Jonathan Leor2. 1. From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.). 2. From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.). leorj@post.tau.ac.il.
Abstract
BACKGROUND: We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative, injectable bioabsorbable scaffold (IK-5001), to prevent or reverse adverse left ventricular remodeling and dysfunction in patients after ST-segment-elevation myocardial infarction. METHODS AND RESULTS: Patients (n=27) with moderate-to-large ST-segment-elevation myocardial infarctions, after successful revascularization, were enrolled. Two milliliters of IK-5001, a solution of 1% sodium alginate plus 0.3% calcium gluconate, was administered by selective injection through the infarct-related coronary artery within 7 days after myocardial infarction. IK-5001 is assumed to permeate the infarcted tissue, cross-linking into a hydrogel and forming a bioabsorbable cardiac scaffold. Coronary angiography, 3 minutes after injection, confirmed that the injection did not impair coronary flow and myocardial perfusion. Furthermore, IK-5001 deployment was not associated with additional myocardial injury or re-elevation of cardiac biomarkers. Clinical assessments, echocardiographic studies, 12-lead electrocardiograms, 24-hour Holter monitoring, blood tests, and completion of Minnesota Living with Heart Failure Questionnaires were repeated during follow-up visits at 30, 90, and 180 days after treatment. During a 6-month follow-up, these tests confirmed favorable tolerability of the procedure, without device-related adverse events, serious arrhythmias, blood test abnormalities, or death. Serial echocardiographic studies showed preservation of left ventricular indices and left ventricular ejection fraction. CONCLUSIONS: This first-in-man pilot study shows that intracoronary deployment of an IK-5001 scaffold is feasible and well tolerated. Our results have promoted the initiation of a multicenter, randomized controlled trial to confirm the safety and efficacy of this new approach in high-risk patients after ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01226563.
RCT Entities:
BACKGROUND: We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative, injectable bioabsorbable scaffold (IK-5001), to prevent or reverse adverse left ventricular remodeling and dysfunction in patients after ST-segment-elevation myocardial infarction. METHODS AND RESULTS:Patients (n=27) with moderate-to-large ST-segment-elevation myocardial infarctions, after successful revascularization, were enrolled. Two milliliters of IK-5001, a solution of 1% sodium alginate plus 0.3% calcium gluconate, was administered by selective injection through the infarct-related coronary artery within 7 days after myocardial infarction. IK-5001 is assumed to permeate the infarcted tissue, cross-linking into a hydrogel and forming a bioabsorbable cardiac scaffold. Coronary angiography, 3 minutes after injection, confirmed that the injection did not impair coronary flow and myocardial perfusion. Furthermore, IK-5001 deployment was not associated with additional myocardial injury or re-elevation of cardiac biomarkers. Clinical assessments, echocardiographic studies, 12-lead electrocardiograms, 24-hour Holter monitoring, blood tests, and completion of Minnesota Living with Heart Failure Questionnaires were repeated during follow-up visits at 30, 90, and 180 days after treatment. During a 6-month follow-up, these tests confirmed favorable tolerability of the procedure, without device-related adverse events, serious arrhythmias, blood test abnormalities, or death. Serial echocardiographic studies showed preservation of left ventricular indices and left ventricular ejection fraction. CONCLUSIONS: This first-in-man pilot study shows that intracoronary deployment of an IK-5001 scaffold is feasible and well tolerated. Our results have promoted the initiation of a multicenter, randomized controlled trial to confirm the safety and efficacy of this new approach in high-risk patients after ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01226563.
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