AUGMENT-HF Study A Multicenter, Randomized Study Assessing the Efficacy of Left Ventricular Augmentation with Algisyl-LVR in the Treatment of Advanced Heart Failure Patients with Ischemic and Non-ischemic Cardiomyopathy: The AUGMENT-HF Study Stefan D. Anker, Andrew Coats, Gabriel Cristian, Dinu Dragomir, Enrico Pusineri, Luca Bettari, Maurizio Volterrani, Randall J. Lee, Hani N. Sabbah, Andy Hinson, Douglas L. Mann on behalf of the AUGMENT-HF Investigators AHA Scientific Sessions 1 Chicago 2014
AUGMENT-HF Study Disclosures The study was funded by LoneStar Heart, Inc, Laguna Hills, CA USA Douglas L. Mann • Scientific Advisory Board - Lone Star Heart, miRagen therapeutics, Lilly Corporation • Consultant – Bio Control Medical, Cardioxyl, Medtronic, Janssen • Grant Support – NIH AHA Scientific Sessions 2 Chicago 2014
AUGMENT-HF Study Background • Therapeutic options are limited for patients with advanced heart failure who become refractory to conventional pharmacological therapies • The injection of biomaterials into diseased myocardium has been shown to reduce myofiber stress, LV wall stress, restore LV geometry and improve LV function in animal models • Algisyl-LVR™ is a medical device that consists of a proprietary alginate hydrogel that is injected into the midwall of the LV, where it remains as a permanent implant that is intended to reduce LV wall stress and prevent or reverse the progression of heart failure in patients who have dilated left ventricle In a prior phase I pilot study of Algisyl-LVR TM in patients with symptomatic • heart failure undergoing CABG, there were significant improvements in cardiac function and reverse LV remodeling observed within 3 months AHA Scientific Sessions 3 Chicago 2014
AUGMENT-HF Study LV Restoration & Laplace ’ s Law The mechanism of the Algisyl-LVR TM R R h h Dilated Modified (LVR) σ σ P x R P x R = = 2h 2h AHA Scientific Sessions 4 Chicago 2014
AUGMENT-HF Study LV Restoration with Algisyl- LVR Placement of Alginate Hydrogel via a Limited Thoracotomy AHA Scientific Sessions 5 Chicago 2014
AUGMENT-HF Study Study Design and Objectives AUGMENT-HF is a multicenter prospective randomized clinical trial to evaluate the • safety and potential efficacy of Algisyl-LVR TM in patients with advanced heart failure who remain symptomatic despite being treated with optimal medical and/or device therapy • A total of 78 patients were randomized 1:1 − 40 patients randomized to Algisyl-LVR implant procedure + optimal medical therapy − 38 patients randomized to optimal medical therapy alone • 15 centers in Australia, Italy, Romania, Netherlands & Germany Primary Efficacy Endpoint • − Change in peak VO2 at 6 months assessed by blinded core lab • Primary Safety Endpoint Estimate the 30 day mortality associated with the implantation of the Algisyl-LVR TM device − AHA Scientific Sessions 6 Chicago 2014
AUGMENT-HF Study Key Inclusion Criteria • Inclusion criteria − ischemic or non-ischemic HF patients who remain symptomatic despite optimal evidence-based therapies for HF − EF ≤ 35% − Peak VO2 of 9.0 - 14.5 ml/min/kg − LVEDDi 30 to 40mm/m2 (LVEDD/BSA) − Stable, evidence-based therapy for heart failure • Exclusion criteria were typical for patients with advanced heart failure − Acceptable renal, hepatic, stroke and MI status − LV wall thickness of at least 8 mm required for implant • Peak VO2 was determined in blinded fashion by an independent core lab − Two CPX tests performed at baseline and again at 6 months with an average of the two tests values employed in analysis of the results AHA Scientific Sessions 7 Chicago 2014
AUGMENT-HF Study Participating Clinical Centers and Investigators Policlinico Umberto I Rome Rome, Italy Prof. Fabio Miraldi IRCCS Policlinico San Donato San Donato, Italy Dr. Enrico Pusineri Instituto Scientifico Univ. San Raffaele Milan, Italy Dr. Ottavio Alfieri IRCCS San Raffaele Rome, Italy Prof. Maurizio Volterrani Azienda Ospedaliera Ospedali Riuniti di Bergamo Bergamo, Italy Prof. Antonello Gavazzi Istituti Ospitalieri di Cremona Cremona, Italy Prof. Pirelli Salvatore Policlinico di Monza Monza, Italy Dr Andrea Mortara St. Antonius Ziekenhuis Nieuwegein Nieuwegein, Netherlands Dr. Benno Rensing Heart Center at the Alfred Melbourne, Australia Dr. Anthony Dart Military Hospital Bucharest, Romania Prof. Garbiel Cristian Spitalul Clinic De Urgenta MAI Bucharest, Romania Dr. Dinu Dragomir Clinica de Cardiologie Spitalul Clinic Urgenta Bucharest, Romania Dr. Sorin Stamate Herzzentrum Dresden Universitätsklinik Dresden, Germany Prof. Klaus Matschke Universitätsklinikum Ulm Ulm, Germany Prof. Robert Bauernschmitt Herz- und Diabeteszentrum Nordrhein Westfalen Bad Oeynhausen, Germany Dr. Hakim-Maibodi AHA Scientific Sessions 8 Chicago 2014
AUGMENT-HF Study Committees and Core Labs Clinical Events Committee Scientific Advisory Board Nicolas Danchin, MD (Chair) Douglas L. Mann, MD Gerasimos Filippatos, MD Stefan D. Anker, MD Andrew Coats, MD Data Safety Monitoring Committee Robert D. Dowling, MD Piotr Ponikowski, MD (Chair) Randall J. Lee, MD Arjang Ruhparwar, MD Hani N. Sabbah, PhD Sidney Goldstein, MD Tim Clayton, MSc Data Management & Statistics SOCAR Research S.A. (Nyon, CH) Core Laboratories Echocardiography - The Brigham and Women’s Hospital (Boston) Cardiopulmonary Exercise Testing - Henry Ford Hospital (Detroit) Holter - BioClinica, Inc. Cardiovascular Services (Princeton) Blood & Biomarkers – ICON Laboratory Services (Dublin, IE) AHA Scientific Sessions 9 Chicago 2014
AUGMENT-HF Study Consort Diagram 113 Patients Assessed for Eligibility 35 excluded during screening 78 eligible patients randomly allocated Algisyl-LVR Usual Care (n=40) (n=38) Withdrew prior to surgery (n=5) • LV thrombus (n=2) • Withdrew consent (n= 3) mITT 6-months 6-months • Lost to follow-up (n=0) • Lost to follow-up (n=0) • Died (n=6) • Died (n=3) • Completed as planned (n=29) • Completed as planned (n=35) AHA Scientific Sessions 10 Chicago 2014
AUGMENT-HF Study Baseline Demographics All Algisyl-LVR Usual Care (N=78) (N=40) (N=38) 62.3 ± 9.6 62.6 ± 10.0 62.1 ± 9.2 Age (Years) Gender (Male) 66 (85%) 32 (80%) 34 (90%) Ischemic HF 45 (58%) 23 (58%) 22 (58%) Non-ischemic HF 33 (42%) 17 (43%) 16 (42%) 2.9 ± 0.5 2.9 ± 0.4 2.8 ± 0.5 NYHA class - mean Class II/III/IV 14 / 58 / 5* 5 / 32 / 2* 9 / 26 / 3 25.8 ± 5.5 25.6 ± 5.6 26.0 ± 5.3 LVEF (%) 12.2 ± 1.8 12.2 ± 1.9 12.2 ± 1.8 Peak VO2 (ml/min/kg) 295 ± 83 280 ± 84 310 ± 80 6 MWT (m) Atrial fibrillation/flutter 33 (42%) 14 (35%) 19 (50%) Mitral regurgitation ≥ 3+ 38 (52%) 16 (43%) 22 (61%) Hypertension 44 (56%) 23 (58%) 21 (55%) Diabetes 30 (39%) 13 (33%) 17 (45%) Stroke (CVA) 9 (12%) 4 (10%) 5 (13%) Previous PCI or CABG 25 (32%) 13 (33%) 12 (32%) * One observation not reported AHA Scientific Sessions 11 11 Chicago 2014
AUGMENT-HF Study Baseline HF Medications All Algisyl-LVR Usual Care Medication Class (N=78) (N=40) (N=38) Diuretics 77 (99%) 39 (98%) 38 (100%) Beta-blockers 74 (95%) 37 (93%) 37 (97%) ARB/ ACE 69 (89%) 34 (85%) 35 (92%) Aldosterone antagonists 54 (69%) 29 (73%) 25 (66%) Lipid-lowering 56 (72%) 29 (73%) 27 (71%) Anti-thrombotics or Anti-platelet agents 77 (99%) 39 (98%) 38 (100%) Anti-platelet aggregation agents 52 (68%) 31 (80%) 21 (55%) AHA Scientific Sessions 12 Chicago 2014
AUGMENT-HF Study Operative Procedure Metrics for Algisyl-LVR Implant Algisyl-LVR (N=35) 190 ± 29 Mean Anesthesia duration (min) 80.5 ± 24.9 Mean Procedure duration (min) 15.5 ± 2.0 Mean Total number of Algisyl-LVR implants (injections) 4.6 ± 0.6 Mean Total volume of polymer administered (mL) 4.3 ± 7.3 Mean ICU Length of Stay (days) Median ICU Length of Stay (days) 2.0 (1.0 – 43.0) AHA Scientific Sessions 13 13 Chicago 2014
AUGMENT-HF Study Primary Endpoint – Peak VO2 15 Usual Care *P<0.014 14 Algisyl-LVR ml/min/kg 13.2 13 12.9 12.4 12.1 12.3 12 12.2 6m Tx effect [95%CI] 1.24 [0.26 - 2.23] 11 Baseline 3m 6m AHA Scientific Sessions 14 Chicago 2014
AUGMENT-HF Study Primary Endpoint - Peak VO2 mean change from baseline 1.5 *P<0.014 Usual Care 1.0 0.8 Algisyl-LVR 0.5 ml/min/kg 0.5 0.0 -0.2 -0.2 -0.5 -1.0 3m (n=60) 6m (n=56) * repeated measures mixed model AHA Scientific Sessions 15 Chicago 2014
AUGMENT-HF Study Six Minute Walk Test (6MWT) – change from baseline 150 Usual Care *P<0.001 Algisyl-LVR 100 84.7 60.8 meters 50 0 -9.6 -15.4 -50 3m (n=63) 6m (n=63) AHA Scientific Sessions 16 Chicago 2014
AUGMENT-HF Study NYHA Functional Class – change from baseline P*<0.001 The odds ratio (95% CI) of 30.24 (5.70 - 160.54)represents the odds of being in a better NYHA functional comparing Algisyl-LVR to Usual Care at 6 months AHA Scientific Sessions 17 Chicago 2014
AUGMENT-HF Study Summary of Clinical Outcomes 3 Month 6 Month Endpoint Treatment vs. Treatment vs. Control Control Peak VO2 (ml/min/kg) + 0.7 + 1.0 p value 0.014 6-MWT (m) +71 + 100 p value 0.001 - 0.6 - 0.9 NYHA Class p value 0.001 AHA Scientific Sessions 18 18 Chicago 2014
Recommend
More recommend
