A Randomized, Controlled Study to Evaluate Algisyl-LVR™ as a Method of Left Ventricular Augmentation for Heart Failure (AUGMENT-HF)
This is a pilot study to evaluate the safety and efficacy of the Algisyl-LVR™ device. The purpose of this study is to investigate Algisyl-LVR™ employed as a method of left ventricular augmentation and restoration in patients with dilated cardiomyopathy. Algisyl-LVR™ will be injected into the myocardium under direct visualization during the surgical procedure.
This study will evaluate the concept that direct mid left ventricular (LV) intramyocardial injections of Alginate hydrogel implants into the free wall of the failing LV will reduce LV size, restore LV shape, lower LV wall stress and improve global LV function.
The Primary Efficacy Endpoint of the study is the change in Peak VO2 (maximum oxygen uptake) from baseline to 6 months of follow-up. The Primary Safety Endpoint of the study is to estimate the 30 day mortality associated with the implantation of the Algisyl-LVR device
The hypothesis of the study is that there is a statistically significant difference in change in Peak VO2 from baseline to 6 month follow-up when the medically managed arm is compared to the Algisyl-LVR arm, i.e. the Algisyl LVR arm is superior to medical management.
Drug: Standard medical therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Controlled Study to Evaluate the Safety and Cardiovascular Effects of Algisyl-LVR™ as a Method of Left Ventricular Augmentation in Patients With Dilated Cardiomyopathy (AUGMENT-HF)|
- peak VO2 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]The primary effectiveness endpoint will be a comparison of change in Peak VO2 from baseline to 6 months of follow-up between the Algisyl-LVR and medically managed arms with the intention to prove superiority in improvement in Peak VO2 associated with the Algisyl-LVR study group as compared to the medically managed study group. Evaluation of the cardiopulmonary exercise testing will be conducted by a central, blinded core laboratory.
- 30 day all cause mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]The primary safety objective is to estimate the 30 day cardiac mortality associated with the implantation of the Algisyl-LVR device and qualitatively compare the observed rate to literature estimates for similar patients undergoing cardiac surgeries comparable in risk to implantation of the Algisyl-LVR
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||April 2016|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Algisyl-LVR™ device (implants) administered during a surgical procedure.
Algisyl-LVR™ device (implants) administered during a surgical procedure
Other Name: intramyocardial injections of Alginate hydrogel
Active Comparator: Standard Medical Therapy
as per protocol
Drug: Standard medical therapy
as defined per protocol
This is a prospective, randomized, parallel group evaluation of the safety and effectiveness of Algisyl-LVR in patients with dilated cardiomyopathy of either ischemic or non-ischemic origin. The evaluation for primary efficacy endpoint (Peak VO2) at 6 months will be investigator-blinded. The primary safety endpoint, while not blinded, is 30 day all-cause mortality and an objective assessment. The remaining study endpoints will evaluate the effects of the device through the evaluation of functional, structural, biochemical, and electrocardiographic evaluations at 6 and 12 months. Evaluation of adverse events and these assessments will also provide evidence of the safety profile of the device in patients with dilated cardiomyopathy.
Pre-enrollment baseline patient evaluation will include clinical assessment, assessment of New York Heart Association (NYHA) functional class, blood tests, chest x-ray, echocardiography, magnetic resonance imaging (MRI), electrocardiogram, cardiopulmonary exercise testing, submaximal exercise testing, and quality of life assessments. Blinded central evaluation will be performed for measures of cardiopulmonary exercise testing, blood tests, Holter Monitors and cardiac imaging.
After written patient informed consent has been obtained and verification of eligibility, patients who meet the selection criteria will be randomized. All patients must be on stable, evidence-based therapy for heart failure. Patients assigned to the Investigational Device group will have the Algisyl-LVR™ device (implants) administered during a surgical procedure. For patients randomized to the investigational device group, the investigator will make every attempt to minimize the time between randomization and surgery (i.e, no more than 7 to 10 days). Patients will be considered part of the study cohort as soon as they have been randomly allocated to either the Treatment or Control group. This time point will also be considered as the start of follow-up. For patients allocated to the Investigational Device group, the starting point of follow-up for surgical mortality and surgical complications will start as of the date when the surgical procedure is performed (or attempted). The acute response to device implant will be monitored intraoperatively via continuous electrocardiographic cardiac monitoring, arterial pressure lines, transesophageal echocardiography (TEE), and pulmonary artery catheter. Patients receiving the investigational device are expected to remain hospitalized for 5 to 14 days. Patients assigned to the control group will continue on standard medical therapy (without the investigational device).
Follow-up in this study is divided into two phases. During the first phase, referred to as the "efficacy phase", repeat testing of patient functional and cardiac structural parameters will be conducted at follow-up visits scheduled at 3 months and 6 months, and every 6 months thereafter. Follow-up testing will be supplemented by a 30 day (post randomization) telephone contact with all patients. The efficacy phase of the trial will end on a common closing date after a minimum of 6 months of follow-up (i.e., after the last patient enrolled has been completed the 6 month visit). At that point data analysis will be performed and an initial study report will be generated. Following completion of the efficacy phase, long-term monitoring will continue through each patient's 24-month visit. This second phase is referred to as the "extended follow-up phase". During this phase, data collection will be focused on long-term safety and will be conducted at 6-month intervals.
Patient's randomized to the control group and completing the 12 month visit will be provided the option of enrolling in Clinical Study LSH-11-001: An Open Label Rollover Trial for Patients Randomized to the Control Group of Study LSH-10-001. Patients must continue to meet the inclusion and exclusion criteria as stated in Study LSH-10-001 to be eligible for Study LSH-11-001.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01311791
|Heart Center at the Alfred|
|Melbourne, Victoria, Australia, 3004|
|Charité (Campus Virchov)|
|Charité - Universitätsmedizin Berlin (Campus Benjamin Franklin)|
|Herzzentrum Dresden Universitätsklinik|
|Universität Schleswig-Holstein Campus Kiel|
|IRCCS Policlinico San Donato|
|San Donato, Milanese (MI), Italy, 20097|
|Ospedali riuniti Dipartimento Cardiovascolare|
|Bergamo, Italy, 24128|
|Istituti Ospitalieri di Cremona|
|Istituto Scientifico Universitario San Raffaele|
|Milan, Italy, 20132|
|Azienda Ospedaliera di Padova|
|Padova, Italy, 35128|
|Policlinico Umberto I|
|Rome, Italy, 00161|
|IRCCS San Raffaele Roma|
|Rome, Italy, 00163|
|St. Antonius Ziekenhuis Nieuwegein|
|Nieuwegein, Netherlands, 3435 CM|
|Auckland City Hospital|
|Auckland, New Zealand, 1024|
|Centrului Clinic de Urgenta de Boli Cardiovasculare al Armatei|
|Clinica de Cardiologie, Spitalul Clinic de Urgenta "Sf. Pantelimon"|
|Spitalul Clinic De Urgenta MAI "Prof. Dr. Dimitrie Gerota"|
|Principal Investigator:||Maurizio Volterani, MD||IRCCS San Raffaele Pisana|