A Randomized, Controlled Study to Evaluate Algisyl-LVR™ as a Method of Left Ventricular Augmentation for Heart Failure
Condition: Heart Failure; Dilated Cardiomyopathy
MeSH terms: Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Algisyl-LVR; Standard medical therapy
Intervention type(s): Device; Drug
Intervention description(s): Algisyl-LVR™ device (implants) administered during a surgical procedure; as defined per protocol
Other intervention name(s): intramyocardial injections of Alginate hydrogel; evidence-based therapy for heart failure; heart failure medications; drug therapy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Left ventricular augmentation; Left ventricular restoration