A Randomized, Controlled Study to Evaluate Algisyl-LVR™ as a Method of Left Ventricular Augmentation for Heart Failure

NCT01311791 | Completed Phase 2 DMC

• 1 other identifier: LSH-10-001
• Study Type: interventional
• Target: 78
• Locations: 6 countries
• Sites: 18

Brief 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.

Conditions

Heart Failure; Dilated Cardiomyopathy

Keywords

Left ventricular augmentation; Left ventricular restoration

Outcome Measures

Primary Outcomes (1)

• peak VO2

  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.

  6 months

Secondary Outcomes (1)

• 30 day all cause mortality

  30 days

Study Arms (2)

Algisyl-LVR

EXPERIMENTAL

Algisyl-LVR™ device (implants) administered during a surgical procedure.

Device: Algisyl-LVR

Standard Medical Therapy

ACTIVE COMPARATOR

as per protocol

Drug: Standard medical therapy

Interventions

Algisyl-LVR DEVICE

Algisyl-LVR™ device (implants) administered during a surgical procedure

Also known as: intramyocardial injections of Alginate hydrogel

Algisyl-LVR

Standard medical therapy DRUG

as defined per protocol

Also known as: evidence-based therapy for heart failure, heart failure medications, drug therapy

Standard Medical Therapy

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patients must be able and willing to give written informed consent
• The patients will be adult (age ≥ 18 years and ≤ 79 years) males or females
• The patients must be on stable, evidence-based therapy for heart failure
• \* Note: CRT or CRT-D are acceptable co-therapy, if placed \> 3 months before randomization or the investigator does not anticipate within 6 months after randomization
• The patients will have a left ventricular ejection fraction equal to or less than 35% via echocardiography, cardiac catheterization, radionuclide scan, or magnetic resonance imaging (measured within the last 30 days)
• The patients will have a left ventricular end diastolic dimension indexed to body surface area (LVEDDi) of 30 to 40mm/m2 (LVEDD/BSA) (measured within the last 30 days)
• Patients must have symptomatic heart failure with a Peak VO2 of 9.0 - 14.5 ml/min/kg (performed using a bicycle ergometer). Patients must perform two CPX tests (within 30 days of randomization and performed at least 20 hours apart) that differ by no more than 15% in the observed value for Peak VO2 and have a mean value of 9.0 - 14.5 ml/min/kg from these two tests.
• Patient's surgical risk must be considered reasonable and the evaluation of surgical risk should include review of coronary and left ventricular angiography
• If female, the patients must be (a) post-menopausal, (b) surgically sterile, or (c) using adequate birth control and have a negative serum pregnancy test within 7 days prior to administration of study device

You may not qualify if:

• Patients for whom it is planned to receive CABG, MVR, heart transplantation or LVAD within the next 6 months.
• Patients presenting with cardiogenic shock.
• Patients who have undergone a previous mid-sternotomy surgical procedure are excluded unless the surgeon's assessment is that the left sided limited thoracotomy is feasible and considered reasonable surgical risk.
• Patients presenting with a restrictive cardiomyopathy such as due to amyloidosis, sarcoidosis, or hemochromatosis
• Patient with a history of constrictive pericarditis
• Patients with a Q wave myocardial infarction (MI) within the last 30 days
• Patients with a recent history of stroke (within 60 days prior to the surgical procedure)
• A left ventricular (LV) wall thickness of the LV free-wall, at the mid-ventricular level, of less than 8 mm (screening echocardiography must confirm a minimum wall thickness of 8 mm)
• Patients with a serum creatinine \> 2.5 mg/dL
• Clinically significant liver enzyme abnormalities, i.e., AST(SGOT) and ALT (SGPT) more than 2.5 times the upper limit of normal
• History of severe COPD (i.e., FEV 1\< 1 liter or FEV1 \< 50% predicted)
• The patients will not be receiving concurrently an investigational Product in another clinical trial or have received an investigational Product in another clinical trial in the 30 days prior to enrollment
• A life expectancy of less than 1 year or any other condition that, in the opinion of the clinical investigator, might compromise any aspect of the trial

Sponsors & Collaborators

• LoneStar Heart, Inc.: lead

Study Sites (18)

Heart Center at the Alfred

Melbourne, Victoria, 3004, Australia

Location

Charité (Campus Virchov)

Berlin, Germany

Location

Charité - Universitätsmedizin Berlin (Campus Benjamin Franklin)

Berlin, Germany

Location

Herzzentrum Dresden Universitätsklinik

Dresden, Germany

Location

Universität Schleswig-Holstein Campus Kiel

Kiel, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

IRCCS Policlinico San Donato

San Donato, Milanese (MI), 20097, Italy

Location

IRCCS San Raffaele Roma

Rome, Rome, 00163, Italy

Location

Ospedali riuniti Dipartimento Cardiovascolare

Bergamo, 24128, Italy

Location

Istituti Ospitalieri di Cremona

Cremona, Italy

Location

Istituto Scientifico Universitario San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Policlinico Umberto I

Rome, 00161, Italy

Location

St. Antonius Ziekenhuis Nieuwegein

Nieuwegein, 3435 CM, Netherlands

Location

Auckland City Hospital

Auckland, 1024, New Zealand

Location

Centrului Clinic de Urgenta de Boli Cardiovasculare al Armatei

Bucharest, Romania

Location

Clinica de Cardiologie, Spitalul Clinic de Urgenta "Sf. Pantelimon"

Bucharest, Romania

Location

Spitalul Clinic De Urgenta MAI "Prof. Dr. Dimitrie Gerota"

Bucharest, Romania

Location

Related Publications (2)

• Anker SD, Coats AJ, Cristian G, Dragomir D, Pusineri E, Piredda M, Bettari L, Dowling R, Volterrani M, Kirwan BA, Filippatos G, Mas JL, Danchin N, Solomon SD, Lee RJ, Ahmann F, Hinson A, Sabbah HN, Mann DL. A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial). Eur Heart J. 2015 Sep 7;36(34):2297-309. doi: 10.1093/eurheartj/ehv259. Epub 2015 Jun 16.

  PMID: 26082085 RESULT

• Mann DL, Lee RJ, Coats AJ, Neagoe G, Dragomir D, Pusineri E, Piredda M, Bettari L, Kirwan BA, Dowling R, Volterrani M, Solomon SD, Sabbah HN, Hinson A, Anker SD. One-year follow-up results from AUGMENT-HF: a multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure. Eur J Heart Fail. 2016 Mar;18(3):314-25. doi: 10.1002/ejhf.449. Epub 2015 Nov 11.

  PMID: 26555602 RESULT

MeSH Terms

Conditions

Heart Failure; Cardiomyopathy, Dilated

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Maurizio Volterani, MD

  IRCCS San Raffaele Pisana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2011
• First Posted: March 10, 2011
• Study Start: August 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: May 1, 2016
• Last Updated: March 15, 2017

Record last verified: 2017-03

Locations

IT (7); AU (1); NZ (1); DE (5); NL (1); RO (3)