Safety & Efficacy of ALT-711 (Alagebrium) in Chronic Heart Failure (BENEFICIAL)

Synvista Therapeutics

Status and phase

Terminated

Phase 2

Conditions

Chronic Heart Failure

Treatments

Drug: ALT-711

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT00739687

ALT-711-0527a

Details and patient eligibility

About

Several lines of evidence have suggested that Advanced Glycation End-products (AGEs) play a role in the development and progression of heart failure. The AGE-crosslink breaker Alagebrium improved cardiac function and symptoms in experimental preclinical and small human heart failure studies. These results have not yet been confirmed in a randomized controlled clinical trial. Objective: to evaluate the safety and efficacy of alagebrium in subjects diagnosed with heart failure. This is a randomized, double-blind, placebo-controlled trial to assess the effects of 400 mg (2 x 100 mg bid) of alagebrium versus placebo over 9 months. 100 subjects will be studied (50 per treatment group) in approximately 6 centers. Procedures: exercise testing (VO2 max; the primary variable), ECGs and blood sampling.

Enrollment

100 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

NYHA II-IV heart failure
Echocardiographic ejection fraction ≤ 45% (echo does not need to be repeated at the screening visit if a prior echo is on record which indicates an ejection fraction < 40%)
Duration of heart failure > 3 months
Stable heart failure medical therapy for > 1 month
Patients need to be able to understand content of and willing to provide informed consent

Exclusion criteria

Patient ≤ 18 years
History of myocardial infarction in previous 6 months
History of stroke/TIA/RIND in previous 6 months
Severe valvular dysfunction
Severe pulmonary disease
History of systemic inflammatory or collagen vascular disease
Active and or treated malignancies within 12 months prior to inclusion
Any significant condition either medical or non-medical that could lead to difficulty complying with the protocol
Patients on cardiac resynchronisation therapy (CRT) or scheduled for CRT implantation
Pacemaker therapy (unless rescue pacing at ≤ 40 bpm) or scheduled pacemaker implantation
History of valve replacement or surgery
Uncontrolled diabetes mellitus (HbA1c > 9.5%)
Clinically significant renal disturbance (sMDRD calculated GFR≤30 mL/min/1.73m2; sMDRD is calculated as 186 x serum Cr (mg/dl)-1.154 x years-0.203 x (0.742 if female) x (1.210 if African American)
Clinically significant liver disease (ASAT/ALAT > 2,5 times the upper limit of normal)
Severe anemia at baseline (Hemoglobin <10 g/dl or <6.2 mmol/l)
Use of any investigational drug(s) within 30 days prior to screening
Pregnancy or active breast-feeding (urine pregnancy tests will be performed on all female subjects of childbearing potential)*
Active pericarditis/myocarditis
The inability of patients to undergo exercise testing