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

• Status: Terminated
• Trial end date: 2009-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Synvista Therapeutics, Inc

Criteria

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