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

Study Overview
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Brief Summary
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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.

Official Title
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A Double-Blind, Placebo-Controlled, Randomized Trial Evaluating the Efficacy and Safety of Alagebrium (ALT-711) in Patients With Chronic Heart Failure

Conditions
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Chronic Heart Failure

Intervention / Treatment
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* Drug: ALT-711
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALT-711<br>Alagebrium 200 mg BID | Drug: ALT-711<br>* 200 mg tablet BID for 9 months.<br>* Other names: Alagebrium;|
| Experimental: Placebo<br>Placebo | Drug: Placebo<br>* 200 mg tablet BID for 9 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end-point of the study will be aerobic capacity (VO2 max) measured at exercise testing. An improvement of 15% in VO2 max will be considered as a clinically significant increase. |  | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Heart Failure