Chronic Heart Failure
Conditions
Keywords
Chronic Heart Failure
Brief 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.
Interventions
DRUGALT-711
200 mg tablet BID for 9 months.
DRUGPlacebo
200 mg tablet BID for 9 months.
Sponsors
Synvista Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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 |
Countries
United States
Outcome results
None listed