Clinical trial NCT00739687: Safety & Efficacy of ALT-711 (Alagebrium) in Chronic Heart Failure
Official title: A Double-Blind, Placebo-Controlled, Randomized Trial Evaluating the Efficacy and Safety of Alagebrium (ALT-711) in Patients With Chronic Heart Failure
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Heart Failure
Keywords: Chronic Heart Failure
Lead sponsor: Synvista Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2008-08-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: 9 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Hospital
state: Alabama
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
Study officials:
References: