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

Chronic Heart Failure Clinical Trial

— BENEFICIAL  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00739687
• Other study ID #: ALT-711-0527a
• Status: Terminated
• Phase: Phase 2
• First received: August 21, 2008
• Last updated: January 29, 2009
• Start date: August 2008
• Est. completion date: October 2009

Study information

• Verified date: January 2009
• Source: Synvista Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: October 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• ALT-711
200 mg tablet BID for 9 months.
• Placebo
200 mg tablet BID for 9 months.

Locations

Country	Name	City	State
United States	University of Alabama Hospital	Birmingham	Alabama
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Synvista Therapeutics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No