A Randomized Double-Blind, Placebo-Controlled, Multiple-Dose Study to Evaluate the Effects of Alagebrium on Exercise in Subjects With Diastolic Heart Failure (BREAK-DHF-1)

Cardiovascular Clinical Studies

Status and phase: Terminated; Phase 2

Conditions: Diastolic Heart Failure

Treatments: Drug: Alagebrium

Study type: Interventional

Funder types: Other

Identifiers

NCT01913301

ALT-711-0530

Details and patient eligibility

About

The purpose of the study is to gather information regarding the safety and effectiveness of an investigational drug called Alagebrium when used treating Heart Failure in relation to exercise tolerance after 6 months in the trial.

Enrollment: 134 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males and females 50 years of age or older.
2. Diagnosis of diabetes OR a diagnosis of hypertension requiring therapy.
3. Echocardiographic ejection fraction ≥ 45% verified within 1 year prior to baseline, assuming no intercurrent cardiac event between the echo and screening.
4. Echocardiographic evidence of diastolic dysfunction as defined by an E/E' ≥ 12 determined within 1 year prior to baseline; sinus rhythm required at time of echo.
5. Previous hospitalization due to heart failure OR a current or previous BNP ≥ 100 pg/mL.
6. New York Heart Association (NYHA) functional class II-IV.
7. At least 1 month between hospitalization for heart failure and randomization.
8. Stable doses of heart failure medications (diuretics, ACE inhibitors, ARB's, beta-adrenergic antagonists, aldosterone antagonists) for at least 1 month prior to randomization.
9. Able to understand content of and willing to provide written informed consent.
10. Agree to use adequate contraception during the study if premenopausal. -

Exclusion criteria

1. Ejection fraction < 45%.

2. Screening Six-minute walk test > 450 meters or < 100 meters

3. Clinically significant cardiac valvular disease (mitral regurgitation (MR) > grade I, aortic insufficiency (AI) > grade 1, mitral stenosis (MS), aortic stenosis (AS)).

4. History of stroke, any sequelae of a transient ischemic attack (TIA), or reversible ischemic neurological defect (RIND) within 6 months prior to screening.

5. History of acute myocardial infarction within 6 months prior to screening.

6. Severe COPD as defined by O2 or steroid dependence.

7. History of systemic inflammatory or collagen vascular disease.

8. Active and or treated malignancies within 12 months prior to Visit 1 with the exception of basal cell carcinoma.

9. Any significant systemic illness(es) or medical condition(s) that could lead to difficulty complying with the protocol; or any concurrent condition(s) which, in the investigator's opinion, would prohibit the subject from completing the study, or would not be in the best interest of the subject.

10. Estimated glomerular filtration rate (GFR) ≤ 30 mL/min/1.73m² as calculated by Modification of Diet in Renal Disease (MDRD) study equation [MDRD = 186 X serum creatinine (mg/dl) 1.154 X years -0.203 X (0.742 if female) X (1.210 if African American)].

11. Liver function tests (SGOT and/or SGPT) > 2.5 times the upper limit of normal range.

12. Hb < 10 g/dL.

13. Use of any investigational drug(s) within 30 days prior to screening.

14. Previous exposure to alagebrium.

15. Known seropositivity for HIV or hepatitis C, or presence of hepatitis B surface antigen.

16. Pregnancy or active breast-feeding. Urine pregnancy tests will be performed on all women who are not post-menopausal for at least 1 year.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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134 participants in 1 patient group

Alagebrium

Experimental group

Treatment:

Drug: Alagebrium