Aldosterone Antagonism in Diastolic Heart Failure

Sponsor

US Department of Veterans Affairs (U.S. Fed)

Overall Status

Completed

CT.gov ID

NCT00108251

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of this study is to determine whether eplerenone has a beneficial effect on improving exercise ability in patients with diastolic heart failure.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure Diastole	Drug: Eplerenone Drug: Placebo	Phase 4

Detailed Description

The objectives of this study are: 1) To evaluate the effect of eplerenone, an aldosterone antagonist, on intermediate functional outcomes in patients with DHF (diastolic heart failure); 2) To evaluate the effect of eplerenone, an aldosterone antagonist, on echocardiographic measures of diastolic dysfunction in patients with DHF.

The study is an double-blind, placebo-controlled study evaluating the effects of eplerenone compared to placebo in patients with DHF. A total of 48 patients with DHF will be randomized in a 1:1 ratio to 1) Placebo (n=24) or to 2) Eplerenone (n=24) in a dose of 25 mg a day for the first 2 weeks followed by uptitration to 50 mg a day for 22 weeks. The primary outcome is an improvement in functional capacity, measured by the distance covered in a 6-minute walk test. Secondary Outcomes include : Change echocardiographic measures of diastolic dysfunction, change in levels of B-type natriuretic peptide (BNP)and change in quality of life.

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Aldosterone Antagonism in Diastolic Heart Failure

Study Start Date :

Aug 1, 2004

Actual Primary Completion Date :

Sep 1, 2007

Actual Study Completion Date :

Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 placebo tablet	Drug: Eplerenone aldosterone receptor blocker Other Names: Inspra
Experimental: 2 eplerenone tablets	Drug: Placebo matching placebo

Arm

Intervention/Treatment

Placebo Comparator: 1

placebo tablet

Drug: Eplerenone

aldosterone receptor blocker

Other Names:

Inspra

Experimental: 2

eplerenone tablets

Drug: Placebo

matching placebo

Outcome Measures

Primary Outcome Measures

Change in Six Minute Walk Distance from baseline to 24 weeks after randomization [24 weeks]
change in six minute walk distance between the placebo and spironolactone group

Secondary Outcome Measures

Change in left ventricular stiffness at 24 weeks, Change in other echocardiographic measures of diastolic dysfunction at 24 weeks, Change in levels of B-type natriuretic peptide (BNP) at 24 weeks; Change in quality of life at 24 weeks [24 weeks]
change in above echocardiogtraphic measures between placebo and spironolactone group

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All patients must have DHF as defined by all 3 of the following criteria:

i)Presence of clinical heart failure for greater than or equal to 2 months before the screening visit. At the time of enrollment they should have NYHA functional class II or III heart failure symptoms such as dyspnea, fatigue on exertion, paroxysmal nocturnal dyspnea, and orthopnea.

ii)Left ventricular ejection fraction greater than or equal to 50% (by echo, radionuclide angiography or contrast angiography) within 2 months of screening iii) BNP (brain natriuretic peptide) greater than or equal to 62 pg/ml within 2 months of screening

Patients euvolemic on clinical examination. If patients are not euvolemic, all attempts will be made to achieve a euvolemic state with change in diuretic doses prior to enrollment into the study
Systolic blood pressure less than or equal to 150 mmHg and diastolic blood pressure less than or equal to 95 mmHg for 4 weeks prior to and at the time of enrollment
Able to walk at least 50 m at the time of enrollment
All patients will be required to be on ACE inhibitors or angiotensin receptor blockers for at least 4 weeks prior to enrollment

Exclusion Criteria:

Patients requiring eplerenone or spironolactone for treatment of other comorbid illnesses, e.g. ascites due to cirrhosis. Also, patients with severe hepatic impairment will not be included.
Contraindication to eplerenone therapy with creatinine > 2.5 mg/dl or serum potassium

5.0 mEq/L or creatinine clearance < 30 ml/min/1.73 m2 or intolerance to eplerenone or spironolactone in the past

Significant valvular heart disease, pericardial disease or severe chronic lung disease with cor pulmonale, as the cause of symptoms and signs of CHF
Patients with technically inadequate echocardiographic windows or patients with severe mitral annular calcification
Unstable angina or MI within 4 weeks prior to enrollment
Patient with severe peripheral vascular disease and claudication or other physical conditions that will limit the distance walked by them
Pregnant or lactating females
History of alcohol or substance abuse or history of repeated non-compliance with medications
History of cancer within 3 years (other than resected cutaneous basal or squamous cell carcinoma)
Participation in any other drug trial within 30 days prior to enrollment
Inability to provide informed consent
On drugs that are strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, nefazodone, trolandeomycin, clarithromycin, ritonavir, nelfinavir etc.