Aldosterone Antagonism in Diastolic Heart Failure

NCT ID: NCT00108251

Last Updated: 2011-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2007-10-31

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.

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.

Conditions

Congestive Heart Failure; Diastole

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

placebo tablet

Group Type: PLACEBO_COMPARATOR

Eplerenone

Intervention Type: DRUG

aldosterone receptor blocker

2

eplerenone tablets

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

matching placebo

Interventions

Eplerenone

aldosterone receptor blocker

Intervention Type: DRUG

Placebo

matching placebo

Intervention Type: DRUG

Other Intervention Names

Inspra

Eligibility Criteria

Inclusion Criteria

1. 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

2. 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

3. 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

4. Able to walk at least 50 m at the time of enrollment

5. All patients will be required to be on ACE inhibitors or angiotensin receptor blockers for at least 4 weeks prior to enrollment

Exclusion Criteria

1. 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.

2. 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

3. Significant valvular heart disease, pericardial disease or severe chronic lung disease with cor pulmonale, as the cause of symptoms and signs of CHF

4. Patients with technically inadequate echocardiographic windows or patients with severe mitral annular calcification

5. Unstable angina or MI within 4 weeks prior to enrollment

6. Patient with severe peripheral vascular disease and claudication or other physical conditions that will limit the distance walked by them

7. Pregnant or lactating females

8. History of alcohol or substance abuse or history of repeated non-compliance with medications

9. History of cancer within 3 years (other than resected cutaneous basal or squamous cell carcinoma)

10. Participation in any other drug trial within 30 days prior to enrollment

11. Inability to provide informed consent

12. On drugs that are strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, nefazodone, trolandeomycin, clarithromycin, ritonavir, nelfinavir etc.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

US Department of Veterans Affairs

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anita Deswal, MD MPH MBBS

Role: PRINCIPAL_INVESTIGATOR

Michael E. DeBakey VA Medical Center

Locations

Michael E DeBakey VA Medical Center

Houston, Texas, United States

Countries

United States

References

Deswal A, Richardson P, Bozkurt B, Mann DL. Results of the Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction trial (RAAM-PEF). J Card Fail. 2011 Aug;17(8):634-42. doi: 10.1016/j.cardfail.2011.04.007. Epub 2011 May 31.

Reference Type: RESULT

PMID: 21807324 (View on PubMed)

Other Identifiers

CLIN-010-03S

Identifier Type: -

Identifier Source: org_study_id