Aldosterone Antagonism in Diastolic Heart Failure

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.

Study Overview

• Status: Completed
• Conditions: Congestive Heart Failure; Diastole
• Intervention / Treatment: Drug: Placebo; Drug: Eplerenone

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E DeBakey VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Six Minute Walk Distance from baseline to 24 weeks after randomization	change in six minute walk distance between the placebo and spironolactone group	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	change in above echocardiogtraphic measures between placebo and spironolactone group	24 weeks

Collaborators and Investigators

• Sponsor: US Department of Veterans Affairs
• Investigators: Principal Investigator: Anita Deswal, MD MPH MBBS, Michael E. DeBakey VA Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: April 14, 2005
• First Submitted That Met QC Criteria: April 14, 2005
• First Posted (Estimate): April 15, 2005

Study Record Updates

• Last Update Posted (Estimate): September 8, 2011
• Last Update Submitted That Met QC Criteria: September 7, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: exercise tolerance; Echocardiography; Heart Failure, Congestive; controlled clinical trial; Diastole; Receptors, Aldosterone
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: CLIN-010-03S