Aldosterone Antagonism in Diastolic Heart Failure

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00108251
First received: April 14, 2005
Last updated: September 7, 2011
Last verified: September 2011
  Purpose

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 Intervention Phase
Congestive Heart Failure
Diastole
Drug: Eplerenone
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Aldosterone Antagonism in Diastolic Heart Failure

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Change in Six Minute Walk Distance from baseline to 24 weeks after randomization [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    change in above echocardiogtraphic measures between placebo and spironolactone group


Enrollment: 48
Study Start Date: August 2004
Study Completion Date: October 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
placebo tablet
Drug: Eplerenone
aldosterone receptor blocker
Other Name: Inspra
Experimental: 2
eplerenone tablets
Drug: Placebo
matching placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00108251

Locations
United States, Texas
Michael E DeBakey VA Medical Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Anita Deswal, MD MPH MBBS Michael E DeBakey VA Medical Center
  More Information

Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00108251     History of Changes
Other Study ID Numbers: CLIN-010-03S
Study First Received: April 14, 2005
Last Updated: September 7, 2011
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
controlled clinical trial
Diastole
Echocardiography
exercise tolerance
Heart Failure, Congestive
Receptors, Aldosterone

Additional relevant MeSH terms:
Heart Failure
Heart Failure, Diastolic
Heart Diseases
Cardiovascular Diseases
Eplerenone
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 14, 2014