The objectives of this study are: 1) To evaluate the effect of spironolactone, an aldosterone antagonist, on intermediate functional outcomes in patients with DHF (diastolic heart failure); 2) to evaluate 2 different dosing levels of spironolactone for tolerability as well as efficacy; 3) to collect feasibility data for the use of spironolactone in a large-scale clinical trial evaluating long-term outcomes in patients with DHF.

Condition	Treatment or Intervention	Phase
Congestive Heart Failure	Drug: spironolactone	Phase IV

Further Study Details: 

Primary Outcomes: Improvement in functional capacity, measured by the distance covered in a 6-minute walk test
Secondary Outcomes: Change in left ventricular stiffness measured by echocardiography as a marker of change in cardiac fibrosis; Change in quality of life; Clinical composite score at the end of the study

The study is a randomized, double-blind, placebo-controlled, clinical trial. A total of 48 patients with DHF will be randomized in a 1:2 ratio to 1) Placebo (n=16) or to 2) Spironolactone (n=32) in a dose of 25 mg a day for the first 12 weeks, followed by a dose of 50 mg a day for another 12 weeks. The average time in the trial for each randomized patient is expected to be 7 months. The primary endpoint is improvement in functional capacity, measured by the distance covered in a 6-minute walk test. The secondary endpoints include: change in left ventricular stiffness measured by echocardiography as a marker of change in cardiac fibrosis, change in quality of life and a clinical composite score at the end of the study. The primary analysis will be a comparison of the mean change from baseline in 6-minute walk distance at the final visit, between the placebo arm and the eplerenone arms. Secondary analysis will compare the secondary outcome measures at the final study visit between the placebo and eplerenone arms. To explore a dose response effect for the 25 and 50 mg dose, we will compare the 12 week results (on 25 mg eplerenone) with the 24 week results (12 weeks of 50 mg eplerenone mg a day, preceded by 12 weeks of 25 mg).

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Age > 18 years
• 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00108251

Texas
      Michael E. DeBakey VA Medical Center, Houston,  Texas,  77030,  United States; Recruiting

Study ID Numbers:  10
Record last reviewed:  April 2005
Last Updated:  April 14, 2005
Record first received:  April 14, 2005
ClinicalTrials.gov Identifier:  NCT00108251
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-05-03