Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function
Condition: Cardiovascular Diseases; Heart Diseases; Heart Failure, Congestive
MeSH terms: Heart Failure; Cardiovascular Diseases; Heart Diseases
Intervention: Spironolactone; Placebo
Intervention description: Spironolactone (an aldosterone antagonist) is supplied as 15 mg tablets. Drug is taken orally by subjects. The initial study drug dose is 15 mg/day (one tablet) and may be titrated up to 30 mg/day (two tablets) or 45 mg/day (three tablets). Subjects are on study drug for the duration of the trial.; Placebo of spironolactone
Intervention MeSH terms: Spironolactone; Mineralocorticoid Receptor Antagonists
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 3445.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Heart Failure; Diastolic Heart Failure; Preserved Ejection Fraction

Summary:

      The purpose of this study is to evaluate the effectiveness of aldosterone antagonist therapy
      in reducing cardiovascular mortality, aborted cardiac arrest, and heart failure
      hospitalization in patients who have heart failure with preserved systolic function.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Heart failure as defined by at least one of symptom (paroxysmal nocturnal dyspnea;
             orthopnea; or dyspnea on mild or moderate exertion) at the time of screening and at
             least one sign (any rales post cough; jugular venous pressure(JVP) greater than or
             equal to 10cm of water(H2O); lower extremity edema; or chest x-ray demonstrating
             pleural effusion, pulmonary congestion, or cardiomegaly) within 12 months prior to
             study entry:

          -  left ventricular ejection fraction greater than or equal to 45% (per local reading);
             the ejection fraction must have been obtained within 6 months prior to randomization
             and after any MI or other event that would affect ejection fraction

          -  Controlled systolic blood pressure(BP), defined as a target systolic BP less than 140
             mm Hg; participants with BP up to and including 160 mm Hg are eligible for enrollment
             if they are on three or more medications to control BP

          -  Serum potassium less than 5.0 mmol/L prior to randomization

          -  At least one hospital admission for which heart failure was a major component of the
             hospitalization some time within the 12 months prior to study entry OR brain
             natriuretic peptide (BNP) greater than or equal to 100pg/ml or N-terminal pro-BNP
             greater than or equal to 360pg/ml within the 60 days prior to study entry

          -  Women of child-bearing potential must have a negative serum/urine pregnancy test
             within 72 hours prior to randomization, must not be lactating, and must agree to use
             an effective method of contraception during the entire course of study participation

          -  Willing to comply with scheduled visits

          -  Informed consent form signed by the subject prior to participation in the trial

        EXCLUSION CRITERIA:

          -  Severe systemic illness with an expected life expectancy of less than 3 years

          -  Chronic pulmonary disease requiring home O2, oral steroid therapy, or hospitalization
             for exacerbation within 12 months of study entry, or significant chronic pulmonary
             disease in the opinion of the investigator

          -  Known infiltrative or hypertrophic obstructive cardiomyopathy or known pericardial
             constriction

          -  Primary hemodynamically significant uncorrected valvular heart disease, obstructive or
             regurgitant, or any valvular disease expected to lead to surgery during the trial

          -  Atrial fibrillation with a resting heart rate greater than 90 bpm

          -  MI in the past 90 days

          -  Coronary artery bypass graft surgery in the past 90 days

          -  Percutaneous coronary intervention in the past 30 days

          -  Heart transplant recipient

          -  Currently implanted left ventricular assist device

          -  Stroke in past 90 days

          -  Systolic BP (SBP) greater than 160 mm Hg

          -  Known orthostatic hypotension

          -  Gastrointestinal disorder that could interfere with study drug absorption

          -  Use of any aldosterone antagonist or potassium sparing medication in the last 14 days
             or any known condition that would require the use of an aldosterone antagonist during
             study participation;

          -  Known intolerance to aldosterone antagonists

          -  Current lithium use

          -  Current participation (including prior 30 days) in any other therapeutic trial

          -  Any condition that, in the opinion of the investigator, may prevent the participant
             from adhering to the trial protocol

          -  History of hyperkalemia (serum potassium greater than or equal to 5.5mmol/L) in the
             past 6 months or serum potassium greater than or equal to 5.0mmol/L within the past 2
             weeks

          -  Severe renal dysfunction, defined as an estimated glomerular filtration rate(GFR) less
             than 30ml/min. Participants with serum creatinine greater than or equal to 2.5mg/dl
             are also excluded even if their GFR is greater than or equal to 30ml/min

          -  Known chronic hepatic disease, defined as aspartate aminotransferase(AST) and alanine
             aminotransferase(ALT) levels greater than 3.0 times the upper limit of normal as read
             at the local lab.