Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure (The RELAX Study)
Condition: Heart Failure
MeSH terms: Heart Failure; Heart Failure, Diastolic
Intervention: Placebo; Sildenafil
Intervention MeSH terms: Sildenafil Citrate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 216.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Heart Failure, Diastolic; Decompensated Heart Failure; Sildenafil; Exercise Capacity

Summary:

      Diastolic heart failure (DHF), which affects older individuals and women at a
      disproportionate rate, is a condition that can lead to shortness of breath and fluid build-up
      in the lungs. This study will evaluate the effectiveness of the medication sildenafil at
      improving exercise ability and health outcomes in people with DHF.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previous clinical diagnosis of heart failure with current New York Heart Association
             (NYHA) Class II-IV symptoms

          -  Has experienced at least one of the following in the 12 months before study entry:

               -  Hospitalization for decompensated heart failure

               -  Acute treatment with intravenous loop diuretic or hemofiltration

               -  Mean pulmonary capillary wedge pressure greater than 15 mm Hg or left ventricular
                  end diastolic pressure (LVEDP) greater than 18 mm Hg at catheterization for
                  dyspnea

               -  Long term treatment with a loop diuretic and chronic diastolic dysfunction on
                  echocardiography, as determined by left atrial enlargement

          -  Left ventricular ejection fraction greater than or equal to 50%, as determined by a
             clinical echocardiogram or ventriculogram in the 12 months before study entry

          -  Receiving stable medical therapy in the 30 days before study entry, as determined by
             no addition or removal of angiotensin converting enzyme inhibitor (ACE), angiotensin
             receptor blocker (ARB), beta-blockers, or calcium channel blockers (CCB) and no change
             in dosage of ACE, ARBs, beta-blockers, or CCBs of more than 100%

        Exclusion Criteria:

          -  Has a neuromuscular, orthopedic, or other non-cardiac condition that prevents
             individual from exercise testing on a bicycle ergometer or from walking in a hallway

          -  Non-cardiac condition that limits life expectancy to less than 1 year at the time of
             study entry, based on the judgment of the physician

          -  Current or anticipated future need for nitrate therapy

          -  Valve disease (i.e., greater than mild aortic or mitral stenosis; greater than
             moderate aortic or mitral regurgitation)

          -  Hypertrophic cardiomyopathy

          -  Infiltrative or inflammatory myocardial disease (e.g., amyloid, sarcoid)

          -  Pericardial disease

          -  Primary pulmonary arteriopathy

          -  Has experienced a heart attack or unstable angina, or has undergone percutaneous
             transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) in
             the 60 days before study entry, or requires either PTCA or CABG at the time of study
             entry

          -  Other clinically important causes of dyspnea, such as morbid obesity or significant
             lung disease, as defined by clinical judgment or use of steroids or oxygen for lung
             disease

          -  Systolic blood pressure less than 110 mm Hg or greater than 180 mm Hg

          -  Diastolic blood pressure less than 40 mm Hg or greater than 100 mm Hg

          -  Resting heart rate (HR) greater than 100 bpm

          -  History of reduced ejection fraction (less than 50%)

          -  Implanted metallic device that will interfere with MRI examination (in people without
             atrial fibrillation)

          -  Severe kidney dysfunction (estimated glomerular filtration rate [GFR] less than 20
             ml/min/1.73m2 by modified modification of diet in renal disease [MDRD] equation)

          -  Pregnant or not using an effective form of contraception

          -  Hemoglobin level of less than 10 g/dL

          -  Taking alpha antagonists or cytochrome P450 3A4 inhibitors (e.g., ketoconazole,
             itraconazole, erythromycin, saquinavir, cimetidine, or serum protease inhibitors for
             HIV)

          -  Retinitis pigmentosa, previous diagnosis of nonischemic optic neuropathy, untreated
             proliferative retinopathy, or unexplained visual disturbance

          -  Sickle cell anemia, multiple myeloma, leukemia, or penile deformities that increase
             the risk for priapism (e.g., angulation, cavernosal fibrosis, Peyronie's disease)

          -  Severe liver disease (aspartate aminotransferase [AST] level greater than three times
             the normal limit, alkaline phosphatase or bilirubin greater than two times the normal
             limit)

          -  In being consistent with American College of Cardiology (ACC)/American Heart
             Association (AHA) guidelines, people with dyspnea and risk factors for coronary artery
             disease should have had a stress test and those people with a clinically indicated
             stress test demonstrating significant ischemia in the 1 year before study entry will
             be excluded.

          -  Listed for heart transplantation