Using Allopurinol to Relieve Symptoms in Patients With Heart Failure and High Uric Acid Levels

Study Overview
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Brief Summary
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The purpose of this study is to determine whether allopurinol is effective in relieving symptoms of patients with heart failure and high blood uric acid levels.

Official Title
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Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients

Conditions
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Heart Failure, Elevated Serum Uric Acid

Intervention / Treatment
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* Drug: allopurinol
* Drug: sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NYHA class II-IV heart failure due to ischemic or non-ischemic cardiomyopathy. Left ventricular ejection fraction ≤ 40% by echocardiography- Heart failure symptoms for 3 months despite standard treatment. Serum uric acid level ≥ 9.5 mg/dl. At least one of the following additional markers of increased risk: Hospitalization, ER visit or urgent clinic visit for heart failure requiring IV diuretics within the previous 12 months; Left ventricular ejection fraction ≤ 25; B-type natriuretic peptide level > 250 pg/ml Exclusion Criteria: Hypertrophic or restrictive cardiomyopathy, constrictive pericarditis, biopsy-proven myocarditis, severe stenotic valvular disease, or complex congenital heart disease. Acute coronary syndrome, PCI or CABG within 3 months. Current ventricular assist device or ventricular assist device or heart transplant likely within the next 6 months. Uncontrolled hypertension (i.e., SBP > 170 mm Hg or DBP > 110 mm Hg) Serum creatinine > 3 mg/dL or estimated GFR < 20 ml/min. Evidence of active hepatitis with ALT and AST greater than 3x normal. Any condition other than HF which could limit the ability to perform a 6-minute walk test Any diseases other than HF which are likely to alter the patient's global perception of status or quality of life over a period of 6 months. Receiving treatment with allopurinol currently or within 30 days, or having symptomatic hyperuricemia which requires treatment with allopurinol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: allopurinol<br>Allopurinol 300 mg daily for one week, then 600 mg daily to complete 24 weeks. | Drug: allopurinol<br>* Allopurinol 300 mg daily for one week, then 600 mg daily to complete 24 weeks.<br>|
| Placebo Comparator: sugar pill<br>Matching placebo 300 mg daily for one week, then 600 mg daily to complete 24 weeks. | Drug: sugar pill<br>* Matching placebo 300 mg daily for one week, then 600 mg daily to complete 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A Composite Clinical Endpoint (CCE) That Classifies Subject's Clinical Status as Improved, Worsened, or Unchanged. | CCE composed of 3-level categorical variable with options that include worsened, unchanged or improved | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life (KCCQ). | Kansas City Cardiomyopathy (KCCQ) overall summary score - The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. | Baseline to 12 weeks | 
| Change in Submaximal Exercise Capacity (6-MWT) | 6-Minute Walk Test | Baseline to 12 weeks | 
| Change in Quality of Life (KCCQ) | Kansas City Cardiomyopathy (KCCQ) overall summary score - The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. | Baseline to 24 weeks | 
| Change in Submaximal Exercise Capacity (6-MWT) | 6-Minute Walk Test | Baseline to 24 weeks |