Elevated Serum Uric Acid, Heart Failure
Conditions
Brief summary
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.
Interventions
DRUGallopurinol
Allopurinol 300 mg daily for one week, then 600 mg daily to complete 24 weeks.
DRUGsugar pill
Matching placebo 300 mg daily for one week, then 600 mg daily to complete 24 weeks.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A Composite Clinical Endpoint (CCE) That Classifies Subject's Clinical Status as Improved, Worsened, or Unchanged. | 24 Weeks | CCE composed of 3-level categorical variable with options that include worsened, unchanged or improved |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life (KCCQ). | Baseline to 12 weeks | 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. |
| Change in Submaximal Exercise Capacity (6-MWT) | Baseline to 12 weeks | 6-Minute Walk Test |
| Change in Quality of Life (KCCQ) | Baseline to 24 weeks | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Allopurinol Allopurinol 300 mg daily for one week, then 600 mg daily to complete 24 weeks.
allopurinol: Allopurinol 300 mg daily for one week, then 600 mg daily to complete 24 weeks. | 128 |
| Sugar Pill Matching placebo 300 mg daily for one week, then 600 mg daily to complete 24 weeks.
sugar pill: Matching placebo 300 mg daily for one week, then 600 mg daily to complete 24 weeks. | 125 |
| Total | 253 |
Baseline characteristics
| Characteristic | Total | Allopurinol | Sugar Pill |
|---|---|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 13.6 | 62.1 years STANDARD_DEVIATION 14.2 | 61.8 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 250 Participants | 126 Participants | 124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 74 Participants | 32 Participants | 42 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 169 Participants | 91 Participants | 78 Participants |
| Region of Enrollment Canada | 69 participants | 36 participants | 33 participants |
| Region of Enrollment United States | 184 participants | 92 participants | 92 participants |
| Sex: Female, Male Female | 45 Participants | 18 Participants | 27 Participants |
| Sex: Female, Male Male | 208 Participants | 110 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 88 / 128 | 64 / 125 |
| serious Total, serious adverse events | 25 / 128 | 19 / 125 |
Outcome results
Primary
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
Time frame: 24 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Allopurinol | A Composite Clinical Endpoint (CCE) That Classifies Subject's Clinical Status as Improved, Worsened, or Unchanged. | Worsened | 58 participants |
| Allopurinol | A Composite Clinical Endpoint (CCE) That Classifies Subject's Clinical Status as Improved, Worsened, or Unchanged. | Unchanged | 54 participants |
| Allopurinol | A Composite Clinical Endpoint (CCE) That Classifies Subject's Clinical Status as Improved, Worsened, or Unchanged. | Improved | 16 participants |
| Sugar Pill | A Composite Clinical Endpoint (CCE) That Classifies Subject's Clinical Status as Improved, Worsened, or Unchanged. | Worsened | 58 participants |
| Sugar Pill | A Composite Clinical Endpoint (CCE) That Classifies Subject's Clinical Status as Improved, Worsened, or Unchanged. | Unchanged | 43 participants |
| Sugar Pill | A Composite Clinical Endpoint (CCE) That Classifies Subject's Clinical Status as Improved, Worsened, or Unchanged. | Improved | 24 participants |
Secondary
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.
Time frame: Baseline to 24 weeks
Population: Participants analyzed included those patients who had complete data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Allopurinol | Change in Quality of Life (KCCQ) | 1.13 units on a scale | Standard Deviation 18.89 |
| Sugar Pill | Change in Quality of Life (KCCQ) | 4.68 units on a scale | Standard Deviation 21.02 |
Secondary
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.
Time frame: Baseline to 12 weeks
Population: Participants analyzed included those patients who had complete data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Allopurinol | Change in Quality of Life (KCCQ). | 4.45 units on a scale | Standard Deviation 15.42 |
| Sugar Pill | Change in Quality of Life (KCCQ). | 3.38 units on a scale | Standard Deviation 19.43 |
Secondary
Change in Submaximal Exercise Capacity (6-MWT)
6-Minute Walk Test
Time frame: Baseline to 12 weeks
Population: Participants analyzed included those patients who had complete data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Allopurinol | Change in Submaximal Exercise Capacity (6-MWT) | 9.5 meters | Standard Deviation 77.2 |
| Sugar Pill | Change in Submaximal Exercise Capacity (6-MWT) | 9.5 meters | Standard Deviation 83.5 |
Secondary
Change in Submaximal Exercise Capacity (6-MWT)
6-Minute Walk Test
Time frame: Baseline to 24 weeks
Population: Participants analyzed included those patients who had complete data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Allopurinol | Change in Submaximal Exercise Capacity (6-MWT) | 18.1 meters | Standard Deviation 86.4 |
| Sugar Pill | Change in Submaximal Exercise Capacity (6-MWT) | 20.7 meters | Standard Deviation 86 |