Clinical trial NCT00987415: Using Allopurinol to Relieve Symptoms in Patients With Heart Failure and High Uric Acid Levels
Official title: Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Elevated Serum Uric Acid
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-10-01
Enrollment: 253
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: A Composite Clinical Endpoint (CCE) That Classifies Subject's Clinical Status as Improved, Worsened, or Unchanged.
timeFrame: 24 Weeks
Secondary outcomes:
measure: Change in Quality of Life (KCCQ).
timeFrame: Baseline to 12 weeks
measure: Change in Submaximal Exercise Capacity (6-MWT)
timeFrame: Baseline to 12 weeks
measure: Change in Quality of Life (KCCQ)
timeFrame: Baseline to 24 weeks
measure: Change in Submaximal Exercise Capacity (6-MWT)
timeFrame: Baseline to 24 weeks
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Boston
country: United States
facility: Harvard University
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals-Case Medical Center
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: Univ. of Utah Health Sciences Center
state: Utah
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Montreal PQ
country: Canada
facility: University of Montreal
Study officials:
affiliation: Harvard University
name: Eugene Braunwald, MD
role: STUDY_CHAIR
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
name: Alice Mascette, MD
role: STUDY_DIRECTOR
affiliation: Duke University
name: Adrian Hernandez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Givertz MM, Anstrom KJ, Redfield MM, Deswal A, Haddad H, Butler J, Tang WH, Dunlap ME, LeWinter MM, Mann DL, Felker GM, O'Connor CM, Goldsmith SR, Ofili EO, Saltzberg MT, Margulies KB, Cappola TP, Konstam MA, Semigran MJ, McNulty SE, Lee KL, Shah MR, Hernandez AF; NHLBI Heart Failure Clinical Research Network. Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study. Circulation. 2015 May 19;131(20):1763-71. doi: 10.1161/CIRCULATIONAHA.114.014536. Epub 2015 Apr 14.
citation: Fravel MA, Ernst ME. Management of gout in the older adult. Am J Geriatr Pharmacother. 2011 Oct;9(5):271-85. doi: 10.1016/j.amjopharm.2011.07.004. Epub 2011 Aug 17.