Urate Lowering Therapies and Left Ventricular Diastolic Dysfunction

National Defense Medical Center, Taiwan

Status and phase: Unknown; Phase 4

Conditions: Left Ventricular Diastolic Dysfunction; Hyperuricemia; Metabolic Syndrome

Treatments: Drug: Benzbromarone 50mg; Drug: Febuxostat 40 mg; Other: Control

Study type: Interventional

Funder types: Other

Identifiers

NCT03534037

1-107-05-112

Details and patient eligibility

About

Hyperuricemia is an additional risk factor for cardiovascular disease, associating with left ventricular diastolic dysfunction in individuals with metabolic syndrome. The effect of urate-lowering therapies on left ventricular diastolic dysfunction remains unclear. The study is conducted to investigate whether febuxostat or benzbromarone might improve left ventricular diastolic dysfunction in individuals with metabolic syndrome and hyperuricemia

Full description

Between 1, July 2018 and 31, Dec 2018, consecutive individuals with metabolic syndrome hyperuricemia are candidates of the present study. After the eligible candidates sign the informed consent, they will receive blood tests with a fasting time of 8 hours at least. The investigators will randomize the study participants by pre-specified random codes with a 1:1:1 ratio to the three groups. The study medication, febuxostat or benzbromarone, will be administered orally on the next day after transthoracic echocardiography is performed. The control group will only receive dietary control. All participant will receive transthoracic echocardiography and blood tests at baseline and at 3 months. The visit will be scheduled at baseline and at the 3rd month. The blood tests include high-sensitivity C-reactive protein, high-sensitivity interleukin-1 beta, high-sensitivity interleukin-6, tumor necrosis factor alpha, Dickkopf-related protein 3, galectin-3, ST2, fibroblast growth factor 23, xanthine oxidase activity, and thioredoxin.

Enrollment: 120 estimated patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (all of the four criteria)

1. Aged between 40-75 years
2. Metabolic syndrome
3. Hyperuricemia, defined as a serum uric acid level of 7 mg/dl or more in men or 6 mg/dl or more in females, with a history of hyperuricemia within a year; or a serum uric acid level of 8 mg/dl or more in men or 7 mg/dl or more in females and it is hardly expected to be modified by dietary control; or persistent hyperuricemia after dietary control for 3 months
4. Not take any of urate-lowering therapies (benzbromarone, allopurinol, or febuxostat)

Exclusion Criteria:

1. pregnancy
2. hypersensitivity to febuxostat or benzbromarone
3. acute gout
4. a history of urinary tract stone
5. chronic kidney disease stage IV or V
6. valvular heart disease with moderate or severe regurgitation
7. left ventricular ejection fraction of 40% or less
8. hypertrophic cardiomyopathy or dilated cardiomyopathy or infiltrative cardiomyopathy or constrictive cardiomyopathy
9. a history of congenital heart disease
10. a history of pulmonary hypertension
11. chronic atrial fibrillation or significant arrhythmia
12. a history of intracardiac device implantation
13. uncontrolled hypertension (systolic blood pressure > 160mm Hg or diastolic blood pressure > 100 mm Hg)
14. alanine Aminotransferase > 3 times upper limit)
15. acute infection
16. suspected or diagnosed with malignancy
17. a history of autoimmune disease
18. limited to or dependent on daily activities
19. life expectancy less than a year
20. Acute coronary syndrome or received a percutaneous coronary intervention or received a coronary artery graft bypass surgery or stroke within 3 months
21. Diabetes with insulin treatment or glucagon-like peptide 1 receptor agonist treatment
22. Anemia (hemoglobin < 11 mg/dl in mem or <10mg/dl in women)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

Febuxostat 40mg

Experimental group

Description:

Febuxostat 40mg orally per day

Treatment:

Drug: Febuxostat 40 mg

Benzbromarone 50mg

Active Comparator group

Description:

Benzbromarone 50mg orally per day

Treatment:

Drug: Benzbromarone 50mg

Control

Other group

Description:

Dietary control only

Treatment:

Other: Control