Clinical trial NCT03534037: Urate Lowering Therapies and Left Ventricular Diastolic Dysfunction
Official title: The Cardiovascular Effects of Febuxostat and Benzbromarone on Left Ventricle Diastolic Dysfunction in Individuals With Metabolic Syndrome and Hyperuricemia - an Open-label Non-blinded Randomized-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hyperuricemia
Metabolic Syndrome
Left Ventricular Diastolic Dysfunction
Keywords: Serum uric acid
Metabolic syndrome
Left ventricular diastolic dysfunction
Febuxostat
Benzbromarone
Lead sponsor: National Defense Medical Center, Taiwan
Sponsor class: OTHER
First posted: 2018-05-23
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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.

Eligibility 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)

Primary outcomes:
measure: Change of average E/e'
timeFrame: At day1 and at week 12
measure: Difference of average E/e'
timeFrame: At day1 and at week 12
measure: Automate office blood pressure (AOBP)
timeFrame: At day1 and at week 12
Secondary outcomes:
measure: Change of xanthine oxidase activity
timeFrame: At day1 and at week 12
measure: Difference of xanthine oxidase activity
timeFrame: At day1 and at week 12
measure: Change of left ventricular mass index
timeFrame: At day1 and at week 12
measure: Difference of left ventricular mass index
timeFrame: At day1 and at week 12
measure: Change of tumor necrosis factor alpha
timeFrame: At day1 and at week 12
measure: Difference of tumor necrosis factor alpha
timeFrame: At day1 and at week 12
measure: Change of high-sensitivity interleukin-6
timeFrame: At day1 and at week 12
measure: Difference of high-sensitivity interleukin-6
timeFrame: At day1 and at week 12
measure: Change of thioredoxin
timeFrame: At day1 and at week 12
measure: Difference of Thioredoxin
timeFrame: At day1 and at week 12
measure: Change of fibroblast growth factor 23
timeFrame: At day1 and at week 12
measure: Difference of fibroblast growth factor 23
timeFrame: At day1 and at week 12
measure: Change of Dickkopf-related protein 3
timeFrame: At day1 and at week 12
measure: Difference of Dickkopf-related protein 3
timeFrame: At day1 and at week 12
measure: Change of galectin-3
timeFrame: At day1 and at week 12
measure: Difference of galectin-3
timeFrame: At day1 and at week 12
measure: Change of ST2
timeFrame: At day1 and at week 12
measure: Difference of ST2
timeFrame: At day1 and at week 12
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Tri-service General Hospital, songshan branch
state: Songshan Dist.
Study officials:
affiliation: 1.Tri-service General hospital, Songshan branch, Taipei, Taiwan
name: Cheng-Wei Liu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: