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Urate Lowering Therapies and Left Ventricular Diastolic Dysfunction

Phase 4
Conditions
Metabolic Syndrome
Hyperuricemia
Left Ventricular Diastolic Dysfunction
Interventions
Registration Number
NCT03534037
Lead Sponsor
National Defense Medical Center, Taiwan
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
120
Inclusion Criteria

Not provided

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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ControlControlDietary control only
Benzbromarone 50mgBenzbromarone 50mgBenzbromarone 50mg orally per day
Febuxostat 40mgFebuxostat 40 mgFebuxostat 40mg orally per day
Primary Outcome Measures
NameTimeMethod
Change of average E/e'At day1 and at week 12

the mean change of average E/e' in each group

Difference of average E/e'At day1 and at week 12

the mean difference of average E/e' between among three groups

Automate office blood pressure (AOBP)At day1 and at week 12

the mean difference of AOBP among three groups

Secondary Outcome Measures
NameTimeMethod
Change of xanthine oxidase activityAt day1 and at week 12

the mean change of xanthine oxidase activity in each group

Difference of xanthine oxidase activityAt day1 and at week 12

the mean difference of xanthine oxidase activity among three groups

Change of left ventricular mass indexAt day1 and at week 12

the mean change of left ventricular mass index in each group

Difference of left ventricular mass indexAt day1 and at week 12

the mean difference of left ventricular mass index among three groups

Change of tumor necrosis factor alphaAt day1 and at week 12

the mean change of tumor necrosis factor alpha in each group

Difference of tumor necrosis factor alphaAt day1 and at week 12

the mean difference of tumor necrosis factor alpha among three groups

Change of high-sensitivity interleukin-6At day1 and at week 12

the mean change of high-sensitivity interleukin-6 in each group

Difference of high-sensitivity interleukin-6At day1 and at week 12

the mean difference of high-sensitivity interleukin-6 among three groups

Change of thioredoxinAt day1 and at week 12

the mean change of Thioredoxin in each group

Difference of ThioredoxinAt day1 and at week 12

the mean difference of Thioredoxin among three group

Change of fibroblast growth factor 23At day1 and at week 12

the mean Change of fibroblast growth factor 23 in each group

Difference of fibroblast growth factor 23At day1 and at week 12

the mean difference of fibroblast growth factor 23 among three groups

Change of Dickkopf-related protein 3At day1 and at week 12

the mean change of Dickkopf-related protein 3 in each group

Difference of Dickkopf-related protein 3At day1 and at week 12

the mean difference of Dickkopf-related protein 3 among three groups

Change of galectin-3At day1 and at week 12

the mean change of galectin-3 in each group

Difference of galectin-3At day1 and at week 12

the mean difference of galectin-3 among three groups

Change of ST2At day1 and at week 12

the mean change of ST2 in each group

Difference of ST2At day1 and at week 12

the mean difference of ST2 among three groups

Trial Locations

Locations (1)

Tri-service General Hospital, songshan branch

🇨🇳

Taipei, Songshan Dist., Taiwan

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