Urate Lowering Therapies and Left Ventricular Diastolic Dysfunction

Metabolic Syndrome Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03534037
• Other study ID #: 1-107-05-112
• Status: Recruiting
• Phase: Phase 4
• Start date: February 1, 2020
• Est. completion date: December 2021

Study information

• Verified date: April 2020
• Source: National Defense Medical Center, Taiwan
• Contact: Cheng-Wei Liu, M.D.
• Phone: 886-2-27642151
• Email: issac700319[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hyperuricemia
• Left Ventricular Diastolic Dysfunction
• Metabolic Syndrome
• Syndrome
• Ventricular Dysfunction, Left

Intervention

Drug:
• Febuxostat 40 mg
Febuxostat 40 mg orally per day plus dietary control only
• Benzbromarone 50mg
Benzbromarone 50mg orally per day plus dietary control only

Other:
• Control
Dietary control only

Locations

Country	Name	City	State
Taiwan	Tri-service General Hospital, songshan branch	Taipei	Songshan Dist.

Sponsors (1)

Lead Sponsor	Collaborator
National Defense Medical Center, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of average E/e'	the mean change of average E/e' in each group	At day1 and at week 12
Primary	Difference of average E/e'	the mean difference of average E/e' between among three groups	At day1 and at week 12
Primary	Automate office blood pressure (AOBP)	the mean difference of AOBP among three groups	At day1 and at week 12
Secondary	Change of xanthine oxidase activity	the mean change of xanthine oxidase activity in each group	At day1 and at week 12
Secondary	Difference of xanthine oxidase activity	the mean difference of xanthine oxidase activity among three groups	At day1 and at week 12
Secondary	Change of left ventricular mass index	the mean change of left ventricular mass index in each group	At day1 and at week 12
Secondary	Difference of left ventricular mass index	the mean difference of left ventricular mass index among three groups	At day1 and at week 12
Secondary	Change of tumor necrosis factor alpha	the mean change of tumor necrosis factor alpha in each group	At day1 and at week 12
Secondary	Difference of tumor necrosis factor alpha	the mean difference of tumor necrosis factor alpha among three groups	At day1 and at week 12
Secondary	Change of high-sensitivity interleukin-6	the mean change of high-sensitivity interleukin-6 in each group	At day1 and at week 12
Secondary	Difference of high-sensitivity interleukin-6	the mean difference of high-sensitivity interleukin-6 among three groups	At day1 and at week 12
Secondary	Change of thioredoxin	the mean change of Thioredoxin in each group	At day1 and at week 12
Secondary	Difference of Thioredoxin	the mean difference of Thioredoxin among three group	At day1 and at week 12
Secondary	Change of fibroblast growth factor 23	the mean Change of fibroblast growth factor 23 in each group	At day1 and at week 12
Secondary	Difference of fibroblast growth factor 23	the mean difference of fibroblast growth factor 23 among three groups	At day1 and at week 12
Secondary	Change of Dickkopf-related protein 3	the mean change of Dickkopf-related protein 3 in each group	At day1 and at week 12
Secondary	Difference of Dickkopf-related protein 3	the mean difference of Dickkopf-related protein 3 among three groups	At day1 and at week 12
Secondary	Change of galectin-3	the mean change of galectin-3 in each group	At day1 and at week 12
Secondary	Difference of galectin-3	the mean difference of galectin-3 among three groups	At day1 and at week 12
Secondary	Change of ST2	the mean change of ST2 in each group	At day1 and at week 12
Secondary	Difference of ST2	the mean difference of ST2 among three groups	At day1 and at week 12