Back to resultsUrate Lowering Therapies and Left Ventricular Diastolic Dysfunction
Primary Purpose
Hyperuricemia, Metabolic Syndrome, Left Ventricular Diastolic Dysfunction
Status
Unknown status
Phase
Phase 4
Locations
Taiwan
Study Type
Interventional
Intervention
Febuxostat 40 mg
Benzbromarone 50mg
Control
Sponsored by
About this trial
This is an interventional treatment trial for Hyperuricemia focused on measuring Serum uric acid, Metabolic syndrome, Left ventricular diastolic dysfunction, Febuxostat, Benzbromarone
Eligibility Criteria
Inclusion Criteria (all of the four criteria)
- Aged between 40-75 years
- Metabolic syndrome
- 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
- Not take any of urate-lowering therapies (benzbromarone, allopurinol, or febuxostat)
Exclusion Criteria:
- pregnancy
- hypersensitivity to febuxostat or benzbromarone
- acute gout
- a history of urinary tract stone
- chronic kidney disease stage IV or V
- valvular heart disease with moderate or severe regurgitation
- left ventricular ejection fraction of 40% or less
- hypertrophic cardiomyopathy or dilated cardiomyopathy or infiltrative cardiomyopathy or constrictive cardiomyopathy
- a history of congenital heart disease
- a history of pulmonary hypertension
- chronic atrial fibrillation or significant arrhythmia
- a history of intracardiac device implantation
- uncontrolled hypertension (systolic blood pressure > 160mm Hg or diastolic blood pressure > 100 mm Hg)
- alanine Aminotransferase > 3 times upper limit)
- acute infection
- suspected or diagnosed with malignancy
- a history of autoimmune disease
- limited to or dependent on daily activities
- life expectancy less than a year
- Acute coronary syndrome or received a percutaneous coronary intervention or received a coronary artery graft bypass surgery or stroke within 3 months
- Diabetes with insulin treatment or glucagon-like peptide 1 receptor agonist treatment
- Anemia (hemoglobin < 11 mg/dl in mem or <10mg/dl in women)
Sites / Locations
- Tri-service General Hospital, songshan branchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Other
Arm Label
Febuxostat 40mg
Benzbromarone 50mg
Control
Arm Description
Febuxostat 40mg orally per day
Benzbromarone 50mg orally per day
Dietary control only
Outcomes
Primary Outcome Measures
Change of average E/e'
the mean change of average E/e' in each group
Difference of average E/e'
the mean difference of average E/e' between among three groups
Automate office blood pressure (AOBP)
the mean difference of AOBP among three groups
Secondary Outcome Measures
Change of xanthine oxidase activity
the mean change of xanthine oxidase activity in each group
Difference of xanthine oxidase activity
the mean difference of xanthine oxidase activity among three groups
Change of left ventricular mass index
the mean change of left ventricular mass index in each group
Difference of left ventricular mass index
the mean difference of left ventricular mass index among three groups
Change of tumor necrosis factor alpha
the mean change of tumor necrosis factor alpha in each group
Difference of tumor necrosis factor alpha
the mean difference of tumor necrosis factor alpha among three groups
Change of high-sensitivity interleukin-6
the mean change of high-sensitivity interleukin-6 in each group
Difference of high-sensitivity interleukin-6
the mean difference of high-sensitivity interleukin-6 among three groups
Change of thioredoxin
the mean change of Thioredoxin in each group
Difference of Thioredoxin
the mean difference of Thioredoxin among three group
Change of fibroblast growth factor 23
the mean Change of fibroblast growth factor 23 in each group
Difference of fibroblast growth factor 23
the mean difference of fibroblast growth factor 23 among three groups
Change of Dickkopf-related protein 3
the mean change of Dickkopf-related protein 3 in each group
Difference of Dickkopf-related protein 3
the mean difference of Dickkopf-related protein 3 among three groups
Change of galectin-3
the mean change of galectin-3 in each group
Difference of galectin-3
the mean difference of galectin-3 among three groups
Change of ST2
the mean change of ST2 in each group
Difference of ST2
the mean difference of ST2 among three groups
Full Information
NCT ID
NCT03534037
First Posted
May 11, 2018
Last Updated
April 26, 2020
Sponsor
National Defense Medical Center, Taiwan
1. Study Identification
Unique Protocol Identification Number
NCT03534037
Brief Title
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
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2020 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Defense Medical Center, Taiwan
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperuricemia, Metabolic Syndrome, Left Ventricular Diastolic Dysfunction
Keywords
Serum uric acid, Metabolic syndrome, Left ventricular diastolic dysfunction, Febuxostat, Benzbromarone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Febuxostat 40mg
Arm Type
Experimental
Arm Description
Febuxostat 40mg orally per day
Arm Title
Benzbromarone 50mg
Arm Type
Active Comparator
Arm Description
Benzbromarone 50mg orally per day
Arm Title
Control
Arm Type
Other
Arm Description
Dietary control only
Intervention Type
Drug
Intervention Name(s)
Febuxostat 40 mg
Other Intervention Name(s)
Feburic
Intervention Description
Febuxostat 40 mg orally per day plus dietary control only
Intervention Type
Drug
Intervention Name(s)
Benzbromarone 50mg
Other Intervention Name(s)
Nogout
Intervention Description
Benzbromarone 50mg orally per day plus dietary control only
Intervention Type
Other
Intervention Name(s)
Control
Intervention Description
Dietary control only
Primary Outcome Measure Information:
Title
Change of average E/e'
Description
the mean change of average E/e' in each group
Time Frame
At day1 and at week 12
Title
Difference of average E/e'
Description
the mean difference of average E/e' between among three groups
Time Frame
At day1 and at week 12
Title
Automate office blood pressure (AOBP)
Description
the mean difference of AOBP among three groups
Time Frame
At day1 and at week 12
Secondary Outcome Measure Information:
Title
Change of xanthine oxidase activity
Description
the mean change of xanthine oxidase activity in each group
Time Frame
At day1 and at week 12
Title
Difference of xanthine oxidase activity
Description
the mean difference of xanthine oxidase activity among three groups
Time Frame
At day1 and at week 12
Title
Change of left ventricular mass index
Description
the mean change of left ventricular mass index in each group
Time Frame
At day1 and at week 12
Title
Difference of left ventricular mass index
Description
the mean difference of left ventricular mass index among three groups
Time Frame
At day1 and at week 12
Title
Change of tumor necrosis factor alpha
Description
the mean change of tumor necrosis factor alpha in each group
Time Frame
At day1 and at week 12
Title
Difference of tumor necrosis factor alpha
Description
the mean difference of tumor necrosis factor alpha among three groups
Time Frame
At day1 and at week 12
Title
Change of high-sensitivity interleukin-6
Description
the mean change of high-sensitivity interleukin-6 in each group
Time Frame
At day1 and at week 12
Title
Difference of high-sensitivity interleukin-6
Description
the mean difference of high-sensitivity interleukin-6 among three groups
Time Frame
At day1 and at week 12
Title
Change of thioredoxin
Description
the mean change of Thioredoxin in each group
Time Frame
At day1 and at week 12
Title
Difference of Thioredoxin
Description
the mean difference of Thioredoxin among three group
Time Frame
At day1 and at week 12
Title
Change of fibroblast growth factor 23
Description
the mean Change of fibroblast growth factor 23 in each group
Time Frame
At day1 and at week 12
Title
Difference of fibroblast growth factor 23
Description
the mean difference of fibroblast growth factor 23 among three groups
Time Frame
At day1 and at week 12
Title
Change of Dickkopf-related protein 3
Description
the mean change of Dickkopf-related protein 3 in each group
Time Frame
At day1 and at week 12
Title
Difference of Dickkopf-related protein 3
Description
the mean difference of Dickkopf-related protein 3 among three groups
Time Frame
At day1 and at week 12
Title
Change of galectin-3
Description
the mean change of galectin-3 in each group
Time Frame
At day1 and at week 12
Title
Difference of galectin-3
Description
the mean difference of galectin-3 among three groups
Time Frame
At day1 and at week 12
Title
Change of ST2
Description
the mean change of ST2 in each group
Time Frame
At day1 and at week 12
Title
Difference of ST2
Description
the mean difference of ST2 among three groups
Time Frame
At day1 and at week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (all of the four criteria)
Aged between 40-75 years
Metabolic syndrome
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
Not take any of urate-lowering therapies (benzbromarone, allopurinol, or febuxostat)
Exclusion Criteria:
pregnancy
hypersensitivity to febuxostat or benzbromarone
acute gout
a history of urinary tract stone
chronic kidney disease stage IV or V
valvular heart disease with moderate or severe regurgitation
left ventricular ejection fraction of 40% or less
hypertrophic cardiomyopathy or dilated cardiomyopathy or infiltrative cardiomyopathy or constrictive cardiomyopathy
a history of congenital heart disease
a history of pulmonary hypertension
chronic atrial fibrillation or significant arrhythmia
a history of intracardiac device implantation
uncontrolled hypertension (systolic blood pressure > 160mm Hg or diastolic blood pressure > 100 mm Hg)
alanine Aminotransferase > 3 times upper limit)
acute infection
suspected or diagnosed with malignancy
a history of autoimmune disease
limited to or dependent on daily activities
life expectancy less than a year
Acute coronary syndrome or received a percutaneous coronary intervention or received a coronary artery graft bypass surgery or stroke within 3 months
Diabetes with insulin treatment or glucagon-like peptide 1 receptor agonist treatment
Anemia (hemoglobin < 11 mg/dl in mem or <10mg/dl in women)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cheng-Wei Liu, M.D.
Phone
886-2-27642151
Ext
671401
Email
issac700319@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cheng-Wei Liu, M.D.
Organizational Affiliation
1.Tri-service General hospital, Songshan branch, Taipei, Taiwan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tri-service General Hospital, songshan branch
City
Taipei
State/Province
Songshan Dist.
ZIP/Postal Code
105
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liu, MD
Phone
+886-910682383
Email
issac700319@gmail.com
First Name & Middle Initial & Last Name & Degree
Cheng-Wei Liu, MD
First Name & Middle Initial & Last Name & Degree
Wei-Cheng Chang, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Urate Lowering Therapies and Left Ventricular Diastolic Dysfunction
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