Urate Lowering Therapies and Left Ventricular Diastolic Dysfunction

April 26, 2020 updated by: Cheng-Wei Liu, National Defense Medical Center, Taiwan

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Taiwan
    • Songshan Dist.
      • Taipei, Songshan Dist., Taiwan, 105
        • Recruiting
        • Tri-Service General Hospital, Songshan Branch
        • Contact:
        • Principal Investigator:
          • Cheng-Wei Liu, MD
        • Sub-Investigator:
          • Wei-Cheng Chang, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Febuxostat 40mg
Febuxostat 40mg orally per day
Drug: Febuxostat 40 mg
Febuxostat 40 mg orally per day plus dietary control only
Other Names:
  • Feburic
Active Comparator: Benzbromarone 50mg
Benzbromarone 50mg orally per day
Drug: Benzbromarone 50mg
Benzbromarone 50mg orally per day plus dietary control only
Other Names:
  • Nogout
Other: Control
Dietary control only
Other: Control
Dietary control only

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change of average E/e'
Time Frame: At day1 and at week 12
the mean change of average E/e' in each group
At day1 and at week 12
Difference of average E/e'
Time Frame: At day1 and at week 12
the mean difference of average E/e' between among three groups
At day1 and at week 12
Automate office blood pressure (AOBP)
Time Frame: At day1 and at week 12
the mean difference of AOBP among three groups
At day1 and at week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change of xanthine oxidase activity
Time Frame: At day1 and at week 12
the mean change of xanthine oxidase activity in each group
At day1 and at week 12
Difference of xanthine oxidase activity
Time Frame: At day1 and at week 12
the mean difference of xanthine oxidase activity among three groups
At day1 and at week 12
Change of left ventricular mass index
Time Frame: At day1 and at week 12
the mean change of left ventricular mass index in each group
At day1 and at week 12
Difference of left ventricular mass index
Time Frame: At day1 and at week 12
the mean difference of left ventricular mass index among three groups
At day1 and at week 12
Change of tumor necrosis factor alpha
Time Frame: At day1 and at week 12
the mean change of tumor necrosis factor alpha in each group
At day1 and at week 12
Difference of tumor necrosis factor alpha
Time Frame: At day1 and at week 12
the mean difference of tumor necrosis factor alpha among three groups
At day1 and at week 12
Change of high-sensitivity interleukin-6
Time Frame: At day1 and at week 12
the mean change of high-sensitivity interleukin-6 in each group
At day1 and at week 12
Difference of high-sensitivity interleukin-6
Time Frame: At day1 and at week 12
the mean difference of high-sensitivity interleukin-6 among three groups
At day1 and at week 12
Change of thioredoxin
Time Frame: At day1 and at week 12
the mean change of Thioredoxin in each group
At day1 and at week 12
Difference of Thioredoxin
Time Frame: At day1 and at week 12
the mean difference of Thioredoxin among three group
At day1 and at week 12
Change of fibroblast growth factor 23
Time Frame: At day1 and at week 12
the mean Change of fibroblast growth factor 23 in each group
At day1 and at week 12
Difference of fibroblast growth factor 23
Time Frame: At day1 and at week 12
the mean difference of fibroblast growth factor 23 among three groups
At day1 and at week 12
Change of Dickkopf-related protein 3
Time Frame: At day1 and at week 12
the mean change of Dickkopf-related protein 3 in each group
At day1 and at week 12
Difference of Dickkopf-related protein 3
Time Frame: At day1 and at week 12
the mean difference of Dickkopf-related protein 3 among three groups
At day1 and at week 12
Change of galectin-3
Time Frame: At day1 and at week 12
the mean change of galectin-3 in each group
At day1 and at week 12
Difference of galectin-3
Time Frame: At day1 and at week 12
the mean difference of galectin-3 among three groups
At day1 and at week 12
Change of ST2
Time Frame: At day1 and at week 12
the mean change of ST2 in each group
At day1 and at week 12
Difference of ST2
Time Frame: At day1 and at week 12
the mean difference of ST2 among three groups
At day1 and at week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Defense Medical Center, Taiwan

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cheng-Wei Liu, M.D., 1.Tri-service General hospital, Songshan branch, Taipei, Taiwan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 11, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 23, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 28, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 26, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1-107-05-112

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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