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Febuxostat for Cerebral and caRdiorenovascular Events prEvEntion stuDy (FREED)

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ClinicalTrials.gov Identifier: NCT01984749
Recruitment Status : Unknown
Verified August 2016 by Hisao Ogawa, Freed Study Group.
Recruitment status was:  Active, not recruiting
First Posted : November 15, 2013
Last Update Posted : August 26, 2016
Sponsor:
Collaborator:
Teijin Pharma Limited
Information provided by (Responsible Party):
Hisao Ogawa, Freed Study Group

Tracking Information
First Submitted Date  ICMJE October 30, 2013
First Posted Date  ICMJE November 15, 2013
Last Update Posted Date August 26, 2016
Study Start Date  ICMJE November 2013
Estimated Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2015)
Development of cerebral or cardiorenovascular events and all deaths [ Time Frame: Enrollment through Month 36 ]
Definition of "cerebral and cardiorenovascular events":
  1. Death due to cerebral or cardiorenovascular disease
  2. New or recurrent cerebrovascular disease (stroke [cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, stroke of unknown type], transient ischemic attack
  3. New or recurrent non-fatal coronary artery disease (myocardial infarction and unstable angina pectoris)
  4. Cardiac failure requiring hospitalization
  5. Arteriosclerotic disease requiring hospitalization (aortic aneurysm, aortic dissection, and arteriosclerosis obliterans)
  6. Renal impairment (development of microalbuminuria, progression to overt proteinuria, or overt proteinuria [≥ 300 mg/gCr], confirmed by two consecutive laboratory tests performed after the initiation of study treatments; doubling of serum creatinine level; and progression to ESRD)
  7. New atrial fibrillation (including paroxysmal atrial fibrillation)
  8. Deaths that are not caused by cerebral or cardiorenovascular disease
Original Primary Outcome Measures  ICMJE
 (submitted: November 7, 2013)
Development of cerebral or cardiorenovascular events [ Time Frame: Enrollment through Month 36 ]
In this study, the following are defined as "cerebral and cardiorenovascular events."
  1. Death due to cerebral or cardiorenovascular disease
  2. New or recurrent cerebrovascular disease (stroke [cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage], an transient ischemic attacks)
  3. New or recurrent non-fatal coronary artery disease (myocardial infarction and unstable angina pectoris)
  4. Cardiac failure requiring hospitalization
  5. Arteriosclerotic disease requiring hospitalization (aortic aneurysm, aortic dissection, and arteriosclerosis obliterans)
  6. Renal impairment (development of microalbuminuria or progression to overt proteinuria, doubling of serum creatinine level, and progression to ESRD)
  7. New atrial fibrillation (including paroxysmal atrial fibrillation)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2015)
  • Occurrence of cerebral or cardiorenovascular event by event [ Time Frame: Enrollment through Month 36 ]
  • Occurrence of cerebral or cardiorenovascular event by serum uric acid level [ Time Frame: Enrollment through Month 36 ]
  • Occurrence of cerebral or cardiorenovascular event by prior history of cerebral or cardiorenovascular disease [ Time Frame: Enrollment through Month 36 ]
  • Serum uric acid level [ Time Frame: At screening, at enrollment, at 4, 8, and 12 weeks and 6, 12, 18, 24, 30, and 36 months (or at withdrawal from the study) ]
  • Change in serum uric acid level [ Time Frame: Enrollment through Week 4 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Week 8 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Week 12 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 18 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 30 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • Percent Achieving serum uric acid level of 6.0mg/dL [ Time Frame: Enrollment to completion of study or withdrawal ]
  • Estimated glomerular filtration rate (eGFR) [ Time Frame: Enrollment, 4, 8, and 12 weeks and 6, 12, 18, 24, 30, and 36 months (or withdrawal from the study) ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Week 4 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Week 8 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Week 12 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 18 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 30 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • Urine microalbumin-creatinine ratio [ Time Frame: Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study) ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • Quantification of urinary protein [ Time Frame: Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study) ]
  • Amount of change and percent change in quantified urinary protein [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in quantified urinary protein [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in quantified urinary protein [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in quantitative urinary protein [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • Blood pressure (systolic/diastolic) [ Time Frame: Enrollment, 6, 12, 18, 24, 30, and 36 months (or withdrawal from the study) ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 18 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 30 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • Occurrence of adverse events [ Time Frame: Enrollment through Month 36 ]
  • Occurrence of cerebral or cardiorenovascular events in the febuxostat group during the study period by febuxostat dose [ Time Frame: Enrollment through Month 36 ]
  • Occurrence of cerebral or cardiorenovascular events in the non-febuxostat group during the study period by use of allopurinol [ Time Frame: Enrollment through Month 36 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2013)
  • Occurrence of cerebral or cardiorenovascular event by event [ Time Frame: Enrollment through Month 36 ]
  • Occurrence of cerebral or cardiorenovascular event by serum uric acid level [ Time Frame: Enrollment through Month 36 ]
  • Occurrence of cerebral or cardiorenovascular event by prior history of cerebral or cardiorenovascular disease [ Time Frame: Enrollment through Month 36 ]
  • Serum uric acid level [ Time Frame: At screening, at enrollment, at 4, 8, and 12 weeks and 6, 12, 18, 24, 30, and 36 months (or at withdrawal from the study) ]
  • Change in serum uric acid level [ Time Frame: Enrollment through Week 4 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Week 8 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Week 12 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 18 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 30 ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • Percent Achieving serum uric acid level of 6.0mg/dL [ Time Frame: Enrollment to completion of study or withdrawal ]
  • Estimated glomerular filtration rate (eGFR) [ Time Frame: Enrollment, 4, 8, and 12 weeks and 6, 12, 18, 24, 30, and 36 months (or withdrawal from the study) ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Week 4 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Week 8 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Week 12 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 18 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 30 ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • Urine microalbumin-creatinine ratio [ Time Frame: Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study) ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • Quantification of urinary protein [ Time Frame: Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study) ]
  • Amount of change and percent change in quantified urinary protein [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in quantified urinary protein [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in quantified urinary protein [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in quantitative urinary protein [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • Blood pressure (systolic/diastolic) [ Time Frame: Enrollment, 6, 12, 18, 24, 30, and 36 months (or withdrawal from the study) ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 6 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 12 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 18 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 24 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 30 ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ]
  • All deaths [ Time Frame: Enrollment through Month 36 ]
  • Occurrence of adverse events [ Time Frame: Enrollment through Month 36 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Febuxostat for Cerebral and caRdiorenovascular Events prEvEntion stuDy
Official Title  ICMJE A Multicenter, Randomized, Comparative Trial on the Effect of Febuxostat in Preventing Cerebral and Cardiorenovascular Events in Patients With Hyperuricemia
Brief Summary The purpose of this study is to demonstrate the effect of febuxostat in preventing cerebral and cardiorenovascular events in elderly patients with hyperuricemia who are at risk for cerebral and cardiorenovascular disease.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hyperuricemia
Intervention  ICMJE Drug: Febuxostat

Febuxostat will be taken once daily after breakfast (generally within 30 minutes after eating) but can be taken around the time of breakfast even if no food has been eaten. When the dose is to be increased, the principal or sub-investigator will carry out any required examinations and tests as needed.

  1. The starting dose of the investigational product (febuxostat) will be 10 mg/day.
  2. The dose will be increased to 20 mg/day at Week 4.
  3. The aim is to increase the dose to 40 mg/day at Week 8.
Study Arms  ICMJE
  • Experimental: Febuxostat treatment group
    Once daily after breakfast (generally within 30 minutes after eating)
    Intervention: Drug: Febuxostat
  • No Intervention: Non-febuxostat treatment group
    No febuxostat treatment
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 7, 2013)
1000
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • (1) Patients 65 years of age or older at enrollment who are able to visit
  • (2) Patients with hyperuricemia, who have a serum uric acid level >7.0 mg/dL and <= 9.0 mg/dL (7.0 mg/dL < serum uric acid level <= 9.0 mg/dL) within 2 months prior to enrollment
  • (3) Patients at risk for any of the cerebral or cardiorenovascular diseases in i) through iv) below (i) Previous or current history of hypertension (ii) Previous or current history of type 2 diabetes mellitus (iii) Renal disorders (30 mL/min/1.73 m2 <= eGFR < 60 mL/min/1.73 m2 within 3 months prior to enrollment) (iv) Previous history of cerebral or cardiorenovascular disease for more than 3 months prior to enrollment (stroke [cerebral hemorrhage, cerebral infarction, or subarachnoid hemorrhage], coronary artery disease, vascular disease, or cardiac failure)
  • (4) Patients who personally give written informed consent to participate in this study

Exclusion Criteria:

  • (1) Patients with gouty tophus, or patients with subjective symptoms of gouty arthritis within 1 year prior to enrollment
  • (2) Patients with a previous history of hypersensitivity to febuxostat or allopurinol
  • (3) Patients with malignant tumors
  • (4) Patients with serious kidney disease, Acute kidney disease, nephrotic syndrome, dialysis patients, kidney transplant patients, eGFR < 30 mL/min/1.73 m2 , etc.
  • (5) Patients with a previous history of acute coronary syndrome or stroke within 3 months prior to enrollment (cerebral hemorrhage, cerebral infarction, or subarachnoid hemorrhage)
  • (6) Patients with a >= 50% increase in serum creatinine within 3 months prior to enrollment
  • (7) Patients with severe hypertension characterized by systolic blood pressure >= 180 mmHg or diastolic blood pressure >= 110 mmHg within 3 months prior to enrollment
  • (8) Patients with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 2 or more times the upper limit of normal within 3 months prior to enrollment
  • (9) Patients on any of the following medications at enrollment Mercaptopurine hydrate, azathioprine, vidarabine, or didanosine
  • (10) Patients who receive any of the following medications for the treatment of hyperuricemia within 1 month prior to enrollment Allopurinol, benzbromarone, probenecid, bucolome, topiroxostat, or febuxostat
  • (11) Patients who start, modify the dose of, or discontinue any of the following medications within 1 month prior to enrollment Losartan, irbesartan, fenofibrate, thiazide diuretics, or loop diuretics
  • (12) Patients on hormone replacement therapy with estrogen (estrogenic hormone products)
  • (13) Patients who have participated in other clinical research (including trials) within 6 months prior to enrollment (non-interventional observational research not excluded)
  • (14) Patients otherwise judged by the principal or sub-investigator to be unsuitable for the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01984749
Other Study ID Numbers  ICMJE 0078
UMIN000012134 ( Registry Identifier: UMIN )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hisao Ogawa, Freed Study Group
Study Sponsor  ICMJE Freed Study Group
Collaborators  ICMJE Teijin Pharma Limited
Investigators  ICMJE
Study Chair: Hisao Ogawa Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
PRS Account Freed Study Group
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP