Trial record 6 of 12 for:    cardiovascular febuxostat

Febuxostat for Cerebral and caRdiorenovascular Events prEvEntion stuDy (FREED)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Teijin Pharma
Information provided by (Responsible Party):
Hisao Ogawa, Freed Study Group
ClinicalTrials.gov Identifier:
NCT01984749
First received: October 30, 2013
Last updated: December 9, 2015
Last verified: December 2015
  Purpose
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.

Condition Intervention
Hyperuricemia
Drug: Febuxostat

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Comparative Trial on the Effect of Febuxostat in Preventing Cerebral and Cardiorenovascular Events in Patients With Hyperuricemia

Resource links provided by NLM:


Further study details as provided by Freed Study Group:

Primary Outcome Measures:
  • Development of cerebral or cardiorenovascular events and all deaths [ Time Frame: Enrollment through Month 36 ] [ Designated as safety issue: Yes ]

    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


Secondary Outcome Measures:
  • Occurrence of cerebral or cardiorenovascular event by event [ Time Frame: Enrollment through Month 36 ] [ Designated as safety issue: Yes ]
  • Occurrence of cerebral or cardiorenovascular event by serum uric acid level [ Time Frame: Enrollment through Month 36 ] [ Designated as safety issue: Yes ]
  • Occurrence of cerebral or cardiorenovascular event by prior history of cerebral or cardiorenovascular disease [ Time Frame: Enrollment through Month 36 ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]
  • Change in serum uric acid level [ Time Frame: Enrollment through Week 4 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Week 8 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Week 12 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 6 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 12 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 18 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 24 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 30 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in serum uric acid level [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ] [ Designated as safety issue: Yes ]
  • Percent Achieving serum uric acid level of 6.0mg/dL [ Time Frame: Enrollment to completion of study or withdrawal ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Week 4 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Week 8 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Week 12 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 6 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 12 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 18 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 24 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 30 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in eGFR [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ] [ Designated as safety issue: Yes ]
  • Urine microalbumin-creatinine ratio [ Time Frame: Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study) ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 6 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 12 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 24 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in urine microalbumin-creatinine ratio [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ] [ Designated as safety issue: Yes ]
  • Quantification of urinary protein [ Time Frame: Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study) ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in quantified urinary protein [ Time Frame: Enrollment through Month 6 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in quantified urinary protein [ Time Frame: Enrollment through Month 12 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in quantified urinary protein [ Time Frame: Enrollment through Month 24 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in quantitative urinary protein [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ] [ Designated as safety issue: Yes ]
  • Blood pressure (systolic/diastolic) [ Time Frame: Enrollment, 6, 12, 18, 24, 30, and 36 months (or withdrawal from the study) ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 6 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 12 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 18 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 24 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 30 ] [ Designated as safety issue: Yes ]
  • Amount of change and percent change in blood pressure (systolic/diastolic) [ Time Frame: Enrollment through Month 36 (or withdrawal from the study) ] [ Designated as safety issue: Yes ]
  • Occurrence of adverse events [ Time Frame: Enrollment through Month 36 ] [ Designated as safety issue: Yes ]
  • Occurrence of cerebral or cardiorenovascular events in the febuxostat group during the study period by febuxostat dose [ Time Frame: Enrollment through Month 36 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1000
Study Start Date: November 2013
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Febuxostat treatment group
Once daily after breakfast (generally within 30 minutes after eating)
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.
No Intervention: Non-febuxostat treatment group
No febuxostat treatment

  Eligibility

Ages Eligible for Study:   65 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01984749

  Show 139 Study Locations
Sponsors and Collaborators
Freed Study Group
Teijin Pharma
Investigators
Study Chair: Hisao Ogawa Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
  More Information

Responsible Party: Hisao Ogawa, Deputy Director General of the hospital, National Cerebral and Cardiovascular Center Hospital, Freed Study Group
ClinicalTrials.gov Identifier: NCT01984749     History of Changes
Other Study ID Numbers: 0078  UMIN000012134 
Study First Received: October 30, 2013
Last Updated: December 9, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Hyperuricemia
Pathologic Processes
Febuxostat
Gout Suppressants
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 28, 2016