Cardiovascular Safety of Febuxostat and Allopurinol in Participants With Gout and Cardiovascular Comorbidities (CARES)



Status:Completed
Conditions:Gout, Peripheral Vascular Disease, Cardiology
Therapuetic Areas:Cardiology / Vascular Diseases, Rheumatology
Healthy:No
Age Range:50 - Any
Updated:6/16/2018
Start Date:April 23, 2010
End Date:July 18, 2017

Use our guide to learn which trials are right for you!

A Multicenter, Randomized, Active-Control, Phase 3B Study to Evaluate the Cardiovascular Safety of Febuxostat and Allopurinol in Subjects With Gout and Cardiovascular Comorbidities

The purpose of this study is to see whether subjects with gout who receive febuxostat or
allopurinol for up to 9 years have a higher rate of serious heart and blood vessel
complications (major cardiovascular events).

The drug tested in this study was called Febuxostat (TMX-67). Febuxostat compared with
allopurinol was evaluated for the cardiovascular (CV) safety in people with gout and
significant CV comorbidities.

The study enrolled 6198 patients. Participants with a diagnosis of gout were enrolled in a
1:1 ratio to receive either:

- Febuxostat

- Allopurinol

Participants received febuxostat 40 mg or 80 mg for the study depending on their serum uric
acid levels were either <6.0 mg/dL or ≥6.0 mg/dL during specified visits. Allopurinol 200 mg
to 400 mg (for moderate renal impairment),or 300 mg to 600 mg (for normal and mild renal
impairment), increased in 100 mg increments each month until serum uric acid was <6.0 mg/dL
was received.

This multi-center trial was conducted in Canada, Mexico and United States. The overall time
to participate in this study was approximately 7 years (84 months). Participants made
multiple visits to the clinic and were also contacted through the telephone.

Inclusion Criteria:

1. The participant or the participant's legally acceptable representative signs and dates
a written, informed consent form/Health Insurance Portability and Accountability Act
(HIPAA) Authorization prior to the initiation of any study procedures.

2. The participant is male ≥50 years of age or female ≥55 years of age and at least
2-years post-menopausal.

3. The participant has a history of major CV or cerebrovascular disease including at
least one of the following:

- Myocardial infarction (MI).

- Hospitalized unstable angina.

- Cardiac or cerebrovascular revascularization procedure.

- Stroke.

- Hospitalized transient ischemic attack (TIA).

- Peripheral vascular disease (ankle brachial index ≤0.6, revascularization and/or
well-documented history of claudication).

- History of diabetes mellitus with evidence of micro- or macrovascular disease
(retinopathy, neuropathy, nephropathy, small vessel vascular diseases).

4. The participant has a history or presence of gout defined as having one or more of the
American Rheumatism Association criteria for the diagnosis of gout:

- A tophus proven to contain urate crystals by chemical or polarized light
microscopic means, and/or

- Characteristic urate crystals in the joint fluid, and/or

- History of at least 6 of the following clinical, laboratory, and X-ray phenomena:

- More than 1 attack of acute arthritis.

- Maximum inflammation developed within 1 day.

- Monoarticular arthritis.

- Redness observed over joints.

- First metatarsophalangeal joint painful or swollen.

- Unilateral first metatarsophalangeal joint attack.

- Unilateral tarsal joint attack.

- Tophus (proven or suspected).

- Hyperuricemia.

- Asymmetric swelling within a joint on x-ray.

- Subcortical cysts without erosions on x-ray.

- Joint fluid culture negative for organisms during attack.

5. The participants must have either:

- a serum urate or serum uric acid (sUA) level ≥7.0 mg/dL (≥416 μmol/L) at the Day
-7 Visit OR

- a sUA level ≥6.0 mg/dL (≥354 μmol/L) at the Day -7 Visit AND inadequately
controlled gout (≥1 flare in the 12 months prior to screening and/or the presence
of tophi).

6. The participant is capable of understanding and complying with protocol requirements

Exclusion Criteria:

Participants who meet any of the following criteria will not qualify for entry into this
study:

1. The participant has secondary hyperuricemia (eg, due to myeloproliferative disorder,
or organ transplant).

2. The participant has a history of xanthinuria.

3. The participant has received urate-lowering therapy (i.e., febuxostat, allopurinol,
probenecid, etc.) or excluded medication during the screening period (beginning with
Day -7).

4. The participant has a known hypersensitivity to febuxostat or allopurinol or any
components of their formulation.

5. The participant has active peptic ulcer disease.

6. The participant has a history of cancer (other than basal cell carcinoma of the skin)
within 5 years prior to the first dose of study medication.

7. The participant had MI or stroke within 60 days prior to the Screening Visit.

8. The participant has alanine aminotransferase (ALT) and/or aspartate aminotransferase
(AST) values greater than 2 times the upper limit of normal (×ULN) during the
Screening period.

9. The participant has a significant medical condition and/or conditions that would
interfere with the treatment, safety, or compliance with the protocol.

10. The participant has a history of drug abuse (defined as any illicit drug use) or a
history of alcohol abuse within 5 years prior to the Screening Visit or the
participant consumes >14 alcoholic beverages per week.

11. The participant has received any investigational medicinal product within the 30 days
prior to the Screening Visit and throughout the study.

12. The participant's estimated creatinine clearance (CLcr) is <30 mL/min, where CLcr is
calculated using the Cockcroft and Gault formula based on ideal body weight (IBW),

13. The participant is an immediate family member, study site employee, or is in a
dependant relationship with a study site employee who is involved in conduct of this
study (eg, spouse, parent, child, sibling) or may consent under duress.

14. The participant is required to take excluded medications

15. The participant has a known history of infection with hepatitis B, hepatitis C, or
human immunodeficiency virus.
We found this trial at
221
sites
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
?
mi
from
Addison, IL
Click here to add this to my saved trials
?
mi
from
Akron, OH
Click here to add this to my saved trials
?
mi
from
Albuquerque, NM
Click here to add this to my saved trials
?
mi
from
Alexandria, VA
Click here to add this to my saved trials
?
mi
from
Altoona, PA
Click here to add this to my saved trials
?
mi
from
Anderson, SC
Click here to add this to my saved trials
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
?
mi
from
Arlington, VA
Click here to add this to my saved trials
Arlington Heights, Illinois 60004
?
mi
from
Arlington Heights, IL
Click here to add this to my saved trials
?
mi
from
Asheboro, NC
Click here to add this to my saved trials
?
mi
from
Ashland, OR
Click here to add this to my saved trials
?
mi
from
Athens, TN
Click here to add this to my saved trials
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
?
mi
from
Bellaire, TX
Click here to add this to my saved trials
?
mi
from
Bellevue, NE
Click here to add this to my saved trials
?
mi
from
Bend, OR
Click here to add this to my saved trials
?
mi
from
Bensalem, PA
Click here to add this to my saved trials
?
mi
from
Bethlehem, PA
Click here to add this to my saved trials
?
mi
from
Biddeford, ME
Click here to add this to my saved trials
?
mi
from
Billings, MT
Click here to add this to my saved trials
?
mi
from
Bingham Farms, MI
Click here to add this to my saved trials
?
mi
from
Bloomington, IN
Click here to add this to my saved trials
?
mi
from
Boise, ID
Click here to add this to my saved trials
?
mi
from
Bountiful, UT
Click here to add this to my saved trials
?
mi
from
Brick, NJ
Click here to add this to my saved trials
?
mi
from
Brockton, MA
Click here to add this to my saved trials
?
mi
from
Brownsburg, IN
Click here to add this to my saved trials
?
mi
from
Burke, VA
Click here to add this to my saved trials
?
mi
from
Butte, MT
Click here to add this to my saved trials
?
mi
from
Carrollton, TX
Click here to add this to my saved trials
?
mi
from
Cary, NC
Click here to add this to my saved trials
?
mi
from
Centerville, OH
Click here to add this to my saved trials
Charleston, South Carolina 29412
?
mi
from
Charleston, SC
Click here to add this to my saved trials
Charleston, South Carolina 29412
?
mi
from
Charleston, SC
Click here to add this to my saved trials
Charlotte, North Carolina 28207
?
mi
from
Charlotte, NC
Click here to add this to my saved trials
?
mi
from
Chaska, MN
Click here to add this to my saved trials
?
mi
from
Chattanooga, TN
Click here to add this to my saved trials
?
mi
from
Chattanooga, TN
Click here to add this to my saved trials
?
mi
from
Chelsea, MI
Click here to add this to my saved trials
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Clarksburg, West Virginia 26301
?
mi
from
Clarksburg, WV
Click here to add this to my saved trials
?
mi
from
Clarkson Valley, MO
Click here to add this to my saved trials
?
mi
from
Clarksville, TN
Click here to add this to my saved trials
?
mi
from
Coeur D'Alene, ID
Click here to add this to my saved trials
?
mi
from
Collierville, TN
Click here to add this to my saved trials
?
mi
from
Columbia, NC
Click here to add this to my saved trials
?
mi
from
Columbia, SC
Click here to add this to my saved trials
?
mi
from
Columbus, OH
Click here to add this to my saved trials
?
mi
from
Cumberland, MD
Click here to add this to my saved trials
?
mi
from
Cumberland, RI
Click here to add this to my saved trials
?
mi
from
Dallas, TX
Click here to add this to my saved trials
?
mi
from
Dallas, TX
Click here to add this to my saved trials
?
mi
from
Danville, VA
Click here to add this to my saved trials
?
mi
from
Dayton, OH
Click here to add this to my saved trials
?
mi
from
Dayton, OH
Click here to add this to my saved trials
?
mi
from
Decatur, GA
Click here to add this to my saved trials
?
mi
from
Delaware, OH
Click here to add this to my saved trials
?
mi
from
Detroit, MI
Click here to add this to my saved trials
?
mi
from
Detroit, MI
Click here to add this to my saved trials
Downingtown, Pennsylvania 19335
?
mi
from
Downingtown, PA
Click here to add this to my saved trials
?
mi
from
Draper, UT
Click here to add this to my saved trials
?
mi
from
Duluth, MN
Click here to add this to my saved trials
Duncansville, Pennsylvania 16635
?
mi
from
Duncansville, PA
Click here to add this to my saved trials
?
mi
from
Dunwoody, GA
Click here to add this to my saved trials
East Providence, Rhode Island 02915
?
mi
from
East Providence, RI
Click here to add this to my saved trials
?
mi
from
Edina, MN
Click here to add this to my saved trials
?
mi
from
Edina, MN
Click here to add this to my saved trials
?
mi
from
Edison, NJ
Click here to add this to my saved trials
?
mi
from
El Paso, TX
Click here to add this to my saved trials
?
mi
from
Elizabethtown, KY
Click here to add this to my saved trials
?
mi
from
Endwell, NY
Click here to add this to my saved trials
?
mi
from
Ephrata, PA
Click here to add this to my saved trials
?
mi
from
Eugene, OR
Click here to add this to my saved trials
?
mi
from
Evanston, IL
Click here to add this to my saved trials
?
mi
from
Evergreen Park, IL
Click here to add this to my saved trials
Fall River, Massachusetts 02720
?
mi
from
Fall River, MA
Click here to add this to my saved trials
?
mi
from
Fargo, ND
Click here to add this to my saved trials
?
mi
from
Fayetteville, TN
Click here to add this to my saved trials
?
mi
from
Flint, MI
Click here to add this to my saved trials
?
mi
from
Flossmoor, IL
Click here to add this to my saved trials
?
mi
from
Fort Worth, TX
Click here to add this to my saved trials
420 West 12th Avenue
Franklin, Ohio 43210
?
mi
from
Franklin, OH
Click here to add this to my saved trials
?
mi
from
Freeport, NY
Click here to add this to my saved trials
?
mi
from
Glens Falls, NY
Click here to add this to my saved trials
?
mi
from
Grand Island, NE
Click here to add this to my saved trials
?
mi
from
Grapevine, TX
Click here to add this to my saved trials
?
mi
from
Green Bay, WI
Click here to add this to my saved trials
Greensboro, North Carolina 27401
?
mi
from
Greensboro, NC
Click here to add this to my saved trials
Greenville, South Carolina 29605
?
mi
from
Greenville, SC
Click here to add this to my saved trials
Greenwood, South Carolina 29646
?
mi
from
Greenwood, SC
Click here to add this to my saved trials
?
mi
from
Greer, SC
Click here to add this to my saved trials
?
mi
from
Hagerstown, MD
Click here to add this to my saved trials
?
mi
from
Harleysville, PA
Click here to add this to my saved trials
?
mi
from
Hazelwood, MO
Click here to add this to my saved trials
?
mi
from
Henderson, NV
Click here to add this to my saved trials
?
mi
from
Honolulu, HI
Click here to add this to my saved trials
?
mi
from
Houston, TX
Click here to add this to my saved trials
?
mi
from
Houston, TX
Click here to add this to my saved trials