Clinical trial: Cardiovascular Safety of Febuxostat and Allopurinol in Participants With Gout and Cardiovascular Comorbidities (CARES) (NCT01101035)

Eligibility criteria:
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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 50 Years old.


Patient description (medical language): A 39-year-old man comes to the emergency department with an acute onset of severe left toe pain.  The toe is red and exhibits swelling. The patient is not febrile, and does not remember any recent trauma. Medical history is not significant except for the similar attacks and the diagnosis of gouty arthritis. His medication history includes Allopurinol to prevent gouty attacks. His father has the same medical condition. However, his older brother who is 41 years old is healthy with no history of gouty arthritis. Physical examination shows a swollen, tender first metatarsophalangeal joint.  Aspiration of the joint showed high leukocyte count, negative Gram stain, and numerous needle-shaped crystals, which is compatible with gouty arthritis.

Patient description (patient's own words): I'm a 39-year-old man and got admitted to the ER after an unbearable pain in my left toe. My toe was red and terribly swollen. I was still standing on my feet, not febrile and I don't remember hitting my head or anything. I don't have any special medical history, but I had been diagnosed with gout before. I take Lopurin to prevent my gouty attacks. My dad had the same problem, but my 41-year-old brother is healthy and does not have gouty attacks. The doctor did a physical exam and found that the joints between my toes and the rest of my foot were swollen and tender. The doctor renewed his diagnosis of gouty arthritis.

Does the patient match the trial criteria? 0