Clinical trial: Intensive Urate Lowering Therapy of Febuxostat Compared to Allopurinol on Cardiovascular Risk in Patients With Gout (NCT02500641)

Eligibility criteria:
Inclusion Criteria:

          1. Male or female patients 18 years and older;

          2. History of gout, flare free in the 4 weeks prior to study entry

          3. History of crystal (joint liquid) proven diagnosis or anamnestic diagnosis of gout
             according to Wallace at el. To be eligible, a subject had to present at least 6 of the
             following 12 clinical, laboratory, and x-ray phenomena:

        1. Maximum inflammation developed within 1 day, 2. More than one attack of acute arthritis,
        3. Monoarticular arthritis attack, 4. Redness observed over joints, 5. First
        metatarsophalangeal (MTP) pain or swelling, 6. Unilateral first MTP joint attack, 7.
        Unilateral tarsal joint attack, 8. Suspected or proven tophus, 9. Hyperuricemia, 10.
        Asymmetric swelling within a joint on a X ray, 11. Subcortical cysts without erosions on X
        ray, 12. Negative organisms on culture of joint fluid; 4. Naive to ULT or previously
        treated with ULT, but with no ULT treatment in the last 1 month prior to study entry and
        only if reason for ULT interruption was not due to safety concerns.

        5. Patients at study entry have elevated serum urate level >8 mg/dl. 6. Overall
        Cardiovascular (CV) risk based on the scoring proposed by the Joint Task Force of the
        European Society of Cardiology and other European Societies on cardiovascular disease
        prevention in clinical practice between 5 and 15-% (inclusive). Patients with diabetes
        mellitus type 2 could be included in the study if their CV risk score is calculated as ≤7%.

        7. Allowed concomitant medications should be maintained stable during the last 2 weeks
        before randomisation

        Exclusion Criteria:

          1. Severe chronic renal failure (creatinine clearance < 30 ml/min)

          2. Hepatic failure

          3. Active liver disease or hepatic dysfunction, defined as both alanine aminotransferase
             (ALT) and aspartate aminotransferase (AST) >2 times the upper limit of normal.

          4. Diabetes mellitus type1

          5. Life-threatening co-morbidity or with a significant medical condition and/or
             conditions that would interfere with the treatment, the safety or the compliance with
             the protocol

          6. Diagnosis of, or receiving treatment for malignancy (excluding basalioma skin cancer)
             in the previous 5 years

          7. Patients who have experienced either myocardial infarction or stroke

          8. Patients with inflammatory based arthritis (e.g.: rheumatoid arthritis, etc.)

          9. Patients with congestive heart failure, New York Heart Association (NYHA) Class III or
             IV

         10. Patients with untreated/uncontrolled thyroid function

         11. Patients with clinically severe peripheral arterial disease

         12. Concomitant administration of any of the following: azathioprine, mercaptopurine,
             theophylline, meclofenamate, sulfinpyrazone, trimethoprim-sulfamethoxazole,
             cyclophosphamide, benzbromarone, pyrazinamide, captopril and enalapril (for
             Allopurinol), tegafur, pegloticase and tacrolimus.

         13. Hypersensitivity to any one of the active substances or to any of the excipients

         14. Any contraindication to febuxostat or allopurinol (with reference to the summary of
             product characteristics).

         15. Subject is unable to take either of the protocol-required gout flare prophylactic
             medications (NSAID or colchicine) due to contraindications or intolerance, e.g.
             hypersensitivity, active gastric ulcer disease, renal impairment and/or changes in
             liver enzymes

         16. Participation in another trial of an investigational drug or device within 30 days
             prior to screening, or prior treatment with investigational product(s)

         17. Women of childbearing potential (WOCBP), including peri-menopausal women who have had
             a menstrual period within 1 year, not willing to use highly effective method of birth
             control throughout the study period and for 4 weeks after study completion defined as
             a method which results in a failure rate of less than 1% per year such as:

               -  combined (estrogen and progestogen containing) hormonal contraception associated
                  with inhibition of ovulation (oral, intravaginal, transdermal),

               -  progestogen-only hormonal contraception associated with inhibition of ovulation
                  (oral, injectable, implantable),

               -  intrauterine device (IUD),

               -  intrauterine hormone-releasing system (IUS),

               -  bilateral tubal occlusion,

               -  vasectomised partner (provided that partner is the sole sexual partner of the
                  trial participant and that the vasectomised partner has received medical
                  assessment of the surgical success),

               -  sexual abstinence;

         18. Severe psychiatric disorders/neurological disorders

         19. Severe concurrent pathology, including terminal illness (cancer, AIDS, etc)

         20. Abuse of alcohol, analgesics, or psychotropic drugs

         21. Inability or unwillingness, in the investigator's opinion, to follow study procedures
             including, but not limited to the ability to obtain adequate PWV/Pulse Wave Analysis
             (PWA) recordings. Special attention was made to any physical abnormalities which could
             affect quality of PWV/PWA measurement:

               -  Neck region- neck flexibility and accessibility of carotid artery,

               -  Upper arm and thigh region- exclude any abnormalities which would prevent
                  adequate placement of the cuff;

         22. Inability or unwillingness to issue the informed consent
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 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? Entailment