Intensive Urate Lowering Therapy With Febuxostat in Comparison With Allopurinol on Cardiovascular Risk in Patients With Gout

Condition(s) targeted: Gout

Intervention: Febuxostat 80/120mg/day (Drug); Allopurinol 100 up to 600mg/day (Drug); Colchicine (Drug); Naproxen (Drug); Omeprazole (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Menarini International Operations Luxembourg SA

Overall contact:
Menarini Corporate Medical Department, Phone: +3905556801

Comparison of the effects of Febuxostat and Allopurinol on Pulse Wave Velocity (PWV) after 36 weeks of treatment.

Official title: The Effect of Intensive Urate Lowering Therapy (ULT) With Febuxostat in Comparison With Allopurinol on Cardiovascular Risk in Patients With Gout Using Surrogate Markers: a Randomized, Controlled Trial

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Pulse Wave Velocity

Secondary outcome:

Changes in BNP and NTproBNP values

Changes in inflammation markers

Changes in oxidative stress parameters

Changes in lipid profile

Percentage of gout patients with a serum Urate concentration of less than 6 mg/dl

Time to achieve sUA target levels for patients stratified for sUA levels at baseline as follows: 8.1-8.8 mg/dl, 8.9-9.6 mg/dl, 9.7-10.3 mg/dl, 10.4-11.00 mg/dl, >11 mg/dl

Changes in eGFR with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula

Changes in urine albumin excretion as evaluated by first morning urine albumin/creatinine ratio (mg/g)

Percentage of patients above the sUA target levels

Tender and swollen joint count

Pulse Wave Analysis

Changes in endothelial activation/adhesion markers

Number of participants with adverse events as a measure of Safety and Tolerability

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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. Preliminary criteria for the classification of the acute arthritis of primary gout; Arthritis Rheum, 1977 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 factor 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%. 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 ALT and 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. 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 22. Inability or unwillingness to issue the informed consent

Menarini Corporate Medical Department, Phone: +3905556801

Dresden, Germany; Not yet recruiting

Budapest, Hungary; Not yet recruiting

Kistarcsa, Hungary; Not yet recruiting

Avezzano, Italy; Not yet recruiting

Bologna, Italy; Not yet recruiting

Brescia, Italy; Not yet recruiting

Chieti, Italy; Not yet recruiting

Coppito, Italy; Not yet recruiting

Florence, Italy; Not yet recruiting

Milan, Italy; Not yet recruiting

Turin, Italy; Not yet recruiting

Amsterdam, Netherlands; Not yet recruiting

Grudziadz, Poland; Not yet recruiting

Krakow, Poland; Not yet recruiting

Lodz, Poland; Not yet recruiting

Warsaw, Poland; Not yet recruiting

Bucarest, Romania; Not yet recruiting

Craiova, Judet Dolj, Romania; Not yet recruiting

Timisoara, Romania; Not yet recruiting

Belgrade, Serbia; Not yet recruiting

Starting date: July 2015
Last updated: July 15, 2015