Overview

This trial is active, not recruiting.

Condition gout
Treatments febuxostat 80/120mg/day, allopurinol 100 up to 600mg/day, colchicine, naproxen, omeprazole
Phase phase 4
Sponsor Menarini International Operations Luxembourg SA
Start date July 2015
End date November 2016
Trial size 182 participants
Trial identifier NCT02500641, 2014-005567-33, MEIN/14/FEB-PWV/001

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Febuxostat 80/120 mg film coated tablets.The initial daily dose is 80 mg given orally. In case a patient has serum urate level 6 mg/dl after 2 weeks of treatment the dose will be escalated to 120 mg and if tolerated will be maintained during the study treatment period. To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg quaque die (QD ) or in case of colchicine intolerance, Naproxen 550 mg bis in die (BID) with Omeprazole (20-40 mg once daily), if indicated to be used.
febuxostat 80/120mg/day
Starting dose and dose regimen of Febuxostat : the initial daily dose is 80 mg. In case the patient has the serum urate concentration > 6 mg/dl after 2 weeks of treatment the dose will be escalated to 120 mg and if tolerated will be maintained for the duration of the study.
colchicine
Colchicine 0.5 mg tablets.To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg QD
naproxen
Naproxen sodium 550 mg film coated tablets. In case of colchicine intolerance patients will be treated for at least 6 months with Naproxen 550 mg BID and Omeprazole (20-40 mg once daily), if indicated to be used.
omeprazole
Omeprazole 20 mg capsules
(Active Comparator)
Allopurinol 100/300 mg tablets.The initial daily allopurinol dose is 100 mg given orally, to be escalated of 100 mg every 2 weeks in patients with serum urate concentration >6 mg/dl. The maximum dose of allopurinol achievable in the study will depend on kidney function and tolerability, but will not exceed 600 mg daily.To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg QD or in case of colchicine intolerance, Naproxen 550 mg BID with Omeprazole (20-40 mg once daily), if indicated to be used.
allopurinol 100 up to 600mg/day
Starting dose and dose regimen of allopurinol : the initial daily allopurinol dose is 100 mg, to be increased by 100 mg every 2 weeks in patients with serum urate concentration >6 mg/dl. The maximum daily dose of allopurinol achievable in the study will depend on kidney function and tolerability, but will not exceed 600 mg.
colchicine
Colchicine 0.5 mg tablets.To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg QD
naproxen
Naproxen sodium 550 mg film coated tablets. In case of colchicine intolerance patients will be treated for at least 6 months with Naproxen 550 mg BID and Omeprazole (20-40 mg once daily), if indicated to be used.
omeprazole
Omeprazole 20 mg capsules

Primary Outcomes

Measure
Pulse Wave Velocity
time frame: 36 weeks of treatment

Secondary Outcomes

Measure
Changes in Brain natriuretic peptide (BNP) and NTproBNP values
time frame: 12, 24 and 36 weeks of treatment
Changes in inflammation markers
time frame: 12, 24 and 36 weeks of treatment
Changes in oxidative stress parameters
time frame: 12,24 and 36 weeks of treatment
Changes in lipid profile
time frame: 12,24 and 36 weeks of treatment
Percentage of gout patients with a serum Urate acid (sUA) concentration of less than 6 mg/dl
time frame: 12,24 and 36 weeks of treatment
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
time frame: 36 weeks
Changes in Estimated Glomerular Filtration Rate (eGFR) with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
time frame: 12,24 and 36 weeks of treatment
Changes in urine albumin excretion as evaluated by first morning urine albumin/creatinine ratio (mg/g)
time frame: 12,24 and 36 weeks of treatment
Percentage of patients above the sUA target levels
time frame: 12,24 and 36 weeks of treatment after having reached the sUA target levels at week 2
Tender and swollen joint count
time frame: 12,24 and 36 weeks of treatment
Pulse Wave Analysis
time frame: 12,24 and 36 weeks of treatment
Changes in endothelial activation/adhesion markers
time frame: 12,24 and 36 weeks of treatment
Number of participants with adverse events as a measure of Safety and Tolerability
time frame: 36 weeks of treatment

Eligibility Criteria

Male or female participants at least 18 years old.

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 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. 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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Menarini International Operations Luxembourg SA.