Gout Hyperuricaemia
Conditions
Interventions
Patients who are eligible for participation and have signed informed consent
are randomised to either febuxostat or allopurinol treatment. The initial daily
dose for febuxostat starts with 80 mg. In
Arterial stiffness
Cardiovascular risks
Gout
Urate Lowering Therapy
Sponsors
Menarini International Operations Luxembourg S.A.
Eligibility
Age
18 Years to 64 Years
Inclusion 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. At least six out of twelve clinical, laboratory and X-ray phenomena listed below are present: 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 levels >8 mg/dl;;6) Overall CV risk factors based on the scoring proposed by the Joint Task Force of the European Society of Cardiology and other Societies on cardiovascular disease prevention in clinical practice between 5-15% (inclusive), as per protocol appendix 2. Patient with diabetes mellitus type 2 could be included in the study if their CV risk factor is calculated as *7%;;7) Concomitant medications should be maintained stable during the last 2 weeks before randomisation.
Exclusion criteria
Exclusion criteria: 1) Severe chronic renal failure (creatinine clearance 2 times the upper limit of normal;;4) Diabetes mellitus type1; ;5) Life-threatening co-morbidity or 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, benzobromarone, pyrazinamide, captopril and enalapril (for Allopurinol), tegafur, pegloticase and tacrolimus;;13) Hypersensitivity to any 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 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, 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, impantable); * 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. In each case of delayed menstrual period (over one month between menstruations) absence of pregnancy has to be confirmed. This also applies to WOCBP with infrequent or irregular menstrual cycles.;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 limiting to ability to obtain adequate PWV/PWA recordings. Special attention should be paid to any physical abnormalities which could affect quality of PWV/PWA measurement: * neck region- flexibility of the neck and accessibility of carotid artery; <br
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the effects of febuxostat and allopurinol on Pulse Wave Velocity (PWV) after 36 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints include: 1) Changes in BNP and NTproBNP values after 12, 24 and 36 weeks of treatment; 2) Changes in inflammation markers (hsCRP, TNF-*, sUA, and plasma fibrinogen) after 12, 24 and 36 weeks of treatment; 3) Changes in oxidative stress parameters [Malondialdehyde (MDA), Myeloperoxidase (MPO) Oxidized low-density lipoprotein (Ox-LDL), Paraoxonase 1 and 2 (PON1, PON2)] after 12, 24 and 36 weeks of treatment; 4) Changes in lipid profile after 12, 24 and 36 weeks of treatment; 5) Percentage of gout patients with a serum urate concentration of less than, or equal to 6 mg/dl after 12, 24 and 36 weeks of treatment. 6) 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, 10.4-11.0 mg/dl, >11 mg/dl; 7) Changes in eGFR with CKD-EPI formula after 12, 24 and 36 weeks of treatment; 8) Changes in urine albumin excretion as evaluated by first morning urine albumin/creatinine ratio (mg/g) after 12, 24 and 36 weeks of treatment; 9) Percentage of patients above the sUA target levels at Week 12, Week 24 and week 36 after having reached the sUA target levels at Week 2; 10) Tender and swollen joint count; 11) Pulse Wave Analysis (including modifications of PWV, arterial stiffness, central blood pressure and augmentation index) after , 12, 24 and 36 weeks of treatment ; 12) Changes in endothelial activation/adhesion markers (sVCAM, sICAM, vWF, e-selectine) after 12, 24 and 36 weeks of treatment (These parameters will be evaluated in a subset of patients enrolled in selected centres only) 13) Safety and tolerability will be assessed by the following parameters evaluated at Screening and at week 2 , 12 , 24 and 36: * Overall incidence of adverse events (AEs). * Evidence from physical examination * Vital signs (systolic/diastolic blood pressure, pulse, body weight, axillary body temperature). * Laboratory parameters (blood chemistry, haematology and u | — |
Countries
Croatia, Germany, Italy, Netherlands, Poland, Romania, Serbia
Outcome results
None listed