Intensive Urate Lowering Therapy of Febuxostat Compared to Allopurinol on Cardiovascular Risk in Patients With Gout

Summary

There is a mounting and clear association between hyperuricaemia, gout and the presence of traditional cardiovascular (CV) risk factors and CV event-equivalent conditions such as chronic kidney disease, metabolic syndrome, and diabetes. Gout is associated with increased risk of CV events such as myocardial infarction and CV death. Furthermore hyperuricaemia is clearly associated with an increased arterial stiffness, a marker of pre-clinical atherosclerosis. Carotid-femoral pulse wave velocity (PWV) is the "gold standard" measurement of arterial stiffness and it is considered, in this trial, as a valid surrogate endpoint with clearly established relevance to predict cardiovascular disease (CVD) clinical outcome In this randomised trial conducted on adult subjects with a history of gout, we use surrogate endpoints to investigate the efficacy of febuxostat compared with allopurinol to predict (CVD) clinical outcome.

Eligible subjects were randomised in a 1:1 ratio to the following treatment groups:

* Test product: febuxostat 80 mg or 120 mg once daily (120 mg daily, if serum urate was \>6 mg/dL after 2 weeks of treatment at 80 mg daily).
* Active comparator: allopurinol 100 mg once daily (up to a maximum dose of 600 mg daily escalated in 100 mg increments every 2 weeks, if serum urate acid (sUA) was \>6 mg/dL after 2 weeks of treatment at the previous dose).

The study duration was 39 weeks, which included the:

* Run-in/screening period: 1 week (extendable up to a maximum of 30 days according to variability of sUA levels);
* Treatment period: 36 weeks;
* Safety follow-up period: 2 weeks.

Conditions

• Gout

Interventions

DRUG

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.

DRUG

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.

DRUG

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

DRUG

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.

DRUG

Omeprazole

Omeprazole 20 mg capsules, co-administered to patients for gastric protection.

Sponsors & Collaborators

• Menarini International Operations Luxembourg SA

  lead INDUSTRY

Principal Investigators

• Claudio Borghi, Prof · Policlinico S.Orsola - Malpighi Medicina Interna Borghi

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-08-17

Primary Completion

2017-05-10

Completion

2017-05-10

Countries

• Germany
• Italy
• Netherlands
• Poland
• Romania
• Serbia

Study Locations