A pragmatic randomised trial comparing Oral Corticosteroids and Colchicine for the treatment of goUt flaRes in people with relative contraindications to non-steroidal anti-inflammatory drugs (the OCCUR trial)

Research question: What is the clinical and cost-effectiveness of oral prednisolone versus colchicine in people currently experiencing a gout flare who have relative contraindications to non-steroidal anti-inflammatory drugs (NSAIDs)?

Background: Gout is the most prevalent inflammatory arthritis, affecting 2.5% of adults in the UK, and causes significant pain, disability and impaired health-related quality of life. It is largely managed in primary care, where gout flares are most frequently treated with NSAIDs. However, relative contraindications to NSAIDs such as older age, chronic kidney disease or cardiovascular disease are prevalent in people with gout.

When gout flares occur in people with such contraindications, alternative treatments to NSAIDs, such as colchicine and corticosteroids, are needed. Objectives: to compare:

(1) the effectiveness of oral prednisolone and colchicine at reducing pain in adults with a gout flare and relative contraindications to NSAIDs;

(2) the effect of oral prednisolone and colchicine on time to resolution of pain, joint swelling and tenderness, adverse effects, physical function, quality of life, participant global assessment of treatment response, flare relapse/recurrence; sleep, use of walking aids, work/education absence, adherence and treatment satisfaction; and

(3) the cost-effectiveness of oral prednisolone and colchicine.

Methods: A multicentre pragmatic randomised open-label two-arm parallel group superiority trial with 12-month internal pilot and health economic evaluation. 280 adults aged =18-years with relative contraindications to NSAIDs and currently experiencing a gout flare will be recruited from up to 100 general practices across the UK. Participants will be randomised individually in a 1:1 ratio to oral prednisolone 30mg daily or colchicine 0.5mg three times daily (0.5mg twice daily if aged >70-years or known estimated glomerular filtration rate <30) via a secure centralised web-based, automated computer-generated randomisation system.

The primary outcome (change in pain intensity from baseline over days 1-7) will be collected twice daily during week 1 and then also weekly at weeks 2, 3 and 4, along with the secondary outcomes . Key secondary outcomes will include time to resolution of joint pain, swelling and tenderness, adverse effects (including gastrointestinal symptoms), physical function, quality of life, and cost, including healthcare utilisation. Outcomes will be collected by text-message or paper diary according to participant preference.

Timelines for delivery: 40 months. Months 0-9: set-up, 10-22: internal pilot phase, 10-33: participant screening & recruitment, 34: complete follow-up. 35-40: data analyses, write up and dissemination.

Anticipated impact and dissemination: New evidence will be provided about the relative effectiveness and safety of oral prednisolone and colchicine for gout flares in people who have relative contraindications to NSAIDs, which will inform treatment decisions. If cost-effective, these simple interventions will be easily implemented across clinical services.

As well as publishing in high impact journals and presenting at scientific meetings, we will work closely with our networks, professional bodies, specialist societies, charities, and the National Institute for Health and Care Excellence (NICE) to ensure wide dissemination and uptake, supported by our PPIE group and Keele’s Impact Accelerator Unit.