About the Trial
The T2T study is a multi-centre pragmatic RCT with an internal pilot and long term follow up.
Gout affects 1 in 40 adults in the UK. It is caused by high urate level which deposits as urate crystals inside the joints. When shed into the joint cavity, they cause gout attacks which manifests as severe joint pain, swelling, inability to use the joint and lasts for 1-2 weeks. Over time, the attacks become frequent and joint damage may occur. Medicines that lower urate level and dissolve these crystals are cheap, safe, and have been available for decades. However, whether their use at doses high enough to dissolve urate crystals prevents gout attacks is unknown. There is an absence of direct randomised controlled trial data that such goal driven urate lowering treatment (ULT), with target serum urate <360μmol/L prevents gout attacks in a cost-effective manner compared to treating when symptoms worsen. This lack of evidence results in poor gout management and culminated in discordant recommendations from gout treatment guidelines.
The objectives of this study are to evaluate the effects of allopurinol-based treat-to-target ULT on the number of gout attacks (primary outcome), gout flare severity, serum urate, quality of life, renal function and adverse events. We will also examine the cost-effectiveness, acceptability and adherence with such treatment.
Recruitment target: 466 patients with recurrent gout attacks.
Approximate number of sites required: 60 GP Practices.
Study population: Patients aged 18 years or over, who are registered at a participating GP practice.
Planned recruitment period: Internal pilot will be 4 months and the main trial will be 7 months.
Planned start date: Closed to recruitment.
Follow up: 4 years
Internal pilot:
Objectives: To assess consent rate, attrition, quality of outcome data, delivery of treat-to-target urate-lowering treatment (ULT) and preliminary estimate of the effect or efficacy of the intervention.
Full trial:
Primary objective: To evaluate the effectiveness of allopurinol-based treat-to-target ULT versus usual general practitioner (GP) care on number of gout flares over two years.
Methods
Study design: Multi-centre pragmatic RCT with internal pilot and long term follow-up
Setting: Primary care
Study duration: 80 months
Participants: People with recurrent gout attacks(at least 1 attack in previous 12 months), older than 18 years
Study groups:
Group A - allopurinol-based treat-to-target ULT
Group B - usual GP care
Intervention delivery: General Practice Nurses
Randomisation: 1:1 individual randomisation stratified by region and prior intolerance to Colchicine
Study participation: Each participant in the study for 4 years, 2 years each in the RCT and long-term extension respectively
Inclusion Criteria
- Aged 18 years or over
- Ability to give informed consent
- Meets the clinical American College of Rheumatology/European League Against Rheumatism classification criteria for gout
- 1 or more flares of gout in the previous 12 months
- Serum urate 360 or over, 360 or more μmol/l regardless of current ULT
Exclusion Criteria
- Previous side-effects to allopurinol that contraindicate rechallenge
- Dementia, severe psychological disturbance i.e. mental health illness that makes receiving the study information and initial screening questionnaire from GP a stressful experience
- Unable to comply with study procedures
- Life expectancy less than 12 months
- Cancer treatment i.e. surgery, radiotherapy, or chemotherapy in the previous 12 months
- Solid-organ transplant
- Cirrhosis of the liver
- Autoimmune rheumatic disease
- Inflammatory bowel disease
- Current long-term daily prednisolone defined as continuous use for ≥ 30 days or current other immunosuppressive treatments
- Stage 4/5 chronic kidney disease (CKD)
- Pregnant, breastfeeding or planning to become pregnant
This study has now closed to recruitment.