Evaluation of Allopurinol, Benzbromarone, and Febuxostat Hemihydrate in Gout Remission: A Randomized Superiority Trial on Urate Lowering Therapy Strategies

The primary objective of the GO TEST FINALE study is to evaluate the difference between two treatment strategies in the proportion of participants with **gout** who meet adapted preliminary remission criteria. These criteria include the absence of tophi, no flares, a Numerical Rating Scale (NRS) pain score due to gout of less than 2, and a disease activity score of less than 2, independent of serum uric acid (sUA) levels, during the last six months of a 24-month follow-up period. This assessment is clinically relevant as it aims to determine the optimal management strategy for maintaining remission in patients with gout, potentially impacting long-term patient outcomes and quality of life. Additionally, the study aims to assess the incremental cost-effectiveness in euros per Quality-Adjusted Life Year (QALY) gained for a treat-to-target (T2T) strategy compared to a treat-to-symptom (T2S) strategy, providing valuable economic insights into the management of gout.

The clinical trial focuses on participants diagnosed with **gout**, a condition characterized by recurrent attacks of inflammatory arthritis. The study population includes both male and female subjects aged 18 years and older, who are mentally competent. Participants are required to have achieved remission for at least 12 months based on adapted preliminary gout remission criteria, which include being free of flares and clinically apparent tophi, maintaining a serum urate level of ≤0.36 mmol/l, and reporting pain due to gout and disease activity at a level of less than 2 on a 10-point Likert-type scale. The trial does not involve a vulnerable population. The total number of participants is not provided, as the sponsor has not disclosed this information. Participants were selected based on their clinical diagnosis of gout or fulfillment of the 2015 ACR-EULAR gout criteria, and they must have been using urate-lowering therapy (ULT) such as allopurinol, benzbromarone, and/or febuxostat. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the efficacy of urate-lowering therapies in patients with **gout** in remission. The trial aims to compare the continuation versus cessation of these therapies over a 24-month period. Participants will be randomly assigned to either continue their current urate-lowering treatment, which may include **allopurinol**, **benzbromarone**, or **febuxostat hemihydrate**, or to cease treatment. The primary objective is to assess the difference in the proportion of participants meeting the adapted preliminary gout remission criteria during the last six months of the follow-up period. Secondary objectives include evaluating the cost-effectiveness of the treatment strategies.

The trial will commence with an inclusion visit, where participants will be screened based on specific criteria, including a clinical diagnosis of gout, use of urate-lowering therapy, and achievement of remission for at least 12 months. Participants must be 18 years or older and provide informed consent. Following the inclusion visit, participants will undergo regular follow-up visits at intervals throughout the 24-month period. These visits will involve clinical assessments and blood tests to monitor serum urate levels and disease activity. Digital questionnaires will be administered every three months, and participants will record any gout flares monthly.

The expected duration of participant involvement is 24 months, with the trial estimated to conclude by June 2025. Conditions that may lead to early termination from the study include withdrawal of consent, non-compliance with study procedures, or adverse events that compromise participant safety. The end-of-study visit will involve a final assessment to evaluate the primary and secondary endpoints. The trial's design ensures that the burden on participants is minimized, aligning with standard care practices, while addressing the global uncertainty regarding optimal treatment strategies for gout.

The clinical trial involves the administration of three **urate lowering therapies** for the treatment of gout in remission. The first experimental medication is **Allopurinol**, a chemical substance with the ATC code M04AA01. It is administered in an oral pharmaceutical form, identified as PHF00005MIG. The maximum daily dosage of Allopurinol is 900 mg, and it is administered orally. The treatment period for Allopurinol is up to 24 months. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

The second experimental medication is **Benzbromarone**, classified under the ATC code M04AB03. This medication is also administered orally, with a pharmaceutical form designated as PHF00009MIG. The maximum daily dose for Benzbromarone is 300 mg, and the treatment duration is set for a maximum of 24 months. Participant compliance is closely monitored to maintain the integrity of the dosing schedule.

The third experimental medication is **Febuxostat Hemihydrate**, with the ATC code M04AA03. It is provided in an oral pharmaceutical form, identified as PHF00082MIG. The maximum daily dosage for Febuxostat Hemihydrate is 120 mg, administered orally, with a treatment period extending up to 24 months. Adherence to the dosing schedule is ensured through regular compliance checks.

All three medications are part of the urate lowering therapy regimen being evaluated in this trial. The trial does not include any non-experimental treatments such as placebo or comparator treatments. The focus is on assessing the efficacy and safety of these medications in maintaining gout remission over the specified treatment period.

Efficacy in the clinical trial titled "GOut TrEatment STrategy (GO TEST) FINALE study" will be assessed by evaluating the difference in the proportion of participants meeting the adapted preliminary gout remission criteria. These criteria include the absence of tophi, no flares, a Numerical Rating Scale (NRS) pain score due to gout of less than 2, and a disease activity score of less than 2, independent of serum urate (sUA) levels. The primary endpoint is the between-group difference in the proportion of patients fulfilling these criteria during the last six months of the 24-month follow-up period. Superiority testing will be conducted, and if superiority is not demonstrated, non-inferiority testing with a prespecified non-inferiority margin of 0.08 will be performed as an exploratory secondary outcome.

The trial will involve the use of urate-lowering therapies, including **allopurinol**, benzbromarone, and febuxostat, administered orally. The maximum treatment period for each medication is 24 months. Participants will be monitored through digital questionnaires every three months, and flares will be recorded monthly. Blood samples will be collected 3-4 times over the 24-month period, depending on the treatment arm. The study aims to provide insights into the optimal treatment strategy for patients with gout in remission, addressing the current uncertainty and potentially reducing health costs associated with suboptimal treatment.