Peeters Iris Rose (1,2), Den Broeder Alfons A (1,4), Taylor William J (3), Den Broeder Nathan (1,2), Flendrie Marcel1, Van Herwaarden Noortje (1,5)
Affiliation(s):
1. Department of Rheumatology, Sint Maartenskliniek, Ubbergen, The Netherlands
2. Radboud Institute of Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
3. Department Of Medicine, University of Otago Wellington, Newtown, Wellington, New Zealand
4. Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
5. Department of Pharmacology-Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands
Background: Long-term gout treatment is based on reducing serum urate levels using urate-lowering therapy (ULT). Most guidelines recommend using a lifelong continuation treat-to-target (T2T) strategy, in which ULT is dosed or combined until a serum urate target has been reached and maintained. However, a frequently used alternative strategy in clinical practice is a treat-to-avoid-symptoms (T2S) ULT discontinuation strategy, with the possibility of restarting medication. This latter strategy aims at an acceptable symptom state, regardless of serum urate levels. High-quality evidence to support either strategy for patients in prolonged remission while using ULT is lacking.
Objectives: The primary aim of the Gout TrEatment Strategy (GO TEST) Finale study is to investigate whether a continued ULT T2T strategy is superior to switching to a ULT T2S discontinuation strategy in gout patients currently using ULT and fulfilling preliminary gout remission criteria.
Methods: We developed an investigator-driven pragmatic, open-label, multicenter, randomized, superiority treatment strategy trial (GO TEST Finale). At least 278 gout patients using ULT who are in remission (>12 months, preliminary gout remission criteria) will be randomized 1:1 to a continued T2T strategy (treatment target serum urate < 0.36mmol/l) or switched to a T2S discontinuation strategy in which ULT is tapered to stop and restarted in case of (persistent or recurrent) flaring. The primary outcome is the between-group difference in the proportion of patients not in remission during the last six months of 24 months follow-up and will be analyzed using a two proportion z test. Secondary outcomes are group differences in gout flare incidence, reintroduction or adaptation of ULT, use of anti-inflammatory drugs, serum urate changes, occurrence of adverse events (with special interest in cardiovascular and renal events), and cost-effectiveness. Only when superiority cannot be demonstrated, exploratory non-inferiority testing will be performed of the T2S strategy compared to the T2T strategy by calculating a confidence interval using the Miettinen and Nurminen method, with a pre-defined non-inferiority margin of 8%.
Status: Patient recruitment started in February 2021 and is expected to be complete in spring 2023.
Findings: Currently, 259 patients have been randomized. The mean age is 67 years (SD 10.5) and 93.4% of participants is male. Mean disease duration (from first gout attack) is 10.4 years (SD 8.0) and duration of gout remission is 13-24 months for 30.4% and > 24 months for 69.6% of participants. Mean baseline serum urate is 0.28 mmol/l (SD 0.05) and most participants (90.3%) use allopurinol (5.4% use benzbromarone, 3.5% use febuxostat and 0.4% use allopurinol combined with benzbromaron and 0.4% use benzbromarone combined with febuxostat).
Significance of the project: This study will be the first clinical trial comparing two ULT treatment strategies in patients with gout in remission. It will contribute to more specific and unambiguous guideline recommendations and improved cost-effectiveness of long-term gout treatment. It also paves the way (exploratory) to individualized long-term ULT treatment.
Trial registration: International Clinical Trial Registry Platform (ICTRP): NL9245, registration date 02-02-2021 (METC Oost-Nederland NL74350.091.20), EudraCT: EUCTR2020-005730-15-NL, registration date 11-01-2021.