Lead Investigator: Michael Wiese, University of South Australia
Title of Proposal Research: Individualisation of gout flare prophylaxis when initiating urate-lowering therapy
Vivli Data Request: 6464
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Gout is the most common form of inflammatory arthritis, affecting approximately 1.6–6.8% of the Australian population. It occurs when the serum urate (SU) concentration in the blood exceeds the level of saturation, causing the urate salts to solidify and form monosodium urate crystals which deposit in the joints and soft tissues of susceptible individuals. The interaction between these crystals and the immune system results in an acute inflammatory response, known as a ‘gout flare’. Although self-limiting, gout flares cause immense pain, have considerable impact on quality of life and can reoccur frequently. Despite the perceived episodic nature of this disease, gout is a chronic condition and if left untreated can result in tophi (chronic collections of inflammatory tissue around the monosodium urate crystals), chronic gouty arthritis, gouty bone erosion and permanent disability. To improve the quality of life for people with gout and with the associated health care costs, hospitalizations and overall economic burden set to rise, it is important to focus on optimising management.
The long-term management of gout involves the use of urate-lowering therapy (ULT) to reduce SU concentrations, thus allowing for crystal dissolution and eventual flare cessation. However, after commencing ULT, some patients may experience a temporary rise in gout flares which may last up to 6-12 months. The inability to predict who will flare when commencing therapy, or when they will flare, has prompted the recommendation that gout flare prophylaxis be considered for a minimum of 6-months in all patients. Despite the common use of prophylaxis in clinical practice, few studies have investigated the efficacy and safety of this approach. Using the diverse range of data commonly collected in clinical trials (e.g. data on patient characteristics, laboratory data, disease classification, pharmacokinetic, concomitant medicines, etc), we hypothesize it will be possible to identify patients likely to experience ULT-induced gout flares. Being able to predict flares will enable clinicians to make more informed decisions regarding whether to give a patient flare prophylaxis and for how long, thereby improving the risk versus benefit ratio for patients and contributing to the quality use of medicines.
This research will be conducted using participant-level data meta-analysis. Available data from gout patients initiating ULT will be analysed to identify and validate predictors of ULT-induced gout flares and investigate the safety and efficacy of gout flare prophylaxis. This will be performed using cox-proportional hazard / time-to-event modelling. This type of modelling allows for multiple covariates to be tested into the model, both individually and simultaneously in order to investigate if they influence the rate of flares.
Requested Studies:
A Multicenter, Randomized, Active-Control, Phase 3B Study to Evaluate the Cardiovascular Safety of Febuxostat and Allopurinol in Subjects With Gout and Cardiovascular Comorbidities
Sponsor: Takeda
Study ID: NCT01101035
Sponsor ID: TMX-67_301
A Phase 3, Randomized, Double Blind, Multicenter, Placebo Controlled Study to Evaluate the Efficacy and Safety of Febuxostat 40 mg XR, 80 mg XR, 40 mg IR and 80 mg IR in Subjects With Gout
Sponsor: Takeda
Study ID: NCT02139046
Sponsor ID: FEB-XR_301
A Phase 2, Randomized, Double Blind, Multicenter, Placebo Controlled Study to Evaluate the Efficacy and Safety of Febuxostat 40 mg XR, 80 mg XR, 40 mg IR and 80 mg IR in Subjects With Gout and Moderate Renal Impairment
Sponsor: Takeda
Study ID: NCT02128490
Sponsor ID: FEB-XR_201
A Multicenter, Randomized, Double-Blind, Phase 2 Study to Evaluate the Effect of Febuxostat Versus Placebo on Renal Function in Gout Subjects With Hyperuricemia and Moderate to Severe Renal Impairment
Sponsor: Takeda
Study ID: NCT01082640
Sponsor ID: TMX-67_203
A Multicenter, Randomized, Double-Blind, Phase 2 Study to Evaluate the Effect of Febuxostat Versus Placebo in Joint Damage in Hyperuricemic Subjects With Early Gout
Sponsor: Takeda
Study ID: NCT01078389
Sponsor ID: TMX-67_204
A Phase 3, Randomized, Multicenter, Double-Blind, Allopurinol-Controlled Study Assessing the Efficacy and Safety of Oral Febuxostat in Subjects With Gout.
Sponsor: Takeda
Study ID: NCT00430248
Sponsor ID: F-GT06-153
A Phase 3, Open-Label, Randomized, Allopurinol-Controlled Study to Assess the Long-Term Safety of Oral Febuxostat in Subjects With Gout
Sponsor: Takeda
Study ID: NCT00175019
Sponsor ID: C02-021
Phase II, Dose-Response, Safety and Efficacy Study of Oral TMX-67 in Subjects With Gout.
Sponsor: Takeda
Study ID: NCT00174967
Sponsor ID: TMX-00-004
Phase II, Open-Label Study, to Assess the Long-Term Safety of Oral TMX-67 in Subjects With Gout
Sponsor: Takeda
Study ID: NCT00174941
Sponsor ID: TMX-01-005
A Phase 3, Randomized, Multicenter, Allopurinol and Placebo-Controlled Study Assessing the Safety and Efficacy of Oral Febuxostat in Subjects With Gout.
Sponsor: Takeda
Study ID: NCT00174915
Sponsor ID: C02-009
A Phase 3, Randomized, Multicenter Study Comparing the Safety and Efficacy of Oral Febuxostat Versus Allopurinol in Subjects With Gout
Sponsor: Takeda
Study ID: NCT00102440
Sponsor ID: C02-010
Update: This data request was withdrawn on 12-May-2023 by the researcher.