BACKGROUND: Gout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Māori men, 22.9% of Pacific men and 7.4% of New Zealand European men. Effective long-term treatment requires lowering serum urate to <0.36 mmol/L. Allopurinol is the most commonly used urate-lowering medication worldwide. Despite its efficacy and safety, the allopurinol dose escalation treat-to-target serum urate strategy is difficult to implement and there are important inequities in allopurinol prescribing in Aotearoa. The escalation strategy is labour intensive, time consuming and costly for people with gout and the healthcare system. An easy and effective way to dose-escalate allopurinol is required, especially as gout disproportionately affects working-age Māori men and Pacific men, who frequently do not receive optimal care.
METHODS: A 12-month non-inferiority randomised controlled trial in people with gout who have a serum urate ≥ 0.36 mmol/l will be undertaken. 380 participants recruited from primary and secondary care will be randomised to one of the two allopurinol dosing strategies: intensive nurse-led treat-to-target serum urate dosing (intensive treat-to-target) or protocol-driven dose escalation based on dose predicted by an allopurinol dosing model (Easy-Allo). The primary endpoint will be the proportion of participants who achieve target serum urate (<0.36 mmol/L) at 12 months.
BACKGROUND: The New Zealand Northern B Health and Disability Ethics Committee approved the study (2022 FULL 13478). Results will be disseminated in peer-reviewed journals and to participants.
BACKGROUND: ACTRN12622001279718p.

BACKGROUND: Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome (ALL-VASCOR) study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk excluding ischaemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of mortality.
METHODS: The ALL-VASCOR study is a randomised, double-blind, placebo-controlled, multicentre trial that examines the effect of allopurinol therapy (200-500 mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1116 patients aged 40-70 with serum uric acid levels above 5 mg/dL at high and very high risk of cardiovascular disease. The ALL-VASCOR study will also assess the occurrence of long-COVID-19 syndrome. The study will measure primary and secondary as well as additional endpoints and the planned intervention will end on 31 July 2028 unless advised otherwise by the Safe Monitoring Board or other applicable authorities. Participant recruitment is planned to begin in March 2024 in Poland.
BACKGROUND: The study was ethically approved by the Bioethics Committee of Poznan University of Medical Sciences (No 03/23, 12 January 2023). The results are expected after 2028 and will be disseminated in peer-reviewed journals and at international conferences.
UNASSIGNED: 01-15 November 2022.
BACKGROUND: EudraCT: 2022-003573-32, 27 October 2022, ClinicalTrials: NCT05943821, 13 July 2023.

BACKGROUND: Data about the safety of allopurinol in pregnant women are sparsely reported.
OBJECTIVE: To investigate the risk of adverse pregnancy outcome and congenital abnormalities after in utero exposure to allopurinol in inflammatory bowel disease (IBD) pregnancies and in general.
METHODS: We collected safety data of patients with IBD who were treated with allopurinol during pregnancy between January 2013 and March 2022. Additionally, we performed a systematic review about the teratogenic potential of allopurinol.
RESULTS: We collected data from 42 allopurinol-exposed pregnancies, including one twin pregnancy; in all women, allopurinol was combined with a thiopurine. Six pregnancies (14.3%) resulted in miscarriage and one in stillbirth at 32 weeks. A congenital anomaly was observed in one newborn (coarctation of the aorta discovered postpartum). Three pregnancies, including the twin pregnancy, ended in moderate preterm delivery and one in very preterm delivery. Five neonates (15.2%) were small for gestational age. From our literature search, we identified an additional 102 allopurinol-exposed pregnancies resulting in 129 live births, including 36 infants from our cohort. Ten infants (7.8%) were born with a congenital anomaly. Two (1.6%) had a comparable pattern of multiple anomalies. The systematic review sub-analysis including only infants born to mothers with IBD (n = 76) revealed that 2.6% of infants had congenital anomalies after in utero exposure to a low dose of allopurinol.
CONCLUSIONS: Overall, the teratogenicity of allopurinol remains inconclusive. Children conceived by mothers treated for IBD with allopurinol/thiopurine co-therapy do not seem to have an increased risk of congenital anomalies.

Cohort studies have identified several genetic determinants that could predict the clinical response to allopurinol. However, they have not been commonly used for genome-wide investigations to identify genetic determinants on allopurinol metabolism and concentrations. We conducted a genome-wide association study of a prior cross-sectional investigation of patients from the Montreal Heart Institute Biobank undergoing allopurinol therapy. Four endpoints were investigated, namely plasma concentrations of oxypurinol, the active metabolite of allopurinol, allopurinol, and allopurinol-riboside, as well as allopurinol daily dosing. A total of 439 participants (mean age 69.4 years; 86.4% male) taking allopurinol (mean daily dose 194.5 mg) and who had quantifiable oxypurinol concentrations were included in the genome-wide analyses. Participants presented with multiple comorbidities and received concomitant cardiovascular medications. No association achieved the predefined genome-wide threshold values for any of the endpoints (all p > 5 × 10-8). Our results are consistent with prior findings regarding the difficulty in identifying genetic determinants of drug concentrations or pharmacokinetics of allopurinol and its metabolites, as well as allopurinol daily dosing. Given the size of this genome-wide study, collaborative investigations involving larger and diverse cohorts may be required to further identify pharmacogenomic determinants of allopurinol and measure their clinical relevance to personalize allopurinol therapy.

OBJECTIVE: We conducted a prespecified examination of the efficacy and safety of allopurinol and febuxostat administered using a treat-to-target strategy in trial participants with chronic kidney disease (CKD).
METHODS: Prespecified sub cohort analysis of a randomized controlled trial.
METHODS: & Participants: A sub study of the STOP Gout trial in participants with CKD. CKD was defined as an eGFR 30-59 mL/min/1.73 m2 at baseline.
METHODS: Trial participants with CKD and gout and serum urate (sUA) concentration ≥6.8 mg/dL were randomized 1:1 to receive allopurinol or febuxostat. Urate lowering therapy (ULT) was titrated during weeks 0-24 to achieve a goal sUA of <6.0 mg/dl (<5.0 mg/dl with tophi) (Phase 1) and maintained during weeks 25-48 (Phase 2). Gout flare was assessed between weeks 49-72 (Phase 3).
RESULTS: Gout flare between weeks 49-72 (Phase 3) was the primary outcome. Secondary outcomes included sUA goal achievement and ULT dosing at end of Phase 2, and serious adverse events (SAEs).
METHODS: Outcomes between treatment groups were compared using logistic regression models for binary outcomes, and Poisson regression for flare rates. Multivariable models were subsequently used, adjusting for factors identified to be imbalanced by treatment arm.
RESULTS: 351 of 940 participants (37.3%) had CKD; 277 were assessed for the primary outcome. Fewer patients randomized to allopurinol had a flare during phase 3 (32% vs 45%; p=0.02) despite similar attainment of sUA goal (79% vs. 81%; p=0.6) by the end of Phase 2. Acute kidney injury (AKI) was more common in participants with stage 3 CKD randomized to allopurinol compared to febuxostat.
CONCLUSIONS: Limited power to assess infrequent safety events, largely male, older population.
CONCLUSIONS: Allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen.

Taste sensors with an allostery approach have been studied to detect non-charged bitter substances, such as xanthine derivatives, used in foods (e.g., caffeine) or pharmaceuticals (e.g., etofylline). In this study, the authors modified a taste sensor with 3-bromo-2,6-dihydroxybenzoic acid and used it in conjunction with sensory tests to assess the bitterness of non-charged pharmaceuticals with xanthine scaffolds (i.e., acefylline and doxofylline), as well as allopurinol, an analogue of hypoxanthine. The results show that the sensor was able to differentiate between different levels of sample bitterness. For instance, when assessing a 30 mM sample solution, the sensor response to acefylline was 34.24 mV, which corresponded to the highest level of bitterness (τ = 3.50), while the response to allopurinol was lowest at 2.72 mV, corresponding to relatively weaker bitterness (τ = 0.50). Additionally, this study extended the application of the sensor to detect pentoxifylline, an active pharmaceutical ingredient in pediatric medicines. These results underscore the taste sensor\'s value as an additional tool for early-stage assessment and prediction of bitterness in non-charged pharmaceuticals.

BACKGROUND: The generation of reactive oxygen species, which is induced by the activation of the xanthine oxidase (XO) enzymatic system, is one of the primary causes of ischemia-reperfusion injury for an ischemic heart. Allopurinol, as an XO inhibitor, plays an inhibitory role in free radical production in ST-elevation myocardial infarction (STEMI) patients. The aim of this study is to evaluate the impact of allopurinol pre-treatment on post-revascularization outcomes in patients admitted with STEMI.
METHODS: Ninety patients with acute STEMI were enrolled in this randomized double-blind clinical trial and divided into two equal groups. The allopurinol group received a 600 mg allopurinol loading dose before the emergency PCI, and the control group received a placebo medication of the same shape. Thrombolysis in Myocardial Infarction (TIMI) flow, ECG changes, troponin level, and the occurrence of major cardiac events (MACE) during a 1-month follow-up were assessed.
RESULTS: In the end, 81 patients were analyzed. The mean age of the patients was 59.52(11.31) and 61.3(9.25) in the allopurinol and control groups, respectively (p = 0.49). The troponin level 48 hours after the PCI and ST-elevation regression showed no significant difference between the groups [(p = 0.25) and (p = 0.21), respectively]. TIMI flow had improved in the allopurinol group compared to the placebo (p = 0.02). The PCI success rate was 78.6% and 61.5% in the case and control groups, respectively (p = 0.09). MACE and other clinical outcomes were similar between the groups (p > 0.05).
CONCLUSIONS: This study revealed that allopurinol pre-treatment could improve TIMI flow in patients undergoing primary or rescue PCI in an acute STEMI setting.

BACKGROUND: The use of allopurinol has shown promising outcomes in reducing oxidative processes responsible for atherogenic-related cardiovascular events. The current study aims to assess the effects of high-dose allopurinol on the post-revascularization coronary blood flow and inflammatory biomarkers in patients with non-ST segment elevated myocardial infarction (NSTEMI).
METHODS: Eighty NSTEMI patients were randomly divided into two groups: the intervention group (n=40), medicated with a high loading dose of 600 mg allopurinol before the coronary angiography, and the control group (n=40), treated with a placebo. The highly sensitive C-reactive protein (hs-CRP) was measured at baseline and within 24 hours after the cardiac interventions and compared between the case and control groups. Post percutaneous coronary intervention (PCI) Thrombolysis in Myocardial Infarction (TIMI) flow grading was also evaluated as a revascularization endpoint.
RESULTS: The two groups of the study were similar in terms of demographic, clinical, laboratory, and angiographic characteristics (P-value>0.050). The assessed TIMI flow was similar between the cases and the controls both prior to (P-value=0.141) and after (P-value=0.395) the coronary angioplasty. The hs-CRP (P-value=0.016) was significantly higher in the control group. Post-angiographic assessment of hs-CRP revealed an insignificant difference between the groups (P-value=0.104).
CONCLUSIONS: In conclusion, premedication with a high dose of allopurinol in NSTEMI patients did not affect the inflammatory biomarker or the revascularization endpoint.

OBJECTIVE: To compare the risk of urolithiasis in gout patients initiating allopurinol, a xanthine oxidase inhibitor, vs benzbromarone, a uricosuric.
METHODS: Using the 2011-2020 Korea National Health Insurance Service database, we conducted a cohort study on gout patients initiating allopurinol vs benzbromarone as the 1st-line urate-lowering treatment (ULT). The primary outcome was a new onset urinary stone. The secondary outcome was a stone requiring intervention. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazard models with a 5:1 ratio propensity-score matching on > 80 variables. Subgroup analyses were done by age, sex, thiazide use, and cardiovascular (CV) risk.
RESULTS: 61 300 allopurinol initiators PS-matched on 12 260 benzbromarone initiators were included (mean age 59 years, 79% male). During a mean follow-up of 322 days, 619 urolithiasis cases occurred with an incidence rate of 0.87 per 100 person-years in allopurinol and 1.39 in benzbromarone initiators, showing a HR of 0.64 (95% CI, 0.51-0.80). ∼44% of urinary stones required intervention with a HR of 0.61 (95% CI 0.43-0.88). The lower risk associated with allopurinol compared with benzbromarone persisted across subgroups but was greater in the high than non-high CV risk subgroup (p for interaction = 0.02).
CONCLUSIONS: This population-based cohort study found that allopurinol compared with benzbromarone was associated with a substantially lower risk of urolithiasis particularly in the presence of the high CV risk. This finding provides important safety information for clinicians\' decision-making on ULTs of different mechanisms of action.

OBJECTIVE: Currently, gout management, particularly urate-lowering therapy (ULT), is often suboptimal. Nurses successfully manage various diseases including gout. As gout prevalence is rising, and rheumatologists and general practitioners face shortages, a new approach is imperative. This real-life prospective cohort study evaluated the effectiveness of nurse-led care employing a treat-to-target strategy for gout management over a 2-year period.
METHODS: All consecutively confirmed gout patients were included. The nurse-led clinic provided a structured treatment plan with consultations, patient leaflets, telephone contacts and laboratory monitoring. After a year of nurse-led care, patients transitioned to continued care in general practice. Follow-up data were complete through registries. The primary outcome was achieving target p-urate levels (<0.36 mmol/L) at 2 years after diagnosis. Secondary outcomes included treatment continuation and achievement of target p-urate levels in specific subgroups. The results were compared with patients diagnosed in the same clinic but followed up in \'usual care\'.
RESULTS: In the nurse-led group (n=114), 83% achieved target p-urate levels and ULT was continued by 98%. This trend persisted across various patient subgroups. Only 44% of patients in usual care achieved target p-urate and with insufficient doses of allopurinol . Nurse-led care involved an average of two visits and three telephone contacts over 336 days. The 2-year mortality rate was 15%.
CONCLUSIONS: Nurse-led gout care, employing a targeted approach, was associated with a very high uptake of and adherence to ULT. The encouraging results were not achieved in usual care although a direct comparison might be influenced by selection bias.