A Prospective Interventional Study Comparing Genotype-Guided Therapy Versus Usual Care to Prevent Severe Cutaneous Adverse Reactions Associated With Allopurinol and Carbamazepine in Vietnam
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 228
- 主要终点
- Proportion of Participants Achieving Target Serum Uric Acid <5.0 mg/dL (≈300 µmol/L)
研究概览
简要总结
Severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), are rare but life-threatening complications that can occur after starting allopurinol for gout. The HLA-B58:01 allele is a strong genetic risk factor for allopurinol-associated SCARs in Asian populations. This study evaluates the feasibility and clinical value of HLA-B58:01 screening before first-time allopurinol use in Vietnamese adults with gout.
Adults (≥18 years) diagnosed with gout (ACR/EULAR 2020 criteria) and initiating urate-lowering therapy will be enrolled at Hai Phong International General Hospital (January 2025-June 2027). Participants who undergo HLA-B58:01 genotyping (PCR-based assay) will be treated according to test results: HLA-B58:01 negative participants receive allopurinol; HLA-B58:01 positive participants receive febuxostat. A comparison group consists of patients treated with febuxostat without HLA testing. Participants will be followed for 12 months with assessments at baseline, 1, 3, 6, and 12 months to monitor serum uric acid, gout flares, and safety outcomes (SCARs and other adverse events, including liver and kidney function). The study also includes an economic evaluation to estimate the cost-effectiveness of HLA-B58:01 screening for preventing SCARs and optimizing gout treatment.
详细描述
Background and rationale: Allopurinol is a first-line urate-lowering therapy for gout but is a leading cause of severe cutaneous adverse reactions (SCARs), including SJS/TEN and DRESS. These reactions carry substantial morbidity, mortality, and healthcare costs. Genetic susceptibility-particularly carriage of HLA-B*58:01-has been consistently associated with allopurinol-induced SCARs, and pre-treatment HLA screening has reduced SCARs in several Asian settings. However, implementation evidence in Vietnam remains limited. This study is designed to generate local clinical and economic evidence to support an HLA-guided prescribing strategy.
Study objectives:
Describe the prevalence of HLA-B*58:01 among adult Vietnamese patients with gout initiating allopurinol for the first time.
Compare effectiveness and safety outcomes between an HLA-guided strategy (allopurinol for HLA-B58:01 negative; febuxostat for HLA-B58:01 positive) and a non-tested febuxostat strategy.
Evaluate the cost-effectiveness of HLA-B*58:01 screening in preventing SCARs and informing treatment selection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 years.
- •Diagnosis of gout according to the 2020 ACR/EULAR classification criteria.
- •Indicated for initiation of urate-lowering therapy (ULT) and allopurinol-naïve (no prior allopurinol exposure).
- •Able and willing to comply with scheduled follow-up visits (baseline, Months 1, 3, 6, and 12).
- •Provides written informed consent for participation.
- •For the genotyping arms: provides consent for blood sampling and HLA-B*58:01 genotyping.
排除标准
- •Prior use of allopurinol or history of hypersensitivity reaction to allopurinol.
- •Known hypersensitivity to febuxostat (for participants who would receive febuxostat).
- •Current or recent severe skin reaction (suspected/confirmed SCAR) from any cause.
- •End-stage kidney disease requiring dialysis or kidney transplantation.
- •Severe hepatic impairment or active severe liver disease (e.g., AST/ALT >3× ULN at baseline).
- •Severe uncontrolled medical conditions that, in the investigator's judgment, could interfere with treatment or follow-up (e.g., decompensated heart failure, active malignancy requiring intensive treatment).
- •Use of systemic immunosuppressive therapy (e.g., high-dose corticosteroids, biologics, chemotherapy) at enrollment.
- •Pregnancy or breastfeeding.
- •Participation in another interventional clinical study that could affect the outcomes of this study.
- •Inability to provide informed consent or inability to adhere to study procedures.
研究组 & 干预措施
HLA-B*58:01 Negative: Allopurinol
Participants test negative for HLA-B*58:01 and initiate allopurinol as first-line urate-lowering therapy. Follow-up for 12 months with visits at baseline, 1, 3, 6, and 12 months to assess serum urate control, gout flares, and safety (including active surveillance for SCARs and routine liver/kidney function monitoring).
干预措施: HLA-B*58:01 Genotyping (Diagnostic Test)
HLA-B*58:01 Negative: Allopurinol
Participants test negative for HLA-B*58:01 and initiate allopurinol as first-line urate-lowering therapy. Follow-up for 12 months with visits at baseline, 1, 3, 6, and 12 months to assess serum urate control, gout flares, and safety (including active surveillance for SCARs and routine liver/kidney function monitoring).
干预措施: Allopurinol Tablet (Drug)
HLA-B*58:01 Positive: Febuxostat
Participants test positive for HLA-B*58:01 and receive febuxostat as an alternative urate-lowering therapy to avoid allopurinol-associated SCAR risk. Follow-up for 12 months with visits at baseline, 1, 3, 6, and 12 months to evaluate serum urate response, gout flares, and safety outcomes.
干预措施: HLA-B*58:01 Genotyping (Diagnostic Test)
HLA-B*58:01 Positive: Febuxostat
Participants test positive for HLA-B*58:01 and receive febuxostat as an alternative urate-lowering therapy to avoid allopurinol-associated SCAR risk. Follow-up for 12 months with visits at baseline, 1, 3, 6, and 12 months to evaluate serum urate response, gout flares, and safety outcomes.
干预措施: Febuxostat (Drug)
No HLA-B*58:01 Testing: Febuxostat
Participants do not undergo HLA-B*58:01 testing and are treated directly with febuxostat as urate-lowering therapy under routine clinical practice. Follow-up for 12 months with visits at baseline, 1, 3, 6, and 12 months to assess effectiveness (serum urate control, gout flares) and safety (including SCAR surveillance and laboratory monitoring).
干预措施: Febuxostat (Drug)
结局指标
主要结局
Proportion of Participants Achieving Target Serum Uric Acid <5.0 mg/dL (≈300 µmol/L)
时间窗: At Month 12 after initiation of urate-lowering therapy
Serum uric acid is measured by venous blood sampling using an automated biochemistry analyzer at baseline and follow-up visits (1, 3, 6, and 12 months). The primary endpoint is the proportion of participants who achieve the target serum uric acid level \<5.0 mg/dL (approximately \<300 µmol/L) at the 12-month visit.
次要结局
未报告次要终点