HLA-B*58:01-Guided Therapy for Gout: Effectiveness, Safety, and Cost-Effectiveness

NCT07369622 | Not Yet Recruiting Phase 4

• 2 other identifiers: HLA-GOUT-SCARS-2026HPMU-HLA-GOUT
• Study Type: interventional
• Target: 228
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Gout Initiating Urate-loweringUrate-lowering Therapy; Gout Arthritis; Gout and Hyperuricemia

Keywords

HLA-B*58:01; HLA genotyping; Pharmacogenomics; Allopurinol; febuxostat; Pharmacogenetic screening; Severe cutaneous adverse reactions (SCARs); Stevens-Johnson syndrome (SJS); Toxic epidermal necrolysis (TEN); Cost-effectiveness analysis

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Achieving Target Serum Uric Acid <5.0 mg/dL (≈300 µmol/L)

  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.

  At Month 12 after initiation of urate-lowering therapy

Study Arms (3)

HLA-B*58:01 Negative: Allopurinol

ACTIVE COMPARATOR

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).

Diagnostic Test: HLA-B*58:01 Genotyping; Drug: Allopurinol Tablet

HLA-B*58:01 Positive: Febuxostat

ACTIVE COMPARATOR

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.

Diagnostic Test: HLA-B*58:01 Genotyping; Drug: Febuxostat

No HLA-B*58:01 Testing: Febuxostat

ACTIVE COMPARATOR

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).

Drug: Febuxostat

Interventions

HLA-B*58:01 Genotyping DIAGNOSTIC_TEST

Whole-blood sample is collected for HLA-B58:01 genotyping using a PCR-based assay with allele-specific primers. Results are classified as HLA-B58:01 positive or negative and are used to guide urate-lowering therapy selection (allopurinol for negative; febuxostat for positive).

Also known as: HLA-B*5801 test, PCR-based HLA-B*58:01 typing

HLA-B*58:01 Negative: Allopurinol; HLA-B*58:01 Positive: Febuxostat

Allopurinol Tablet DRUG

Oral allopurinol is initiated as urate-lowering therapy in participants who are HLA-B\*58:01 negative. Dosing and titration follow routine clinical practice with consideration of kidney function and serum urate targets. Participants are followed for 12 months with scheduled visits to assess serum urate control, gout flares, and safety outcomes including active surveillance for severe cutaneous adverse reactions (SCARs).

Also known as: Xanthine oxidase inhibitor

HLA-B*58:01 Negative: Allopurinol

Febuxostat DRUG

Oral febuxostat is used as an alternative urate-lowering therapy for participants who are HLA-B\*58:01 positive to avoid allopurinol-associated SCAR risk, and for a comparison cohort treated without HLA testing. Participants are followed for 12 months with scheduled visits to evaluate serum urate response, gout flares, and safety (including SCAR surveillance and routine liver/kidney function monitoring).

Also known as: Xanthine oxidase inhibitor

HLA-B*58:01 Positive: Febuxostat; No HLA-B*58:01 Testing: Febuxostat

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Haiphong University of Medicine and Pharmacy: lead

MeSH Terms

Conditions

Arthritis, Gouty; Gout; Hyperuricemia; Stevens-Johnson Syndrome

Interventions

Allopurinol; Febuxostat

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Stomatitis; Mouth Diseases; Stomatognathic Diseases; Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Erythema Multiforme; Erythema; Skin Diseases, Vesiculobullous; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Ngoc Son Ba Nguyen

CONTACT

+84916088678; son.nguyenba2012@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2026
• First Posted: January 27, 2026
• Study Start: January 20, 2026
• Primary Completion (Estimated): June 20, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 6 months after publication of the primary results and ending 5 years thereafter.
• Access Criteria: De-identified individual participant data (IPD) that underlie the results reported in the primary publication, along with the study protocol (and SAP/analytic code if selected), will be available upon reasonable request. Requests may be submitted by qualified researchers with a methodologically sound proposal to the corresponding author. Proposals will be reviewed by the study team and approved in accordance with institutional policies and applicable regulations. Access will be granted after execution of a data use agreement. Data will be provided in de-identified form; no direct identifiers will be shared and recipients must not attempt re-identification.