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NCT02579096

CSP594 Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat

Completed Phase 4 Results posted Last updated 29 March 2024
What this trial tests

Phase 4 trial testing allopurinol capsule, 100-800 mg by mouth once daily in Gout in 950 participants. Completed in 15 April 2021.

Timeline
6 March 2017
Primary endpoint
1 February 2021
15 April 2021

Quick facts

Lead sponsorVA Office of Research and Development
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment950
Start date6 March 2017
Primary completion1 February 2021
Estimated completion15 April 2021
Sites23 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

VA Office of Research and Development — full company profile →

Who can join

18 and older, any sex, with Gout or Chronic Kidney Diseases. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Experiencing ≥ 1 Gout Flare During Phase 3 Primary · Phase III of the study (weeks 49-72 of study duration)

Participants were defined as flaring in Phase 3 if they: -1) met 3 of 4 following participant-reported criteria: * a) warm joint(s) * b) swollen joint(s) * c) pain (\>3) at rest on a scale of 0-10 (10 being the worst pain) * d) self-identified gout flare OR -2) reported use of medications to treat flare

GroupValue95% CI
Allopurinol / Sham Comparator (Febuxostat)135
Febuxostat / Sham Comparator (Allopurinol)165

Adverse events — posted to ClinicalTrials.gov

Time frame: Beginning at informed consent and continuing until the end of participation in the study at 72 weeks, plus 30 days of observation.. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Allopurinol / Sham Comparator (Febuxostat)
Serious: 125/468 (27%)
Deaths: 8/468
Febuxostat / Sham Comparator (Allopurinol)
Serious: 123/472 (26%)
Deaths: 8/472

Serious adverse events (205 terms)

ReactionSystemAllopurinol / Sham Compara…Febuxostat / Sham Comparat…
Cardiac failureCardiac disorders
Acute kidney injuryRenal and urinary disorders
Arrhythmia supraventricularCardiac disorders
CellulitisInfections and infestations
PneumoniaInfections and infestations
Myocardial infarctionCardiac disorders
Urinary tract infectionInfections and infestations
Cerebrovascular accidentNervous system disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
SepsisInfections and infestations
FallInjury, poisoning and procedural complications
Chest painGeneral disorders
CholecystitisHepatobiliary disorders
HyperglycaemiaMetabolism and nutrition disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Angina unstableCardiac disorders
HyperkalaemiaMetabolism and nutrition disorders
HypoglycaemiaMetabolism and nutrition disorders
Knee arthroplastySurgical and medical procedures
AnaemiaBlood and lymphatic system disorders
BradycardiaCardiac disorders
Coronary artery diseaseCardiac disorders
Gastrointestinal haemorrhageGastrointestinal disorders
DiverticulitisInfections and infestations
Other adverse events (5 terms — click to expand)

ReactionSystemAllopurinol / Sham Compara…Febuxostat / Sham Comparat…
Alanine aminotransferase increasedInvestigations
Drug eruptionSkin and subcutaneous tissue disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Abdominal discomfortGastrointestinal disorders

Most-reported serious reactions: Cardiac failure, Acute kidney injury, Arrhythmia supraventricular, Cellulitis, Pneumonia, Myocardial infarction, Urinary tract infection, Cerebrovascular accident.

Data from ClinicalTrials.gov NCT02579096 adverse events section.

Sponsor's own description

This trial will compare two effective therapies, allopurinol and febuxostat, to lower serum uric acid and therefore prevent further gout attacks. These therapies have never been compared at appropriate doses. Further, they will be studied in patients with kidney disease for the first time.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Management of gout in chronic kidney disease: a G-CAN Consensus Statement on the research priorities.
    Stamp LK, Farquhar H, Pisaniello HL, Vargas-Santos AB, et al · · 2021 · cited 51× · PMID 34331037 · DOI 10.1038/s41584-021-00657-4
  2. Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management.
    O'Dell JR, Brophy MT, Pillinger MH, Neogi T, et al · · 2022 · cited 49× · PMID 35434725 · DOI 10.1056/evidoa2100028
  3. Initiating guideline-concordant gout treatment improves arterial endothelial function and reduces intercritical inflammation: a prospective observational study.
    Toprover M, Shah B, Oh C, Igel TF, et al · · 2020 · cited 16× · PMID 32653044 · DOI 10.1186/s13075-020-02260-6
  4. Determinants of Achieving Serum Urate Goal with Treat-to-Target Urate-Lowering Therapy in Gout.
    Helget LN, O'Dell JR, Newcomb JA, Androsenko M, et al · · 2024 · cited 14× · PMID 37842953 · DOI 10.1002/art.42731
  5. Past, present and future of xanthine oxidase inhibitors: design strategies, structural and pharmacological insights, patents and clinical trials.
    Singh A, Singh K, Sharma A, Kaur K, et al · · 2023 · cited 10× · PMID 37974965 · DOI 10.1039/d3md00316g
  6. Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial.
    Barry A, Helget LN, Androsenko M, Wu H, et al · · 2024 · cited 6× · PMID 38925627 · DOI 10.1002/art.42927
  7. Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators.
    Sanchez C, Campeau A, Liu-Bryan R, Mikuls TR, et al · · 2024 · cited 3× · PMID 39426967 · DOI 10.1038/s41598-024-74154-5
  8. Real-world persistence of urate-lowering therapy following a treat-to-target intervention: A two-year follow-up analysis of the STOP gout trial.
    Kohn S, Sayles H, Helget LN, England BR, et al · · 2025 · PMID 40782426 · DOI 10.1016/j.semarthrit.2025.152800

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