CSP594 Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat
CSP #594 - Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat
1 other identifier
interventional
950
1 country
23
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Mar 2017
Longer than P75 for phase_4
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 15, 2015
CompletedFirst Posted
Study publicly available on registry
October 19, 2015
CompletedStudy Start
First participant enrolled
March 6, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 15, 2021
CompletedResults Posted
Study results publicly available
January 11, 2022
CompletedMarch 29, 2024
March 1, 2024
3.9 years
October 15, 2015
December 17, 2021
March 27, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Experiencing ≥ 1 Gout Flare During Phase 3
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
Phase III of the study (weeks 49-72 of study duration)
Study Arms (2)
Allopurinol / Sham Comparator (Febuxostat)
ACTIVE COMPARATORPatients will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling Febuxostat will be given with allopurinol
Febuxostat / Sham Comparator (Allopurinol)
ACTIVE COMPARATORFebuxostat will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling Allopurinol will be given with Febuxostat
Interventions
Patients will be up-titrated up to the dose required to reach target uric acid levels.
Patients will be up-titrated to the dose required to reach target uric acid levels.
Placebo tablets resembling febuxostat will be given with allopurinol.
Placebo capsules resembling allopurinol will be given with febuxostat.
Eligibility Criteria
You may qualify if:
- Age 18 years
- History of gout - crystal proven or historical as defined by ACR criteria listed above
- Serum urate level \> 6.8 mg/dl
You may not qualify if:
- Stage 4 or 5 Chronic Kidney Disease (CKD) - defined as eGFR \< 30 ml/min/1.73 m2
- Women less than 50 years of age
- Patients with a history of prior solid organ / hematopoietic transplantation
- Previous allergy or intolerance to allopurinol or febuxostat
- Patients who are not candidates for any of the recommended prophylactic medications (colchicine, naprosyn or glucocorticoids)
- Patients who in the opinion of the investigator have a high genetic risk for allopurinol hypersensitivity syndrome (AHS\*) unless they have been found to be negative for HLA B5801.
- Previous history of failure to reach target uric acid levels despite therapy with allopurinol at dose \> 300 mg/day
- Prior febuxostat use
- Patients with malignancies that are currently active with exception of non-melanoma skin cancer
- Patients with serum uric acid levels \>15 mg/dl
- Patients with myelodysplasia and hemoglobin of \< 8.5 mg/dL
- Patients with chronic liver disease with more than one of the following:
- INR \> 1.7, not on Warfarin therapy
- Bilirubin 2 mg/dL
- Serum albumin \< 3.5 mg/dL
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
VA Loma Linda Healthcare System, Loma Linda, CA
Loma Linda, California, 92357, United States
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161, United States
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, 94121, United States
Miami VA Healthcare System, Miami, FL
Miami, Florida, 33125, United States
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, 60141-5000, United States
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, 02130, United States
Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417, United States
Mayo Clinic Rochester MN ? RAIN 1
Rochester, Minnesota, 55905, United States
Kansas City VA Medical Center, Kansas City, MO
Kansas City, Missouri, 64128, United States
Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
Omaha, Nebraska, 68105-1850, United States
University of Nebraska Medical Center ? RAIN 5
Omaha, Nebraska, 68198-3025, United States
Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
New York, New York, 10010, United States
Asheville VA Medical Center, Asheville, NC
Asheville, North Carolina, 28805, United States
Sanford Bismarck Medical Center ? RAIN 2
Bismarck, North Dakota, 58506, United States
Cincinnati VA Medical Center, Cincinnati, OH
Cincinnati, Ohio, 45220, United States
VA Portland Health Care System, Portland, OR
Portland, Oregon, 97239, United States
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19104, United States
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Pittsburgh, Pennsylvania, 15240, United States
Yankton Medical Clinic ? RAIN 3
Yankton, South Dakota, 57078, United States
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, 75216, United States
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148, United States
White River Junction VA Medical Center, White River Junction, VT
White River Junction, Vermont, 05009-0001, United States
Salem VA Medical Center, Salem, VA
Salem, Virginia, 24153, United States
Related Publications (5)
Timilsina S, Brittan K, O'Dell JR, Brophy M, Davis-Karim A, Henrie AM, Neogi T, Newcomb J, Palevsky PM, Pillinger MH, Pittman D, Taylor TH, Wu H, Mikuls TR. Design and Rationale for the Veterans Affairs "Cooperative Study Program 594 Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat" Trial. Contemp Clin Trials. 2018 May;68:102-108. doi: 10.1016/j.cct.2018.03.015. Epub 2018 Mar 27.
PMID: 29597007BACKGROUNDO'Dell JR, Brophy MT, Pillinger MH, Neogi T, Palevsky PM, Wu H, Davis-Karim A, Newcomb JA, Ferguson R, Pittman D, Cannon GW, Taylor T, Terkeltaub R, Cannella AC, England BR, Helget LN, Mikuls TR. Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management. NEJM Evid. 2022 Mar;1(3):10.1056/evidoa2100028. doi: 10.1056/evidoa2100028. Epub 2022 Feb 3.
PMID: 35434725RESULTSanchez C, Campeau A, Liu-Bryan R, Mikuls TR, O'Dell JR, Gonzalez DJ, Terkeltaub R. Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators. Sci Rep. 2024 Oct 19;14(1):24598. doi: 10.1038/s41598-024-74154-5.
PMID: 39426967DERIVEDSanchez C, Campeau A, Liu-Bryan R, Mikuls TR, O'Dell JR, Gonzalez DJ, Terkeltaub R. Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement activation and inflammation modulators. Res Sq [Preprint]. 2024 May 9:rs.3.rs-4278877. doi: 10.21203/rs.3.rs-4278877/v1.
PMID: 38766125DERIVEDSanchez C, Campeau A, Liu-Bryan R, Mikuls T, O'Dell J, Gonzalez D, Terkeltaub R. Sustained xanthine oxidase inhibitor treat to target urate lowering therapy rewires a tight inflammation serum protein interactome. Res Sq [Preprint]. 2024 Jan 2:rs.3.rs-3770277. doi: 10.21203/rs.3.rs-3770277/v1.
PMID: 38260556DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Ryan E. Ferguson, ScD, MPH, Director
- Organization
- Boston CSP Coordinating Center
Study Officials
- STUDY CHAIR
James R O'Dell
Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- FED
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 15, 2015
First Posted
October 19, 2015
Study Start
March 6, 2017
Primary Completion
February 1, 2021
Study Completion
April 15, 2021
Last Updated
March 29, 2024
Results First Posted
January 11, 2022
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- After primary and secondary analyses and subsequent publications
- Access Criteria
- Executed data use agreement with CSP Coordinating Center approval
Individual Participant Data will be made available after study closure only to research credentialed Veterans Affairs researchers who submit a valid study question to their IRB of record. A Data Use Agreement will be in effect between the researcher and the coordinating center