CSP594 Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Detailed Description
Gout is the most common form of inflammatory arthritis affecting adults (1), with a disease frequency that continues to increase dramatically (2). Gout is associated with substantial morbidity and mortality which are concentrated in older men and magnified in patients with chronic kidney disease (CKD) (3-6), demographics common to the Veterans Affairs (VA) Health System. Effective gout therapies are readily available and are centered primarily on the use of approved urate lowering therapy (ULT). Despite having excellent ULT options available to patients (7), gout is extremely poorly managed especially in patients with CKD (8-10).
The two most widely used ULTs in clinical practice, allopurinol and febuxostat, have recently been endorsed as the two acceptable first-line treatment strategies in chronic gout (7). Although both agents appear to be efficacious and generally well-tolerated, allopurinol and febuxostat have significantly different costs and have never been compared to each other at appropriate doses. Randomized controlled trials completed to date comparing allopurinol with febuxostat in gout have used 'fixed' and, in many cases, insufficient doses of allopurinol (11-13), an approach that is contrary to current guideline recommendations (7). Furthermore, these studies have included only very small proportions of gout patients with CKD even though CKD is present in approximately 1 of every 2 gout sufferers (14).
To test the hypothesis that allopurinol is non-inferior to febuxostat in the treatment of gout, the investigators propose a randomized open-label non-inferiority trial, which for the first time compares allopurinol with febuxostat using appropriately titrated doses and a "treat-to-target" approach. Further, the investigators will assess the comparative effectiveness of these agents in a significant number of gout patients with co-morbid CKD.
The investigators plan to enroll 950 participants with a diagnosis of gout, including participants with stage 3 CKD, who are hyperuricemic defined as a serum uric acid concentration (sUA) above 6.8 mg/dl. Participants will be recruited from 18 Veteran Affairs and 5 Rheumatology and Arthritis Investigational Network (RAIN) sites. The total duration of the trial will be 4 years. Recruitment will occur over 24 months. Participants will be followed for 72 weeks. This will include a 24 week Dose Titration Phase (Phase 1) followed by a 24 week Maintenance and Optimization Phase (Phase 2) and then a 24 week Steady State Flare Observation Phase (Phase 3). The investigators will use a "treat-to-target" approach with specified titration of ULT dosing to obtain goal sUA. Maximal daily drug doses will be 800 mg/day for allopurinol or 120 mg/day for febuxostat.
The primary outcome will be the proportion of participants who have at least one gout flare in the allopurinol group compared to the febuxostat group during Phase 3. This primary outcome was endorsed by the patient and VA provider groups that were surveyed (see below). All participants will be followed during Phase 3 regardless of the achievement of sUA goal. The primary hypothesis will test the non-inferiority of allopurinol with regards to proportions of flares. The investigators anticipate that approximately 15 to 20% of patients will flare during Phase 3.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Allopurinol / Sham Comparator (Febuxostat) Patients will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling Febuxostat will be given with allopurinol |
Drug: allopurinol capsule, 100-800 mg by mouth once daily
Patients will be up-titrated up to the dose required to reach target uric acid levels.
Other Names:
Drug: Placebo, vehicle control (febuxostat-shaped)
Placebo tablets resembling febuxostat will be given with allopurinol.
|
Active Comparator: Febuxostat / Sham Comparator (Allopurinol) Febuxostat will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling Allopurinol will be given with Febuxostat |
Drug: febuxostat tablet 40-120 mg by mouth once daily
Patients will be up-titrated to the dose required to reach target uric acid levels.
Other Names:
Drug: Placebo, vehicle control (allopurinol-shaped)
Placebo capsules resembling allopurinol will be given with febuxostat.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Experiencing ≥ 1 Gout Flare During Phase 3 [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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18 years
-
History of gout - crystal proven or historical as defined by ACR criteria listed above
-
Serum urate level > 6.8 mg/dl
Exclusion Criteria:
-
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
-
Ascites
-
Encephalopathy
-
Current use of azathioprine, mercaptopurine, didanosine, cyclophosphamide, probenecid, lesinurad or pegloticase
-
Enrollment in another randomized interventional clinical trial
-
Any severe medical condition that, in the enrolleer's opinion, is likely to compromise the participant's ability to complete the trial
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | VA Loma Linda Healthcare System, Loma Linda, CA | Loma Linda | California | United States | 92357 |
2 | VA San Diego Healthcare System, San Diego, CA | San Diego | California | United States | 92161 |
3 | San Francisco VA Medical Center, San Francisco, CA | San Francisco | California | United States | 94121 |
4 | Miami VA Healthcare System, Miami, FL | Miami | Florida | United States | 33125 |
5 | Edward Hines Jr. VA Hospital, Hines, IL | Hines | Illinois | United States | 60141-5000 |
6 | VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA | Boston | Massachusetts | United States | 02130 |
7 | Minneapolis VA Health Care System, Minneapolis, MN | Minneapolis | Minnesota | United States | 55417 |
8 | Mayo Clinic Rochester MN ? RAIN 1 | Rochester | Minnesota | United States | 55905 |
9 | Kansas City VA Medical Center, Kansas City, MO | Kansas City | Missouri | United States | 64128 |
10 | Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE | Omaha | Nebraska | United States | 68105-1873 |
11 | University of Nebraska Medical Center ? RAIN 5 | Omaha | Nebraska | United States | 68198-3025 |
12 | Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY | New York | New York | United States | 10010 |
13 | Asheville VA Medical Center, Asheville, NC | Asheville | North Carolina | United States | 28805 |
14 | Sanford Bismarck Medical Center ? RAIN 2 | Bismarck | North Dakota | United States | 58506 |
15 | Cincinnati VA Medical Center, Cincinnati, OH | Cincinnati | Ohio | United States | 45220 |
16 | VA Portland Health Care System, Portland, OR | Portland | Oregon | United States | 97239 |
17 | Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA | Philadelphia | Pennsylvania | United States | 19104 |
18 | VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA | Pittsburgh | Pennsylvania | United States | 15240 |
19 | Yankton Medical Clinic ? RAIN 3 | Yankton | South Dakota | United States | 57078 |
20 | VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX | Dallas | Texas | United States | 75216 |
21 | VA Salt Lake City Health Care System, Salt Lake City, UT | Salt Lake City | Utah | United States | 84148 |
22 | White River Junction VA Medical Center, White River Junction, VT | White River Junction | Vermont | United States | 05009-0001 |
23 | Salem VA Medical Center, Salem, VA | Salem | Virginia | United States | 24153 |
Sponsors and Collaborators
- VA Office of Research and Development
Investigators
- Study Chair: James R O'Dell, Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
Study Documents (Full-Text)
More Information
Publications
None provided.- 594
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Total of 950 subjects were enrolled into the study. However, 10 subjects were excluded from study participation : 3 due to screening errors 7 dropped out before receiving study treatment |
Arm/Group Title | Allopurinol / Sham Comparator (Febuxostat) | Febuxostat / Sham Comparator (Allopurinol) |
---|---|---|
Arm/Group Description | Patients will be up-titrated up to the dose required to reach target uric acid levels. Allopurinol: allopurinol capsule, 100-800 mg by mouth once daily Placebo: tablets resembling febuxostat will be given with allopurinol. | Patients will be up-titrated to the dose required to reach target uric acid levels. Febuxostat: tablet 40-120 mg by mouth once daily Placebo: capsules resembling allopurinol will be given with febuxostat. |
Period Title: Phase 1, Weeks 0 - 24 | ||
STARTED | 468 | 472 |
COMPLETED | 411 | 422 |
NOT COMPLETED | 57 | 50 |
Period Title: Phase 1, Weeks 0 - 24 | ||
STARTED | 411 | 422 |
COMPLETED | 389 | 391 |
NOT COMPLETED | 22 | 31 |
Period Title: Phase 1, Weeks 0 - 24 | ||
STARTED | 389 | 391 |
COMPLETED | 367 | 373 |
NOT COMPLETED | 22 | 18 |
Baseline Characteristics
Arm/Group Title | Allopurinol / Sham Comparator (Febuxostat) | Febuxostat / Sham Comparator (Allopurinol) | Total |
---|---|---|---|
Arm/Group Description | Patients will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling febuxostat will be given with allopurinol allopurinol: Patients will be titrated up to the dose that will lower to target uric acid levels. Placebo, vehicle control (febuxostat-shaped): Placebo in the shape of febuxostat will be given with allopurinol | febuxostat will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling Allopurinol will be given with febuxostat febuxostat: febuxostat will be titrated up to the dose that will lower to target uric acid levels. Placebo, vehicle control (allopurinol-shaped): Placebo in the shape of allopurinol will be given with febuxostat | Total of all reporting groups |
Overall Participants | 468 | 472 | 940 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
62.9
(11.8)
|
61.3
(12.9)
|
62.1
(12.4)
|
Sex: Female, Male (Count of Participants) | |||
Female |
7
1.5%
|
8
1.7%
|
15
1.6%
|
Male |
461
98.5%
|
464
98.3%
|
925
98.4%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
20
4.3%
|
27
5.7%
|
47
5%
|
Not Hispanic or Latino |
444
94.9%
|
443
93.9%
|
887
94.4%
|
Unknown or Not Reported |
4
0.9%
|
2
0.4%
|
6
0.6%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
3
0.6%
|
2
0.4%
|
5
0.5%
|
Asian |
14
3%
|
15
3.2%
|
29
3.1%
|
Native Hawaiian or Other Pacific Islander |
10
2.1%
|
9
1.9%
|
19
2%
|
Black or African American |
104
22.2%
|
102
21.6%
|
206
21.9%
|
White |
315
67.3%
|
322
68.2%
|
637
67.8%
|
More than one race |
10
2.1%
|
7
1.5%
|
17
1.8%
|
Unknown or Not Reported |
12
2.6%
|
15
3.2%
|
27
2.9%
|
CKD3 (Count of Participants) | |||
Count of Participants [Participants] |
181
38.7%
|
170
36%
|
351
37.3%
|
Tophus (Count of Participants) | |||
Count of Participants [Participants] |
81
17.3%
|
71
15%
|
152
16.2%
|
sUA >= 9 mg/dL (Count of Participants) | |||
Count of Participants [Participants] |
160
34.2%
|
148
31.4%
|
308
32.8%
|
Pre-study allopurinol users with dose <= 300 mg (Count of Participants) | |||
Count of Participants [Participants] |
178
38%
|
167
35.4%
|
345
36.7%
|
Outcome Measures
Title | Percentage of Participants Experiencing ≥ 1 Gout Flare During Phase 3 |
---|---|
Description | 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 |
Time Frame | Phase III of the study (weeks 49-72 of study duration) |
Outcome Measure Data
Analysis Population Description |
---|
Primary analysis excluded patients who either never received the trial interventions, or were identified as ineligible after randomization, or dropouts; a complete case analysis was conducted on total of 749 subjects: 740 who completed phase 3 of the study plus 9 subjects who terminated in phase 3 after having an outcome. |
Arm/Group Title | Allopurinol / Sham Comparator (Febuxostat) | Febuxostat / Sham Comparator (Allopurinol) |
---|---|---|
Arm/Group Description | Patients will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling Febuxostat will be given with allopurinol Allopurinol: Patients will be titrated up to the dose that will lower to target uric acid levels. Placebo, vehicle control (Febuxostat-shaped): Placebo in the shape of Febuxostat will be given with Allopurinol | Febuxostat will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling Allopurinol will be given with Febuxostat Febuxostat: Febuxostat will be titrated up to the dose that will lower to target uric acid levels. Placebo, vehicle control (Allopurinol-shaped): Placebo in the shape of Allopurinol will be given with Febuxostat |
Measure Participants | 370 | 379 |
Count of Participants [Participants] |
135
28.8%
|
165
35%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Allopurinol / Sham Comparator (Febuxostat), Febuxostat / Sham Comparator (Allopurinol) |
---|---|---|
Comments | One-sided null hypothesis posited that allopurinol was inferior to febuxostat. The proportions of participants with ≥ 1 gout flare during phase 3 were compared between the two treatments. | |
Type of Statistical Test | Non-Inferiority | |
Comments | A non-inferiority bound of 8% was established during the trial design; a one-sided alpha level was set at 0.05. | |
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Risk Difference (RD) |
Estimated Value | -7 | |
Confidence Interval |
(1-Sided) 95% to -1.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | Beginning at informed consent and continuing until the end of participation in the study at 72 weeks, plus 30 days of observation. | |||
---|---|---|---|---|
Adverse Event Reporting Description | Data on adverse events was collected spontaneously through patient reports, actively elicited during visits through open-ended questioning and examination, and gathered at the time of telephone contact and medical record reviews during the follow-up period. | |||
Arm/Group Title | Allopurinol / Sham Comparator (Febuxostat) | Febuxostat / Sham Comparator (Allopurinol) | ||
Arm/Group Description | Patients will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling Febuxostat will be given with allopurinol Allopurinol: Patients will be titrated up to the dose that will lower to target uric acid levels. Placebo, vehicle control (Febuxostat-shaped): Placebo in the shape of Febuxostat will be given with Allopurinol | Febuxostat will be titrated up to the dose that will lower to target uric acid levels. A placebo resembling Allopurinol will be given with Febuxostat Febuxostat: Febuxostat will be titrated up to the dose that will lower to target uric acid levels. Placebo, vehicle control (Allopurinol-shaped): Placebo in the shape of Allopurinol will be given with Febuxostat | ||
All Cause Mortality |
||||
Allopurinol / Sham Comparator (Febuxostat) | Febuxostat / Sham Comparator (Allopurinol) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 8/468 (1.7%) | 8/472 (1.7%) | ||
Serious Adverse Events |
||||
Allopurinol / Sham Comparator (Febuxostat) | Febuxostat / Sham Comparator (Allopurinol) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 125/468 (26.7%) | 123/472 (26.1%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 2/468 (0.4%) | 5 | 3/472 (0.6%) | 5 |
Iron deficiency anaemia | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Spontaneous haematoma | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Cardiac disorders | ||||
Angina unstable | 4/468 (0.9%) | 4 | 3/472 (0.6%) | 4 |
Arrhythmia supraventricular | 12/468 (2.6%) | 18 | 8/472 (1.7%) | 11 |
Atrioventricular block complete | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Bradycardia | 3/468 (0.6%) | 3 | 0/472 (0%) | 0 |
Cardiac failure | 27/468 (5.8%) | 56 | 12/472 (2.5%) | 19 |
Coronary artery disease | 3/468 (0.6%) | 3 | 2/472 (0.4%) | 2 |
Hypertensive cardiomyopathy | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Ischaemic cardiomyopathy | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Mitral valve disease | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Myocardial infarction | 4/468 (0.9%) | 4 | 8/472 (1.7%) | 8 |
Myocardial ischaemia | 2/468 (0.4%) | 2 | 0/472 (0%) | 0 |
Palpitations | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Pulseless electrical activity | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Sinus node dysfunction | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Tachycardia | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Ventricular fibrillation | 0/468 (0%) | 0 | 2/472 (0.4%) | 3 |
Ventricular tachycardia | 1/468 (0.2%) | 1 | 2/472 (0.4%) | 2 |
Endocrine disorders | ||||
Hypothyroidism | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Gastrointestinal disorders | ||||
Abdominal discomfort | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Abdominal pain | 2/468 (0.4%) | 2 | 2/472 (0.4%) | 3 |
Ascites | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Diarrhoea | 1/468 (0.2%) | 1 | 1/472 (0.2%) | 1 |
Duodenal ulcer haemorrhage | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Erosive oesophagitis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Gastrointestinal angiodysplasia | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Gastrointestinal haemorrhage | 3/468 (0.6%) | 3 | 2/472 (0.4%) | 2 |
Gastrooesophageal reflux disease | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Glossitis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Haematemesis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Ileus | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Incarcerated umbilical hernia | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Inguinal hernia | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Melaena | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Pancreatitis | 2/468 (0.4%) | 2 | 1/472 (0.2%) | 1 |
Pancreatitis chronic | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Rectal haemorrhage | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Small intestinal obstruction | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Vomiting | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
General disorders | ||||
Adverse drug reaction | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Asthenia | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Cardiac death | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Chest pain | 5/468 (1.1%) | 5 | 4/472 (0.8%) | 4 |
Non-cardiac chest pain | 0/468 (0%) | 0 | 1/472 (0.2%) | 2 |
Hepatobiliary disorders | ||||
Cholecystitis | 5/468 (1.1%) | 5 | 2/472 (0.4%) | 2 |
Cholelithiasis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Hepatic cirrhosis | 1/468 (0.2%) | 1 | 1/472 (0.2%) | 1 |
Liver injury | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Immune system disorders | ||||
Anaphylactic reaction | 1/468 (0.2%) | 1 | 1/472 (0.2%) | 1 |
Infections and infestations | ||||
Abdominal abscess | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Abscess limb | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Acute haemorrhagic conjunctivitis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Anal abscess | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Appendicitis | 2/468 (0.4%) | 2 | 0/472 (0%) | 0 |
Arthritis bacterial | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Bacteraemia | 2/468 (0.4%) | 2 | 0/472 (0%) | 0 |
Bacterial infection | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Bronchitis | 1/468 (0.2%) | 1 | 2/472 (0.4%) | 2 |
Bursitis infective | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
COVID-19 | 0/468 (0%) | 0 | 2/472 (0.4%) | 2 |
Cellulitis | 6/468 (1.3%) | 6 | 12/472 (2.5%) | 15 |
Diabetic foot infection | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Diverticulitis | 0/468 (0%) | 0 | 3/472 (0.6%) | 3 |
Gangrene | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Gastroenteritis | 1/468 (0.2%) | 1 | 2/472 (0.4%) | 2 |
Groin abscess | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Infection | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Influenza | 2/468 (0.4%) | 2 | 2/472 (0.4%) | 2 |
Liver abscess | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Localised infection | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Osteomyelitis | 2/468 (0.4%) | 4 | 3/472 (0.6%) | 3 |
Pneumonia | 10/468 (2.1%) | 11 | 9/472 (1.9%) | 10 |
Postoperative wound infection | 3/468 (0.6%) | 3 | 0/472 (0%) | 0 |
Respiratory syncytial virus infection | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Sepsis | 2/468 (0.4%) | 2 | 6/472 (1.3%) | 8 |
Tonsillitis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Upper respiratory tract infection | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Urinary tract infection | 0/468 (0%) | 0 | 7/472 (1.5%) | 8 |
Urosepsis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Injury, poisoning and procedural complications | ||||
Chest injury | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Fall | 6/468 (1.3%) | 6 | 3/472 (0.6%) | 3 |
Hip fracture | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Post procedural haemorrhage | 2/468 (0.4%) | 2 | 0/472 (0%) | 0 |
Road traffic accident | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Skin laceration | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Subdural haematoma | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Traumatic haematoma | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Vascular pseudoaneurysm | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Wound | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Wound necrosis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Investigations | ||||
Electrocardiogram abnormal | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
International normalised ratio increased | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Metabolism and nutrition disorders | ||||
Dehydration | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Diabetic ketoacidosis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Electrolyte imbalance | 0/468 (0%) | 0 | 3/472 (0.6%) | 3 |
Failure to thrive | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Fluid overload | 3/468 (0.6%) | 3 | 0/472 (0%) | 0 |
Gout | 3/468 (0.6%) | 3 | 2/472 (0.4%) | 2 |
Hyperglycaemia | 2/468 (0.4%) | 2 | 5/472 (1.1%) | 5 |
Hyperkalaemia | 2/468 (0.4%) | 2 | 4/472 (0.8%) | 4 |
Hypoglycaemia | 1/468 (0.2%) | 1 | 4/472 (0.8%) | 4 |
Hypokalaemia | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Hyponatraemia | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Hypovolaemia | 1/468 (0.2%) | 1 | 1/472 (0.2%) | 1 |
Malnutrition | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Obesity | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||
Back pain | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Flank pain | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Gouty arthritis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Myalgia | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Myopathy toxic | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Neck pain | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Osteoarthritis | 2/468 (0.4%) | 2 | 1/472 (0.2%) | 1 |
Spinal osteoarthritis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Spinal stenosis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Vertebral column mass | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Astrocytoma | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Bladder cancer recurrent | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Hepatocellular carcinoma | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Invasive ductal breast carcinoma | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Lung adenocarcinoma | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Lung neoplasm malignant | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Metastatic malignant melanoma | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Metastatic squamous cell carcinoma | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Myelofibrosis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Pancreatic carcinoma metastatic | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Prostate cancer | 2/468 (0.4%) | 2 | 3/472 (0.6%) | 3 |
Squamous cell carcinoma | 1/468 (0.2%) | 1 | 1/472 (0.2%) | 1 |
Tracheal cancer | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Nervous system disorders | ||||
Carotid artery stenosis | 2/468 (0.4%) | 2 | 2/472 (0.4%) | 2 |
Cerebrovascular accident | 2/468 (0.4%) | 2 | 7/472 (1.5%) | 7 |
Dementia | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Dizziness | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Encephalopathy | 0/468 (0%) | 0 | 3/472 (0.6%) | 3 |
Generalised tonic-clonic seizure | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Headache | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
IIIrd nerve paresis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Migraine | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Myasthenia gravis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Radiculopathy | 2/468 (0.4%) | 2 | 0/472 (0%) | 0 |
Syncope | 2/468 (0.4%) | 3 | 1/472 (0.2%) | 1 |
Transient ischaemic attack | 0/468 (0%) | 0 | 2/472 (0.4%) | 2 |
Psychiatric disorders | ||||
Alcohol withdrawal syndrome | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Alcoholism | 2/468 (0.4%) | 2 | 2/472 (0.4%) | 2 |
Delirium | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Depression | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Post-traumatic stress disorder | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Substance abuse | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Substance use disorder | 1/468 (0.2%) | 1 | 1/472 (0.2%) | 1 |
Suicidal ideation | 2/468 (0.4%) | 5 | 0/472 (0%) | 0 |
Suicide attempt | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Renal and urinary disorders | ||||
Acute kidney injury | 19/468 (4.1%) | 24 | 12/472 (2.5%) | 12 |
Nephrolithiasis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Renal failure | 2/468 (0.4%) | 2 | 0/472 (0%) | 0 |
Renal impairment | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Renal mass | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Urinary tract obstruction | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||
Aspiration | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Asthma | 0/468 (0%) | 0 | 1/472 (0.2%) | 3 |
Chronic obstructive pulmonary disease | 7/468 (1.5%) | 10 | 4/472 (0.8%) | 6 |
Cough | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Dyspnoea | 2/468 (0.4%) | 2 | 1/472 (0.2%) | 1 |
Epistaxis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Haemoptysis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Interstitial lung disease | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Laryngeal stenosis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Lung hernia | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Pulmonary embolism | 1/468 (0.2%) | 2 | 3/472 (0.6%) | 3 |
Pulmonary hypertension | 1/468 (0.2%) | 2 | 0/472 (0%) | 0 |
Respiratory failure | 5/468 (1.1%) | 5 | 4/472 (0.8%) | 5 |
Skin and subcutaneous tissue disorders | ||||
Angioedema | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Drug eruption | 2/468 (0.4%) | 2 | 0/472 (0%) | 0 |
Surgical and medical procedures | ||||
Alcohol detoxification | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Aneurysm repair | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Cardiac ablation | 2/468 (0.4%) | 2 | 0/472 (0%) | 0 |
Cholecystectomy | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Haemorrhoid operation | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Hip arthroplasty | 2/468 (0.4%) | 2 | 2/472 (0.4%) | 2 |
Knee arthroplasty | 2/468 (0.4%) | 2 | 4/472 (0.8%) | 4 |
Lung lobectomy | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Metabolic surgery | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Nephrectomy | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Pancreaticosplenectomy | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Peripheral artery bypass | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Prostatic operation | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Shoulder arthroplasty | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Skin operation | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Spinal fusion surgery | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Spinal laminectomy | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Spinal operation | 0/468 (0%) | 0 | 2/472 (0.4%) | 2 |
Surgery | 1/468 (0.2%) | 1 | 1/472 (0.2%) | 1 |
Tenoplasty | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Thyroidectomy | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Transurethral prostatectomy | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Vascular disorders | ||||
Aortic aneurysm | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Aortic stenosis | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Deep vein thrombosis | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Dry gangrene | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Haematoma | 0/468 (0%) | 0 | 1/472 (0.2%) | 1 |
Hypertension | 5/468 (1.1%) | 5 | 0/472 (0%) | 0 |
Hypotension | 2/468 (0.4%) | 2 | 2/472 (0.4%) | 2 |
Orthostatic hypotension | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Peripheral ischaemia | 1/468 (0.2%) | 1 | 0/472 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Allopurinol / Sham Comparator (Febuxostat) | Febuxostat / Sham Comparator (Allopurinol) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 36/468 (7.7%) | 44/472 (9.3%) | ||
Gastrointestinal disorders | ||||
Abdominal discomfort | 1/468 (0.2%) | 1 | 5/472 (1.1%) | 5 |
Diarrhoea | 4/468 (0.9%) | 4 | 8/472 (1.7%) | 9 |
Nausea | 3/468 (0.6%) | 3 | 6/472 (1.3%) | 7 |
Investigations | ||||
Alanine aminotransferase increased | 18/468 (3.8%) | 18 | 21/472 (4.4%) | 22 |
Skin and subcutaneous tissue disorders | ||||
Drug eruption | 11/468 (2.4%) | 11 | 11/472 (2.3%) | 11 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Ryan E. Ferguson, ScD, MPH, Director |
---|---|
Organization | Boston CSP Coordinating Center |
Phone | 1-857-364-4201 |
Ryan.Ferguson@va.gov |
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