Introduction
Background and rationale (7)
Objective (8)
Research hypotheses
Study methods
Trial design (9)
Randomization (10)
Implications of trial design
Simulations
Handling of randomization
Sample size (11)
Framework (12)
Statistical interim analyses (13a)
Adjustment of significance level (13b)
Stopping guidance (13c)
Timing of final analysis (14)
Timing of outcome assessment (15)
Statistical principles
Confidence intervals and P values (16)
Multiplicity corrections (17)
Confidence intervals to be reported (18)
Adherence and protocol deviations (19a-d)
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Incomplete use of medication
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Subsequent realization of exclusion criteria according to paragraph 8.3 of the study protocol
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Acute gout flare lasted longer than 48 h* prior initial medication
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A different underlying disease has been noticed, e.g., septic arthritis
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Attrition prior day 6
Analysis populations (20)
Trial population
Screening data (21)
Eligibility (22)
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Patients ≥ 18 years of age
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Clinical diagnosis of acute gout attack (symptoms: pain, swelling, tenderness, skin reddening or local hyperthermia)
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Acute pain in the hand or foot (podagra, chiragra)
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The onset of pain was no more than 2* calendar days ago (e.g., presentation on Monday afternoon, onset of pain on Saturday morning)
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Willingness to participate in the study and ability to give written informed consent
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Known intolerance or contraindication to colchicine or prednisolone
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Known intolerance to the placebo (e.g., lactose intolerance)
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Existing or less than 2 weeks previous oral treatment with corticosteroids or colchicine
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Known chronic kidney disease (CKD stage ≥ 4) or available value of eGFR < 30 ml/min/1.73 m2
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Known blood formation disorder or available values of platelets < 30,000 μl or leukocytes < 4000 μl or Hb <5 mmol/l or 8 g/dl [27]
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Uncontrolled high blood pressure (systolic blood pressure permanently above 160 mmHg)
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Known liver cirrhosis or severe liver disease or available liver enzymes results (i.e., serum glutamate oxalate transaminase (GOT/ASAT) and serum glutamic pyruvic transaminase (GPT/ALAT)) with 2-fold elevation over the respective reference range
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Known current gastric or duodenal ulcer (diagnosed in the last 4 weeks)
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Current chemotherapy or chemotherapy completed less than 3 months ago
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Known HIV infection
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Solid organ transplant with immunosuppression
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Desire to have children within the next 6 months (men and women)
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Pregnancy or breastfeeding
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Participation in other studies under the German Medicines Act in the last 3 months
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Previous participation in the COPAGO trial
Recruitment (23)
Withdrawal/loss to follow-up (24a–c)
Baseline patient characteristics (25a–b)
Characteristic | Colchicine | Prednisolone | All |
---|---|---|---|
N | na | na | na |
Age, mean (SD) | na | na | na |
Gender | |||
Male, n (%) | na | na | na |
Female, n (%) | na | na | na |
Non-binary, n (%) | na | na | na |
Disease duration, years (SD) | na | na | na |
< 2 years | na | na | na |
2–5 years | na | na | na |
6–10 years | na | na | na |
> 10 years | na | na | na |
Missing, n (%) | na | na | na |
First instance of gout, n (%) | na | na | na |
Missing, n (%) | na | na | na |
Time since symptom onset, hours (SD) | na | na | na |
Missing, n (%) | na | na | na |
Prior pain medication (yes), n (%) | na | na | na |
Missing, n (%) | na | na | na |
Affected body part | na | na | na |
First MTPJ, n (%) | na | na | na |
Other foot joint, n (%) | na | na | na |
Joint of finger and/or hand, n (%) | na | na | na |
Missing, n (%) | na | na | na |
No. of affected body parts | |||
1 | na | na | na |
2 | na | na | na |
3 | na | na | na |
Missing, n (%) | na | na | na |
Pain (NRS), mean (SD) | na | na | na |
Missing, n (%) | na | na | na |
Swollen joint count, n (%) | |||
1 | na | na | na |
2 | na | na | na |
≥ 3 | na | na | na |
Missing, n (%) | na | na | na |
Tender joint count, n (%) | |||
1 | na | na | na |
2 | na | na | na |
>=3 | na | na | na |
Missing, n (%) | na | na | na |
Comorbidities | |||
Diabetes (type I/II), n (%) | na | na | na |
Previous cardiovascular event (coronary heart disease, peripheral artery disease, stroke), n (%) | na | na | na |
Hypertension, n (%) | na | na | na |
Systolic blood pressure | na | na | na |
Diastolic blood pressure | na | na | na |
Missing, n (%) | na | na | na |
Leukocytes (μL) mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
Platelets (nL) mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
Erythrocytes (pL) mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
Hemoglobin (mmol/L) mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
Hematocrit () mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
C-reactive protein (CRP) (mg/L) mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
Uric acid (mg/dL) mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
Creatinine (mg/dL) mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
GOT (U/l), mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
GPT (U/l), mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
eGFR (ml/min/1.73 m2) mean, (SD) | na | na | na |
Missing, n (%) | na | na | na |
Analysis
Outcome definitions (26a–c)
Primary efficacy endpoint
Secondary endpoints
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The average levels of most severe pain (last 24h) over days 1 to 6 of follow-up
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Swelling and tenderness of the joint (4-point Likert scale, day 3 after baseline)
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Physical function at day 6 compared to baseline
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Patient’s global assessment of treatment success (measured with 5-point Likert scale, day 6 after baseline)
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Most severe pain (last 24 h, measured by 11-point NRS at day 3 after baseline) depending on disease duration.
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Frequency of use of additional pain medication by treatment group.
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Frequency of use of non-pharmaceutical pain therapies in the treatment groups
Analysis methods (27a–f)
Analysis of the primary outcome
Analysis of secondary outcomes
Adjustment for covariates
Check of assumptions
Alternative methods
Sensitivity analysis
Subgroup analysis
Missing data (28)
Study design
Data management
Analysis
Additional analysis (29)
Harms (30)
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Dizziness
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Nausea
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Vomiting
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Dyspepsia
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Diarrhea
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Constipation
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Abdominal pain
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Headache
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Skin rash
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Other