Selby 2007.

Methods	Prospective, parallel, stratified to thiopurine usage, randomized, double‐blind, placebo‐controlled, 3 year trial with induction phase (16 weeks), maintenance phase (16‐104 weeks) and follow‐up phase (104‐156 weeks)
Participants	Patients (over 18 years old) with active Crohn's Disease (CD Activity Index (CDAI) > 200) diagnosed with standard criteria enrolled from 20 Australian centres. Exclusion Criteria: patients with: isolated upper gastrointestinal or isolated perianal disease or a stoma; patients requiring: intravenous corticosteroids at initial assessment and/or those thought likely to require surgery during the first 4 months of the study; patients who had received antibiotics for Crohn’s disease within 1 month of entry to the study or had used infliximab N = 213; Induction Phase: Intervention (n = 111) vs Placebo (n = 102) Maintenace Phase: Period 1: Week 16‐52: Intervention (n = 67) vs Placebo (n = 55) Period 2: Week 53‐104: Intervention (n = 42) vs Placebo (n = 28) Follow‐up Phase: Intervention (n = 34) vs Placebo (n = 20)
Interventions	Combination therapy with clarithromycin, rifabutin, and clofazimine or placebo Adjunct therapy included a 16‐week tapering course of oral prednisolone (starting with 40 mg/day to 0 mg/day) for both intervention and placebo groups Intervention combination: clarithromycin 250 mg/day for week 1, 250 mg twice per day for week 2+3, 750 mg/day from week 4 rifabutin 150 mg/day for week 1, 300 mg/day for week 2+3, 450 mg/day from week 4 clofazimine given at 50 mg/day Induction Phase (0‐16 weeks): Combination therapy or placebo; coupled with adjunct therapy Maintenance Phase (17‐104 weeks): Combination therapy or placebo maintained Follow‐up Phase (105‐156 weeks): Trial medications ceased
Outcomes	Primary outcomes: proportion of patients with at least 1 relapse at months 12, 24 and 36 Secondary outcomes: percentage of patients in remission (CDAI < 150) at week 16; number of patients who relapsed by predetermined time periods; length of time to first relapse; intervention and placebo safety profiles; other outcomes (improvements in CDEIS scores, proportion of subjects requiring Crohn's related‐surgery); laboratory profile changes (serum albumin, erythrocyte sedimentation rate and CRP); and quality of life scores (questionnaires)
Notes	Other outcomes monitored included proportion of patients in endoscopic remission at week 156; patient compliance with the drug regime; and maintenance of blinding
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of randomization not described
Allocation concealment (selection bias)	Unclear risk	Method of allocation not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind (both patients and physicians) Placebo was identically matched to the intervention regime and included re‐encapsulated clofazimine using gelatine capsules Blinding was also monitored to ensure it was maintained at various points throughout the study for both patients and physicians Compliance was monitored by pharmacy returns
Incomplete outcome data (attrition bias) All outcomes	Low risk	Drop‐outs balanced across intervention groups with similar reasons for withdrawal
Selective reporting (reporting bias)	Low risk	Primary and secondary outcome data were reported according to study protocol. Quality of life questionnaires were not analysed, but rational was provided
Other bias	Low risk	The study appears to be free of other sources of bias