Afdhal 1991.
| Methods | Randomized with substratification by disease site, double‐blinded, placebo‐controlled trial | |
| Participants | Patients, N = 49 (34 women, 15 men), with active Crohn's Disease confirmed by standard clinical, radiological, and histological criteria. Study participant exclusionary criteria: indication for surgery, including strictures causing bowel obstruction, fistulae, and abscess formation; and pregnancy. active CD Disease Activity Score (DAS) > 10 (Lancet 1978, 2: 955‐57) Phase 1: Intervention group (n = 25) and placebo group (n = 24) Phase 2: Intervention group (n = 16) and placebo group (n = 12) Phase 3: Intervention group (n = 15) and placebo group (n = 12) |
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| Interventions | Clofazimine 100 mg daily Adjunct therapy included prednisone (initial dose of 45 mg daily) tapered over 3 months for both intervention and placebo groups; Phase 1 ‐ steroids tapered over 12 weeks + 100 mg Clofazimine vs. steroids tapered over 12 weeks + placebo; Phase 2 ‐ Clofazimine 100 mg daily vs placebo for 4 weeks; Phase 3 ‐ Clofazimine 100 mg daily vs placebo for 8 months | |
| Outcomes | Remission induction (phase 1) and maintenance of remission (phases 2 & 3); with remission defined as DAS < 5 | |
| Notes | Reference in Lancet to DAS score DAS score was reported for the end of each phase of the trial Side effects experience in each group was provided Disease site effect on outcome was discussed, but no calculation was provided |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomization not described. Contains substratification for disease site; method not described, but matched in control and intervention groups |
| Allocation concealment (selection bias) | Unclear risk | Not described |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Double blinded, control and intervention groups matched for treatment regime (taken once daily), including clofazimine and matching placebo |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Missing outcome data were approximately balanced between intervention and placebo groups across the 3 Phases of the trial, with similar reasons provided, including phase failure, loss to follow‐up or requested withdrawal. Phase 1: Intervention group (n= 25) and placebo group (n= 24) Phase 2: Intervention group (n= 16) and placebo group (n= 12) Phase 3: Intervention group (n= 15) and placebo group (n= 12) Analysis was performed on an intention to treat basis |
| Selective reporting (reporting bias) | Low risk | Expected outcomes (DAS scores, failures) for each phase were reported, including substratification effects and treatment side effects |
| Other bias | Low risk | The study appears to be free of other sources of bias |