Gollnick 2001.

Methods	Parallel design, randomised controlled trial
Participants	85 participants from 10 centres in Germany, Austria and Switzerland Inclusion criteria: Phase 1: male participants over 16 years of age with severe inflammatory/nodular forms of facial acne (acne conglobata, acne papulopustulosa nodosa and acne nodulocystica); severity of the acne being at least grade 4 using Cunliffe's classification (Leeds scale); having at least 2 deep inflammatory lesions (nodes, cysts or nodules) and other papules and pustules Phase 2: very good therapeutic improvement during the whole period of study phase 1 for immediate subsequent admission; very good clinical improvement achieved prematurely, before completing the 6 months of study phase 1, for early transference to study phase 2 Exclusion criteria: women, participants with milder (comedonal or papulopustular acne) or more severe (acne fulminans, acne tetrade) forms of acne, photosensitive participants, and participants with contraindications to isotretinoin or minocycline, and those hypersensitive to the excipients contained in the azelaic acid cream Age: for all participants, mean/range (years): 19/15 ‐ 31 Group 1: 19/16 ‐ 31 Group 2: 19/15 ‐ 27 Gender: 100% male Duration of acne: mean/range (years): 4/0 ‐ 14 Group 1: 4/ 0 ‐ 14 Group 2: 3/0 ‐ 10 Acne severity: 100% severe
Interventions	AA/Mino group (n = 50): 6‐month study phase 1: 20% azelaic acid cream, twice daily to affected areas, plus oral minocycline, 50 mg, twice daily  3‐month study phase 2 (maintenance treatment period): 20% azelaic acid cream twice daily Iso group (n = 35): 6‐month study phase 1: oral isotretinoin ‐ initial dose (month 1) was 0.8 mg/kg, decreasing in month 2 to 0.7 mg/kg, in month 3 to 0.5‐0.7 mg/kg and in months 4‐6 to 0.5 mg/kg per day 3‐month study phase 2 (maintenance treatment period): no therapy
Outcomes	Primary efficacy outcome: Changes in the number of facial papules, pustules and deep inflammatory acne lesions assessed at every examination* Secondary efficacy outcomes: The investigator's and the participant's subjective global assessment of the therapeutic result (classified as "very good, good, moderate, no improvement, deterioration") measured at each examination* Other outcomes: Degree of seborrhoea assessed at each examination Adverse effects (clinical and laboratory) and subjective complaints evaluated at each participant examination and documented by nature, severity, and duration at every visit* Patient examinations were done for all participants at baseline and at monthly intervals over the 6‐month treatment period in study phase 1. In study phase 2, participants of the initial AA/mino group were examined at monthly intervals over the 3‐month maintenance treatment period, but the participants of the initial Iso group were examined only once (after completion of the second 3‐month study phase). * Indicates outcomes which matched those prespecified for this review
Funding body	None stated
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: The trial did not provide any information about random sequence generation
Allocation concealment (selection bias)	Unclear risk	Comment: There was no statement regarding methods of allocation concealment in the study
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "...the study design was essentially open label..." Comment: Participants and personnel were not blinded; they were aware of the treatment arm to which participants were allocated
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "...the study design was essentially open label..." Comment: The study had an open design. However, there was no information regarding blinding of outcome assessors
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Of the 85 eligible patients recruited to the study, 77 completed the first study phase (90.6%). Eight patients (6 from the AA/Mino group, 2 from the Iso group) dropped out of the study because of poor compliance, adverse reactions, lack of efficacy, infringement of the study protocol or for other reasons. All 85 patients were included in the analysis of the efficacy. " Comment: The level of loss to follow‐up could lead to a considerable attrition bias. Reasons for attrition were described, but there was imbalance of missing data between intervention groups
Selective reporting (reporting bias)	High risk	Comment: No protocol available; data from participants subjective global assessment of improvement after therapy were not reported, despite having been listed in the methods section
Other bias	Low risk	Comment: There were no other apparent sources of bias