Topical hydrogen peroxide versus fusidic acid for non-severe impetigo in Auckland, Aotearoa New Zealand (the TIARA trial): a single-blind, randomised controlled trial

Background: Impetigo is a common skin disease affecting mostly children worldwide. Topical antibiotics are frequently prescribed for non-severe impetigo, but their use has been associated with antimicrobial resistance. We aimed to compare topical antibiotic fusidic acid with topical antiseptic hydrogen peroxide and with simple wound hygiene in management of impetigo lesions in school-aged children in a low socioeconomic, urban setting. Methods: This community-based, single-blind, non-inferiority, randomised controlled trial enrolled children aged 5–13 years. Children with non-severe impetigo were recruited from school health clinics across 51 school sites in Auckland, Aotearoa New Zealand. Children were excluded if they required systemic antibiotics, were immunocompromised, had known allergy to study medication, or current or recent use of antimicrobials. Children were block randomised (1:1:1) to receive topical fusidic acid, topical hydrogen peroxide, or wound hygiene. Each management strategy was used for any impetigo lesions identified at the time of study entry twice daily for 5 days. Investigators were masked to allocation; however, children and nurses were not due to the appearance differences between treatments. Digital images of impetigo lesions were taken on days 0 and 7 and graded by reviewers, masked to treatment allocation. The primary outcome was treatment success defined by improvement on digital image assessed by masked review at day 7 for the analysis population with a 10% non-inferiority margin. This trial is registered with Australian New Zealand Clinical Trials Registry (12616000356460) and is complete. Findings: Between June 2, 2017, and March 18, 2020, 505 children were enrolled and randomly assigned to treatment, of whom 400 were included in the analysis population: fusidic acid (n=157), hydrogen peroxide (n=169), or wound hygiene alone (n=74; an interim safety analysis led to early termination of recruitment in the wound hygiene group). The mean age was 8·4 years (SD 2·1), 175 (44%) of 400 were female and 225 (56%) were male, and ethnicities included children of Māori (117 [29%]), Pacific (256 [64%]), and Aotearoa New Zealand European or other (20 [5%]). Fusidic acid was successful in 132 (84%) of 157 children, hydrogen peroxide successful in 134 (79%) of 169, and wound hygiene successful in 48 (65%) of 74. Overall, hydrogen peroxide did not show non-inferiority compared with fusidic acid; that is, hydrogen peroxide was not as effective (absolute difference –4·8% [90% CI –11·8 to 2·3]). Wound hygiene alone did not show non-inferiority (absolute difference –19·2% [90% CI –29·2 to –9·2). One adverse event of mild erythema was reported with hydrogen peroxide; no systemic adverse events were reported. Interpretation: Topical hydrogen peroxide was not non-inferior to topical fusidic acid for treatment of non-severe impetigo. However, as these infections are mild and the difference in cure rate is small, when balanced with the potential benefits of lessening antimicrobial resistance, topical hydrogen peroxide use in non-severe impetigo management remains reasonable. Children and families should be provided with appropriate advice regarding review for non-resolving or deteriorating lesions. Funding: Cure Kids New Zealand, Auckland District Health Board Charitable Trust (A+ Trust), Tupu Research Grant, Ko Awatea, The New Zealand Wound Care Society, the Joan Mary Reynolds Charitable Trust, the Starship Foundation, and the Health Research Council of New Zealand.