IntroductionScabies is a significant contributor to global morbidity, affecting approximately 200 million people at any time. Scabies is endemic in many resource-limited tropical settings. Bacterial skin infection (impetigo) frequently complicates scabies infestation in these settings. Community-wide ivermectin-based mass drug administration (MDA) is an effective control strategy for scabies in island settings, with a single round of MDA reducing population prevalence by around 90%. However, current two-dose regimens present a number of barriers to programmatic MDA implementation. We designed the Regimens of Ivermectin for Scabies Elimination (RISE) trial to investigate whether one-dose MDA may be as effective as two-dose MDA in controlling scabies in high-prevalence settings.Methods and analysisRISE is a cluster-randomised non-inferiority trial. The study will be conducted in 20 isolated villages in Western Province of Solomon Islands where population prevalence of scabies is approximately 20%. Villages will be randomly allocated to receive either one dose or two doses of ivermectin-based MDA in a 1:1 ratio. The primary objective of the study is to determine if ivermectin-based MDA with one dose is as effective as MDA with two doses in reducing the prevalence of scabies after 12 months. Secondary objectives include the effect of ivermectin-based MDA on impetigo prevalence after 12 and 24 months, the prevalence of scabies at 24 months after the intervention, the impact on presentation to health facilities with scabies and impetigo, and the safety of one-dose and two-dose MDA.Ethics and disseminationThis trial has been approved by the ethics review committees of the Solomon Islands and the Royal Children's Hospital, Australia. Results will be disseminated in peer-reviewed publications and in meetings with the Solomon Islands Ministry of Health and Medical Services and participating communities.Trial registration detailsAustralian New Zealand Clinical Trials Registry: ACTRN12618001086257. Date registered: 28 June 2018.