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The WHO recommends the SAFE strategy for trachoma elimination: Surgery for trichiasis, Antibiotics, Facial cleanliness and Environmental improvement. Multiple rounds of SAFE implementation have proven insufficient to eliminate trachoma in Ethiopia, where over 50% of the global trachoma burden remains. More effective antibiotic treatment schedules and transmission-suppressing approaches are needed. The aim of stronger SAFE is to evaluate the impact of a novel package of interventions to strengthen the A, F and E of SAFE on the prevalence of ocular\n Ct<\/jats:italic>\n and trachoma in Oromia, Ethiopia.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and analysis<\/jats:title>\n 68 clusters were randomised in a 1:1:1:1 ratio to one of (1) standard A\/standard F&E (standard SAFE), (2) standard A\/enhanced F&E, (3) enhanced A\/standard F&E or (4) enhanced A\/enhanced F&E (stronger SAFE). Enhanced A includes two height-based doses of oral azithromycin (equivalent to 20\u2009mg\/kg) given as single doses 2\u2009weeks apart, as mass drug administration, annually. Enhanced F&E includes fly control measures (permethrin-treated headwear and odour-baited traps) and face-washing hygiene behaviour change implemented at household level in selected communities. The interventions will be implemented and reinforced over 3 years.<\/jats:p>\n \n The primary outcome is the prevalence of ocular\n Ct<\/jats:italic>\n by quantitative PCR in children aged 1\u20139 years at 36 months. A key secondary outcome is the prevalence of active (inflammatory) trachoma in the same children, assessed by validated trachoma graders and conjunctival photography. Laboratory technicians and photo-graders are masked to treatment allocation. Other important secondary analyses include process evaluations, assessment of behaviour change, fly indicators, adherence and coverage of interventions and a cost analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Ethics and dissemination<\/jats:title>\n Study protocols have been approved by the National Research Ethics Review Committee of the Ethiopian Ministry of Science and Higher Education and the London School of Hygiene & Tropical Medicine Ethics Committee. An independent data safety and monitoring board oversees the trial. Results will be disseminated through peer-reviewed publications, presentations and reports.<\/jats:p>\n <\/jats:sec>\n \n Trial registration number<\/jats:title>\n \n ISRCTN40760473<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-084478","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:55:18Z","timestamp":1735001718000},"page":"e084478","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Cluster randomised controlled trial of double-dose azithromycin mass drug administration, facial cleanliness and fly control measures for trachoma control in Oromia, Ethiopia: the stronger SAFE trial protocol"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"isrctn40760473","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-9323","authenticated-orcid":false,"given":"Anna 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