Tungu et al. BMC Infectious Diseases (2022) 22:171 https://doi.org/10.1186/s12879-022-07138-3 STUDY PROTOCOL Large-scale (Phase III) evaluation of brofanilide 50WP (VECTRON ™ T500) for indoor residual spraying for malaria vector control in Northeast Tanzania: study protocol for a two-arm, non-inferiority, cluster-randomised community trial Patrick K. Tungu 1,4 , Mark W. Rowland 1* , Louisa A. Messenger 1 , Graham J. Small 2 , John Bradley 1 , Janneke Snetselaar 1,2 , Matthew J. Kirby 1,3 and Njelembo J. Mbewe 1,3 Abstract Background: Indoor residual spraying (IRS) is a major method of malaria vector control across sub-Saharan Africa. Effective control is being undermined by the rapid spread of insecticide resistance. There is major investment in devel- opment of new insecticides for IRS that possess novel modes of action, long residual activity, low mammalian toxicity and minimal cross-resistance. VECTRON ™ T500, a new IRS product containing the active ingredient broflanilide as a 50% wettable powder (WP), has been shown to be efficacious against pyrethroid susceptible and resistant vector spe- cies on mud and concrete substrates in experimental hut (Phase II) trials. Methods: A two-arm non-inferiority cluster randomized controlled trial (Phase III) will be undertaken in Muheza Dis- trict, Tanga Region, Tanzania. VECTRON ™ T500 will be compared to the IRS product Fludora ® Fusion (clothianidin 50% WP + deltamethrin 6.25% WP). The predominant malaria vectors in the study area are pyrethroid-resistant Anopheles gambiae s.s., An. arabiensis and An. funestus s.s. Sixteen village clusters will be pair-matched on baseline vector densi- ties and allocated to reference and intervention arms. Consenting households in the intervention arm will be sprayed with VECTRON ™ T500 and those in the reference arm will be sprayed with Fludora ® Fusion. Each month, CDC light traps will collect mosquitoes to estimate changes in vector density, indoor biting, sporozoite and entomological inoculation rates (EIR). Susceptibility to IRS active ingredients will be assessed using World Health Organisation (WHO) bottle bioassays. Target site and metabolic resistance mechanisms will be characterised among Anopheles field popu- lations from both trial arms. Residual efficacy of both IRS products will be monitored for 12 months post intervention. Questionnaire and focus group discussions will explore factors that influence adherence, adverse effects and benefits of IRS. © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Open Access *Correspondence: mark.rowland@lshtm.ac.uk 1 Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK Full list of author information is available at the end of the article