INTRODUCTION: High-quality evidence is crucial for guiding effective humanitarian responses, yet conducting rigorous research, particularly randomised controlled trials, in humanitarian crises remains challenging. The TISA ("traitement intégré de la sous-nutrition aiguë") trial aimed to evaluate the impact of a Water, Sanitation and Hygiene (WASH) intervention on the standard national treatment of uncomplicated Severe Acute Malnutrition (SAM) in children aged 6-59 months. Implemented in two northern Senegalese regions from December 22, 2021, to February 20, 2023, the trial faced numerous challenges, which this paper explores along with the lessons learned. METHODS: The study utilised trial documentation, including field reports, meeting minutes, training plans, operational monitoring data and funding proposals, to retrace the trial timeline, identify challenges and outline implemented solutions. Contributions from all TISA key staff-current and former, field-based and headquarters-were essential for collecting and interpreting information. Challenges were categorised as internal (within the TISA consortium) or external (broader contextual issues). RESULTS: The TISA trial, executed by a consortium of academic, operational, and community stakeholders, enrolled over 2000 children with uncomplicated SAM across 86 treatment posts in a 28,000 km2 area. The control group received standard outpatient SAM care, while the intervention group also received a WASH kit and hygiene promotion. Initially planned to start in April 2019 for 12 months, the trial faced a 30-month delay and was extended to 27 months due to challenges like the COVID-19 pandemic, national strikes, health system integration issues and weather-related disruptions. Internal challenges included logistics, staffing, data management, funding and aligning diverse stakeholder priorities. DISCUSSION AND CONCLUSION: Despite these obstacles, the trial concluded successfully, underscoring the importance of tailored monitoring, open communication, transparency and community involvement. Producing high-quality evidence in humanitarian contexts demands extensive preparation and strong coordination among local and international researchers, practitioners, communities, decision-makers and funders from the study's inception. TRIAL REGISTRATION: Clinicaltrials.gov NCT04667767 .