Background <p>Late preterm infants (34⁺⁰ to 36⁺⁶&#xa0;weeks’ gestation) account for 7% of births in well-resourced nations. In Aotearoa New Zealand, Māori (Indigenous peoples) make up 20% of late preterm births. Late preterm infants are at higher risk of adverse outcomes, including mortality, cerebral palsy and cognitive impairment. Yet, there has been little focus on prophylactic interventions to address these risks. Late preterm infants have more frequent episodes of intermittent hypoxaemia than term infants in the first few postnatal weeks. Caffeine citrate, a routine intervention for apnoea of prematurity in extremely preterm infants, improves long-term neurodevelopmental outcomes in very low birth weight infants and reduces the incidence of intermittent hypoxaemia in late preterm infants. The Latte Trial aims to determine whether prophylactic caffeine citrate given to late preterm infants from birth to term corrected age improves neurodevelopmental outcomes.</p> Methods <p>This phase III multi-centre, parallel two-arm, double-blind, placebo-controlled randomised superiority trial will randomise 478 late preterm infants or twin pairs to receive caffeine citrate (loading dose 40&#xa0;mg.kg⁻¹, then 20&#xa0;mg.kg⁻¹ daily) or placebo until 40⁺⁰&#xa0;weeks’ postmenstrual age. There is an intentional focus on the recruitment of infants of Māori ethnicity to aspire to Mana Whakamārama (equal explanatory power for the Māori population) given their over-representation in late preterm births. Randomisation will be stratified by centre, gestation at birth (34, 35 or 36 completed weeks) and ethnicity (Māori or non-Māori). The primary outcome is the Bayley Scales of Infant Development 4th Edition cognitive score at 2.5&#xa0;years’ corrected age. Primary analysis will be performed on a modified intention-to-treat basis, comparing outcomes between intervention groups using generalised mixed models with adjustment for stratification, potential confounding by socio-economic status and sex, and non-independence of multiples (random effect).</p> Discussion <p>Of early developmental domains, cognition is the most predictive of later neurodevelopmental outcome and intelligence quotient. Prioritisation of the Indigenous population within trials is important. If prophylactic caffeine citrate is found to improve neurodevelopment in late preterm infants, this could have a significant impact on the long-term quality of life and health and wellbeing of this large population of infants.</p> Trial registration <p>ANZCTR ACTRN12622001344785. Registered on 19 October 2022.</p>