Window Prophylaxis for Mycobacterium tuberculosis Infection Prevention in Child and Adolescent Household Contacts: Study Protocol for a Cluster-Randomized Controlled Trial (the TB-WIN trial)

Trials guidance: The Abstract should not exceed 350 words. Please minimize the use of abbreviations and do not cite references in the abstract. The abstract must include the following separate sections: Background : Mycobacterium tuberculosis acquisition after exposure is common but difficult to diagnose and frequently requires serial testing given that immunological evidence of infection can take several weeks to develop. Even though tuberculosis infection (TBI) is asymptomatic, its long-term effects remain unclear due to poorly understood host-pathogen interactions and delayed disease development, and research has shown that active mycobacterial replication and inflammation occur during TBI. Although the main purpose of antituberculosis prophylaxis has been to prevent people with established TBI from progressing to active tuberculosis disease, a few studies have suggested that this prophylaxis, when administered during the window period after exposure, can prevent the acquisition of TBI in very young children. Considering that newer preventive regimens are shorter and safer, this study aims to assess whether tuberculosis prophylaxis —when given in the window period after exposure— can prevent new infections in older children and adolescents who have been recently exposed. Methods : A multicentre cluster-randomized controlled clinical trial will be performed in Chile. A total of 360 households (clusters) with children aged ≥5 to <18 years, who have been recently exposed to a new case of pulmonary tuberculosis will be randomized to intervention or control arm. In the intervention arm, contacts will receive immediate tuberculosis prophylaxis, regardless of the interferon-gamma release assay (IGRA) result. In the control arm, participants will receive tuberculosis prophylaxis only if the IGRA test results positive, as per standard of care. In both arms, the prophylaxis scheme will be the usual weekly isoniazid plus rifapentine for 12 weeks regimen. The primary outcome will be assessed at the individual level by IGRA conversions from negative at baseline to positive at the 12-week follow-up. Discussion : This trial will establish the effectiveness of a window prophylaxis strategy in reducing the risk of TBI acquisition after exposure in a community setting, a strategy that can potentially contribute to global tuberculosis elimination by reducing M. tuberculosis reservoirs. Trial registration : ClinicalTrials.gov, NCT07086820. Registered 17 July 2025, https://clinicaltrials.gov/study/NCT07086820.