Phone-based screening versus home-based screening after tuberculosis in India (TB Aftermath): a multicentre, open-label, randomised, controlled, non-inferiority trial

BACKGROUND: Tuberculosis survivors and their household contacts are at increased risk for tuberculosis even after treatment completion; however, effective strategies for post-tuberculosis screening remain untested. We aimed to assess whether phone-based screening is non-inferior to home-based screening for tuberculosis after treatment completion in India. METHODS: In this multicentre, open-label, randomised, controlled, non-inferiority trial, we enrolled tuberculosis survivors (aged >18 years) within 60 days of completing treatment for any form of tuberculosis from six public clinics in Maharashtra, India. Household contacts were enumerated at baseline (all ages). Survivors were randomly assigned (1:1) to receive phone-based or home-based symptom screening at 6 months and 12 months. The trial was powered to identify a difference in the tuberculosis detection rate per 100 person-years among survivors and contacts together (primary outcome), comparing screening groups during the 12 months after survivor treatment completion. We conducted an intention-to-treat analysis with a rate difference non-inferiority margin of 1·70 per 100 person-years based on the upper bound of the 95% CI. We adjusted for household-level clustering of tuberculosis by fitting a multilevel Poisson model. We also conducted a subgroup analysis of detection rates among survivors and contacts separately. This study is registered with ClinicalTrials.gov, NCT04333485 and is completed. FINDINGS: We enrolled 1076 tuberculosis survivors (537 in the phone-based screening group and 539 in the home-based screening group) and enumerated 3309 contacts (1638 in the phone-based screening group and 1671 in the home-based screening group) between Jan 21, 2021, and Sept 4, 2023. In the 12-month post-treatment period, tuberculosis was detected in 75 (7%) tuberculosis survivors and 30 (1%) contacts: 41 events in the phone-based screening group (rate 1·19 [95% CI 0·82-1·71]) compared with 64 events in the home-based screening group (1·92 [1·37-2·45]). Non-inferiority was reached (rate difference 0·73 [95% CI 0·05-1·41]). Among tuberculosis survivors, the recurrence detection rate was 4·36 (95% CI 2·87-6·34) in the phone-based screening group compared with 8·00 (5·90-10·60) in the home-based screening group (p=0·01). Among contacts, the tuberculosis detection rate was 0·61 (95% CI 0·32-1·07) in the phone-based screening group compared with 0·70 (0·39-1·20) in the home-based screening group (p=0·70). INTERPRETATION: Risk of tuberculosis remains high for households with a tuberculosis survivor. For detecting tuberculosis among survivors and their household contacts together, phone-based screening was non-inferior to home-based screening. For survivors, the recurrence detection rate was higher in the home-based screening group. Countries with a high burden of recurrence should consider home-based screening among tuberculosis survivors. FUNDING: US National Institute of Allergy and Infectious Diseases.