Cluster-randomized trial of digital adherence technologies and differentiated care to reduce poor end-of-treatment outcomes and recurrence among adults with drug-sensitive pulmonary TB in Ethiopia.

BackgroundThe impact of Digital Adherence Technologies (DATs) on long-term tuberculosis treatment outcomes remains unclear. We aimed to assess the effectiveness of DATs and differentiated care in improving tuberculosis treatment outcomes and recurrence. MethodsWe conducted a pragmatic cluster-randomised trial in Ethiopia. Seventy-eight health facilities (clusters) were randomised to three arms (1:1:1): smart pillbox, medication labels, or standard of care. Adults ([≥]18 years) with drug-sensitive pulmonary tuberculosis on a fixed-dose combination tuberculosis treatment regimen were enrolled and followed-up for 12 months after treatment initiation. Those in the pillbox arm received a pillbox with customisable audio-visual reminders, while participants in the label arm received their TB medication with a weekly unique code label. Opening the box or texting the code prompted real-time dose logging on the adherence platform, facilitating differentiated response by a healthcare worker. The primary outcome comprised death, loss to follow-up, treatment failure, switch to drug-resistant tuberculosis treatment, or recurrence; secondary outcomes included loss to follow-up. Analysis accounted for clustered design with multiple imputation for the primary outcome. The trial is complete and registered with PACTR202008776694999. FindingsFrom 24/05/2021-08/08/2022, 8477 individuals undergoing tuberculosis treatment were assessed for eligibility, and 3885 participants enrolled, of whom 3858 were included in the intention-to-treat population. The median age was 30 years and 41% were female. At 12 months, using multiple imputation, neither the pillbox (adjusted OR 1.04, 95% CI: 0.74-1.45; adjusted risk difference, 1.0 percentage points, 95% CI -1.2 to 3.1) nor the label (adjusted OR 1.14, 95%CI: 0.83-1.61; adjusted risk difference, 0.4 percentage points, 95% CI -1.8 to 2.6) interventions reduced the risk of the primary composite outcome. Results were similar in complete case and per-protocol analyses. InterpretationThe DAT interventions showed no reduction in unfavourable outcomes. This emphasizes the necessity to optimise DATs to enhance TB management strategies and treatment outcomes.