Background The 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. Methods We 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. Findings From 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. Interpretation The DAT interventions showed no reduction in unfavourable outcomes. This emphasizes the necessity to optimise DATs to enhance TB management strategies and treatment outcomes.

The authors have declared no competing interest.

PACTR202008776694999

This study was funded by Unitaid

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The trial received ethics approval from: the London School of Hygiene & Tropical Medicine Ethics Committee, United Kingdom; WHO Ethical Review Committee, Switzerland and the Addis Ababa City Administration Health Bureau Public Emergency and Health Research Directorate Institutional Review Board, and Oromia Regional Health Bureau Public Emergency and Health Research Directorate Institutional Review Board, Ethiopia.

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