Digital adherence technology interventions to reduce poor end-of-treatment outcomes and recurrence among adults with drug-sensitive tuberculosis in Ethiopia: a three-arm, pragmatic, cluster-randomised, controlled trial

Background The effect of digital adherence technologies (DATs) on long-term tuberculosis treatment outcomes remains unclear. We aimed to assess the effectiveness of DATs in improving tuberculosis treatment outcomes and recurrence. Methods We did a pragmatic cluster-randomised trial in Ethiopia. 78 health facilities (clusters) were randomised (1:1:1) to smart pillbox, medication labels, or standard of care. Adults aged 18 years or older 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 smart pillbox group received a pillbox with customisable audio-visual reminders, whereas participants in the medications label group received their tuberculosis 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 to an individual's adherence by a health-care worker. The primary composite outcome comprised death, loss to follow-up, treatment failure, switch to drug-resistant tuberculosis treatment, or recurrence. Secondary outcomes were poor end-of-treatment outcome and loss to follow-up. Analysis accounted for clustered design with multiple imputation for the primary composite outcome. The trial is registered with Pan African Clinical Trials Registry (PACTR202008776694999) and is complete. Findings From May 24, 2021, to Aug 8, 2022, 8477 individuals undergoing tuberculosis treatment were assessed for eligibility. Of the 3885 participants enrolled, 3858 were included in the intention-to-treat population. 1567 (40·6%) of 3858 participants were women and the median age of all participants was 30 years (IQR 24-40). At 12 months, using multiple imputation, neither the smart pillbox group (adjusted odds ratio [OR] 1·04 [95% CI 0·74 to 1·45]; adjusted risk difference: 0·96 percentage points [95% CI -1·19 to 3·11]) nor the medication labels group (adjusted OR 1·14 [0·83 to 1·61]; adjusted risk difference: 0·42 percentage points [-1·75 to 2·59]) reduced the risk of the primary composite outcome. There was no evidence of effect on poor end-of-treatment outcomes or loss to follow-up in either intervention group, although the label intervention showed weak evidence of reduced loss to follow-up. Results were similar in complete case and per-protocol analyses. Interpretation The DAT interventions showed no reduction in unfavourable outcomes. This emphasises the necessity to optimise DATs to enhance tuberculosis management strategies and treatment outcomes. Funding Unitaid.