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.