Comparing adherence to MDR-TB treatment among patients on self-administered therapy and those on directly observed therapy: non-inferiority randomized controlled trial

Trials. 2023 May 12;24(1):326. doi: 10.1186/s13063-023-07314-z.

Abstract

Background: Adherence is key to the treatment success of multi-drug resistant tuberculosis (MDR-TB) and prevention of community transmission. Directly observed therapy (DOT) is the recommended approach for the management of patients with MDR-TB. Uganda implements a health facility-based DOT approach where all patients diagnosed with MDR-TB report to the nearest private or public health facility for daily observation of ingesting their medicines by a health care provider. Directly observed therapy is very costly for both the patient and health care system. It follows the assumption that MDR TB patients have a history of poor adherence to TB treatment. But only 21% of MDR-TB patients notified globally and 1.4-12% notified in Uganda had been previously treated for TB. The shift to all oral treatment regimen for MDR-TB provides an opportunity for the exploration of self-administered therapy for this group of patients even with use of remotely operated adherence technology. We are conducting a non-inferiority open-label randomized controlled trial to compare adherence to MDR-TB treatment among patients on self-administered therapy (measured by Medication Events Monitoring System (MEMS) technology) with a control group on DOT.

Methods: We plan to enrol 164 newly diagnosed MDR-TB patients aged ≥ 8 years from three regional hospitals based in rural and urban Uganda. Patients with conditions that affect their dexterity and ability to operate the MEMS-operated medicine equipment will not be eligible to participate in the trial. Patients are randomized to either of the two study arms: self-administered therapy with adherence being monitored using MEMS technology (intervention arm) or health facility-based DOT (control arm) and will be followed up monthly. Adherence is measured by the number of days the medicine bottle is open to access medication as recorded by the MEMS software in the intervention arm and treatment complaint days as recorded in the TB treatment card in the control arm. The primary outcome is the comparison of adherence rates between the two study arms.

Discussion: The evaluation of self-administered therapy for patients with MDR-TB is important to inform cost-effective management strategies for these patients. The approval of all oral regimens for the treatment of MDR-TB provides an opportunity for innovations such as MEMS technology to support sustainable options for MDR-TB treatment adherence support in low-resource settings.

Trial registration: Pan African Clinical Trials Registry, Cochrane #PACTR202205876377808. Retrospectively registered on 13 May 2022.

Keywords: Differentiated care; Directly observed therapy; Medication events monitoring system technology; Multi-drug-resistant tuberculosis; Resource-limited settings; Sub-Saharan Africa; TB drug PK levels; TB treatment adherence; TB treatment outcomes.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antitubercular Agents* / adverse effects
  • Clinical Protocols
  • Directly Observed Therapy
  • Humans
  • Medication Adherence
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant* / diagnosis
  • Tuberculosis, Multidrug-Resistant* / drug therapy

Substances

  • Antitubercular Agents