Electronic Pillbox-enabled SAT Versus DOT for TB Medication Adherence and Treatment Outcomes

Study Overview
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Brief Summary
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To address the multifaceted challenges associated with tuberculosis (TB) in-person directly observed therapy (DOT), the World Health Organization recently recommended countries maximize the use of digital adherence technologies. Sub-Saharan Africa needs to investigate the effectiveness of such technologies in local contexts and proactively contribute to global decisions around patient-centered TB care. This study aims to evaluate the effectiveness of pillbox-enabled self-administered therapy (SAT) compared to standard DOT on adherence to TB medication and treatment outcomes in Ethiopia. It also aims to assess the usability, acceptability, and cost-effectiveness (health-related quality of life and catastrophic costs) of the intervention from the patient and provider perspectives. It is designed as a multicenter, randomized, controlled, open-label, non-inferiority, effectiveness-implementation hybrid, mixed-methods, two-arm trial.

Official Title
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Electronic Pillbox-enabled Self-administered Therapy Versus Standard Directly Observed Therapy for Tuberculosis Medication Adherence and Treatment Outcomes in Ethiopia: a Multicenter Randomized Controlled Trial

Conditions
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Tuberculosis

Intervention / Treatment
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* Device: MERM-observed self-administered therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with new or previously treated bacteriologically confirmed drug-sensitive pulmonary TB Eligible to start the standard 6-month first-line anti-TB medication Outpatient Men or women age 18 years and above Able and willing to provide informed consent Exclusion Criteria: Patients with known drug-resistant TB Any condition that causes cognitive impairment such as severe acute illness or injury, developmental retardation, or severe psychiatric illness and thus precludes informed consent or safely participating in the study procedures Inpatients Concurrent extrapulmonary TB Contraindicated medications Active liver disease that requires a TB regimen other than HREZ

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multicenter, randomized, controlled, open-label, non-inferiority, effectiveness-implementation type 2 hybrid trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MERM-observed self-administered therapy (SAT)<br>A participant in the intervention arm (n = 57) will receive a 15-day TB medication supply in the evriMED500 MERM device to self-administer. The participant returns every 15 days, where the healthcare provider counts any remaining tablets in the pillbox device, connects the MERM module with a computer and downloads the pill-taking data, reviews the event reports together with the participant and captures the data, underwent IsoScreen urine isoniazid test and refills the participant with a 15-day medication supply in the MERM device. | Device: MERM-observed self-administered therapy<br>* The MERM device has an electronic module and a medication container that records adherence, stores medication, emits audible and visual on-board alarms to remind patients to take their medications on time and refill, and enables providers to download the data and monitor adherence. It is manufactured by Wisepill Technologies, South Africa.<br>* Other names: EvriMed500 medication event reminder monitor;|
| No Intervention: Standard directly observed therapy (DOT)<br>The provider handles a participant in the control arm (n = 57) according to the standard DOT, where the participant visits the healthcare facility each day throughout the intensive phase to swallow the daily dose with direct observation by the healthcare provider. The participant will undergo the urine isoniazid test every 15 days. Both arms will be treated based on the WHO-recommended two-month fixed-dose-combination of first-line anti-TB drug (2RHZE) delivered as a single daily dose and followed throughout the intensive phase that lasts two months. In the end, participants will undergo a microbiological test to assess sputum smear conversion and trained study staff will complete several data tools, including a treatment outcome monitoring tool, adherence self-report, HRQoL, cost, treatment satisfaction, and MERM usability tools. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of adherence | Individual-level percentage adherence over the two-month intensive phase measured by adherence records compiled from MERM device vs. DOT records. | Two months | 
| Sputum conversion | Participant with sputum smear converted following the standard two-month intensive phase treatment | Before and after the two-month intensive phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative IsoScreen urine isoniazid test | Number of participants with negative IsoScreen urine isoniazid test | Two months | 
| Adverse treatment outcome | Participants having at least one of the three events: treatment not completed; death; or loss to follow-up. | Two months | 
| Self-reported adherence | Participants who self-reported to have forgotten to take their medication | Two months | 
| Health-related quality of life (HRQoL) | The association between MERM-observed therapy and HRQoL, with the HRQoL measured and calculated for each participant by arm using the EuroQoL 5-dimension 5-level (EQ-5D-5L) score ranging from 0 to 1, with a higher score designating better HRQoL. | Two months | 
| Catastrophic costs | Participants with overall TB treatment cost exceeding or equivalent to 20% of their income. | Two months | 
| Post-diagnostic cost from an individual patient's perspective | Participant's cumulative direct costs (out-of-pocket costs related to anti-TB drug pick-up) and indirect costs (guardian and coping costs) over the two-month intensive phase. | Two months | 
| Patient-reported treatment satisfaction | Participant's treatment satisfaction measured using the treatment satisfaction questionnaire for medication version 1.4 (TSQM v1.4) tool on a scale 0 to 100, with higher score indicating better satisfaction. | Two months | 
| Patient-reported usability of the MERM device | Participant's experience using the MERM device measured by an 18-item questionnaire and the score transformed in to a scale from 0 to 100, with higher score indicating better usability (Intervention arm only). | Two months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Medication event reminder monitor, Self-administered therapy, Directly observed therapy (DOT), Adherence, Treatement outcome, Digital health, Ethiopia