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

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

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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Device: MERM-observed self-administered therapy

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ethiopia
  • Addis Ababa, Ethiopia, 9086
    • Addis Ababa University, College of Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MERM-observed self-administered therapy (SAT); 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; 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.; Other Names: EvriMed500 medication event reminder monitor
No Intervention: Standard directly observed therapy (DOT); 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?

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

Collaborators and Investigators

• Sponsor: Addis Ababa University
• Collaborators: Fogarty International Center of the National Institute of Health; Armauer Hansen Research Institute, Ethiopia; Addis Ababa University, College of Health Sciences, CDT-Africa, Ethiopia; Emory University School of Medicine, US
• Investigators: Study Director: Henry M Blumberg, MD, Emory University School of Medicine and Rollins School of Public Health

Publications and helpful links

General Publications

• Manyazewal T, Woldeamanuel Y, Holland DP, Fekadu A, Marconi VC. Effectiveness of a digital medication event reminder and monitor device for patients with tuberculosis (SELFTB): a multicenter randomized controlled trial. BMC Med. 2022 Sep 28;20(1):310. doi: 10.1186/s12916-022-02521-y.
• Manyazewal T, Woldeamanuel Y, Fekadu A, Holland DP, Marconi VC. Effect of Digital Medication Event Reminder and Monitor-Observed Therapy vs Standard Directly Observed Therapy on Health-Related Quality of Life and Catastrophic Costs in Patients With Tuberculosis: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2022 Sep 15;5(9):e2230509. doi: 10.1001/jamanetworkopen.2022.30509.
• Manyazewal T, Woldeamanuel Y, Blumberg HM, Fekadu A, Marconi VC. The potential use of digital health technologies in the African context: a systematic review of evidence from Ethiopia. NPJ Digit Med. 2021 Aug 17;4(1):125. doi: 10.1038/s41746-021-00487-4.
• Manyazewal T, Woldeamanuel Y, Holland DP, Fekadu A, Blumberg HM, Marconi VC. Electronic pillbox-enabled self-administered therapy versus standard directly observed therapy for tuberculosis medication adherence and treatment outcomes in Ethiopia (SELFTB): protocol for a multicenter randomized controlled trial. Trials. 2020 May 5;21(1):383. doi: 10.1186/s13063-020-04324-z.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): July 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: December 27, 2019
• First Submitted That Met QC Criteria: December 30, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 8, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Adherence; Tuberculosis; Ethiopia; Digital health; Medication event reminder monitor; Self-administered therapy; Directly observed therapy (DOT); Treatement outcome
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: 077/19/CDT; D43TW009127 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No