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

Sponsor

Addis Ababa University (Other)

Overall Status

Completed

CT.gov ID

NCT04216420

Collaborator

Addis Ababa University, College of Health Sciences, CDT-Africa, Ethiopia (Other), Emory University School of Medicine, US (Other), Armauer Hansen Research Institute, Ethiopia (Other), Fogarty International Center of the National Institute of Health (NIH)

114

Enrollment

Location

Arms

Actual Duration (Months)

7.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Device: MERM-observed self-administered therapy	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A multicenter, randomized, controlled, open-label, non-inferiority, effectiveness-implementation type 2 hybrid trial.A multicenter, randomized, controlled, open-label, non-inferiority, effectiveness-implementation type 2 hybrid trial.

Masking:

Single (Outcomes Assessor)

Masking Description:

Permuted block randomization method was used to randomly allocate participants and maintain a balance of the number of participants assigned to each arm. The study investigators who were responsible for assessing study outcomes and writing the report were blinded to group allocation until the manuscript was completed. A statistician masked to group allocation performed the analyses.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2020

Actual Primary Completion Date :

Jul 31, 2021

Actual Study Completion Date :

Aug 31, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Negative IsoScreen urine isoniazid test [Two months]
Number of participants with negative IsoScreen urine isoniazid test
Adverse treatment outcome [Two months]
Participants having at least one of the three events: treatment not completed; death; or loss to follow-up.
Self-reported adherence [Two months]
Participants who self-reported to have forgotten to take their medication
Health-related quality of life (HRQoL) [Two months]
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.
Catastrophic costs [Two months]
Participants with overall TB treatment cost exceeding or equivalent to 20% of their income.
Post-diagnostic cost from an individual patient's perspective [Two months]
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.
Patient-reported treatment satisfaction [Two months]
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.
Patient-reported usability of the MERM device [Two months]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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