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

NCT04216420 | Completed DMC

• 2 other identifiers: 077/19/CDTD43TW009127
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis

Keywords

Tuberculosis; Medication event reminder monitor; Self-administered therapy; Directly observed therapy (DOT); Adherence; Treatement outcome; Digital health; Ethiopia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Negative IsoScreen urine isoniazid test

  Two months

• Adverse treatment outcome

  Two months

• Self-reported adherence

  Two months

• Health-related quality of life (HRQoL)

  Two months

• Catastrophic costs

  Two months

Study Arms (2)

MERM-observed self-administered therapy (SAT)

EXPERIMENTAL

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

Standard directly observed therapy (DOT)

NO INTERVENTION

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.

Interventions

MERM-observed self-administered therapy DEVICE

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.

Also known as: EvriMed500 medication event reminder monitor

MERM-observed self-administered therapy (SAT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Addis Ababa University: lead
• Emory University School of Medicine, US: collaborator
• Armauer Hansen Research Institute, Ethiopia: collaborator
• Fogarty International Center of the National Institute of Health: collaborator

Study Sites (1)

Addis Ababa University, College of Health Sciences

Addis Ababa, 9086, Ethiopia

Location

Related Publications (5)

• Manyazewal T, Woldeamanuel Y, Getinet T, Hoover A, Bobosha K, Fuad O, Getahun B, Fekadu A, Holland DP, Marconi VC. Patient-reported usability and satisfaction with electronic medication event reminder and monitor device for tuberculosis: a multicentre, randomised controlled trial. EClinicalMedicine. 2023 Jan 17;56:101820. doi: 10.1016/j.eclinm.2022.101820. eCollection 2023 Feb.

  PMID: 36684395 DERIVED

• 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.

  PMID: 36167528 DERIVED

• 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.

  PMID: 36107429 DERIVED

• 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.

  PMID: 34404895 DERIVED

• 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.

  PMID: 32370774 DERIVED

MeSH Terms

Conditions

Tuberculosis; Directly Observed Therapy

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Medication Adherence; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Study Officials

• Henry M Blumberg, MD

  Emory University School of Medicine and Rollins School of Public Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

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

Study Record Dates

• First Submitted: December 27, 2019
• First Posted: January 2, 2020
• Study Start: June 1, 2020
• Primary Completion: July 31, 2021
• Study Completion: August 31, 2021
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share

Locations

ET (1)