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

• ClinicalTrials.gov Identifier: NCT04216420
• Recruitment Status: Recruiting
• First Posted: January 2, 2020
• Last Update Posted: December 2, 2020
• Sponsor: Addis Ababa University
• Collaborators: Addis Ababa University, College of Health Sciences, CDT-Africa, Ethiopia; Emory University School of Medicine, US; Armauer Hansen Research Institute, Ethiopia; John E. Fogarty International Center, US
• Information provided by (Responsible Party): Dr. Tsegahun Manyazewal, Addis Ababa University

Tracking Information

• First Submitted Date: December 27, 2019
• First Posted Date: January 2, 2020
• Last Update Posted Date: December 2, 2020
• Actual Study Start Date: June 1, 2020
• Estimated Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2020)

• Level of adherence [ Time Frame: Two months ]
  Proportion of patients who missed doses in intervention (pill count) versus DOT (direct observation) arms, confirmed further by urine isoniazid test (IsoScreen test, GFC Diagnostics Ltd, Bicester, England).
• Sputum conversion [ Time Frame: Before and after the two-month intensive phase ]
  Proportion of patients with smear conversion following the intensive phase in intervention versus DOT arms, confirmed further by pre-post intensive phase TB liquid culture (BD BACTEC MGIT 960 TB system, BD Diagnostics, Maryland, US). Pre-post treatment drug susceptibility testing will determine whether resistance to anti-TB drugs could have impacted culture conversion.

Original Primary Outcome Measures (submitted: December 30, 2019)

• Medication adherence [ Time Frame: Two months ]
  Proportion of patients who missed doses in intervention (pill count) versus DOT (direct observation) arms, confirmed further by urine isoniazid test (IsoScreen test, GFC Diagnostics Ltd, Bicester, England)
• Treatment outcomes [ Time Frame: Two months ]
  Proportion of patients' with smear conversion following intensive phase in intervention versus DOT arms, confirmed further by TB liquid culture and drug susceptibility testing (BD BACTEC MGIT 960 TB system, BD Diagnostics, Maryland, US)

Current Secondary Outcome Measures (submitted: November 30, 2020)

• Adverse treatment outcomes [ Time Frame: Two months ]
  proportion of participants in each arm having one of the following events: treatment not completed; death; or loss to follow-up
• Cost-effectiveness: value of health effects [ Time Frame: Two months ]
  Quality-adjusted life years (QALYs) will be calculated for each participant by arm using the EuroQol's EQ-5D-5 L quality-of-life questionnaire, with discount rates of 3% and a score out of 100, with 100 defining optimal health.
• Cost-effectiveness: individual and societal costs of treatment [ Time Frame: Two months ]
  Individual and societal costs of treatment will be calculated for each participant using the Tool to Estimate Patients' costs developed jointly by KNCV Tuberculosis Foundation, WHO, and the Japan Anti-Tuberculosis Association.
• Acceptability [ Time Frame: Two months ]
  Proportion of participants in intervention versus DOT arms who perceived satisfaction with their TB treatment when measured on the Treatment Satisfaction Questionnaire for Medication scale (TSQM v 1.4, a 14-item valid tool to assess participants' satisfaction with medication across four domains: effectiveness; side effects; convenience; and global satisfaction).
• Usability [ Time Frame: End of two months ]
  Usability will be calculated as the proportion of participants in the intervention arm who perceived the evriMED500 device as usable under adopted System Usability Scale (SUS, a 18-item valid tool to assess user performance of the device in six dimensions: ease of use; challenges; benefits; perceptions of being motivated; popularity; and recommendations)

Original Secondary Outcome Measures (submitted: December 30, 2019)

• Usability [ Time Frame: Two months ]
  Proportion of patients in the intervention arm who evaluated the pillbox as usable on System Usability Scale (SUS)
• Cost-effectiveness [ Time Frame: Two months ]
  Quality-adjusted life year (QALY) in intervention versus DOT arms
• Acceptability [ Time Frame: Two months ]
  Treatment satisfaction of patients on a Treatment Satisfaction Questionnaire for Medication (TSQM v 1.4) scale in intervention versus DOT arms
• Behavioral factors [ Time Frame: Two months ]
  Proportion of patients with behavioral factors (use cigarettes, alcohol, chat, cocaine/marijuana) that had adherence problems in the first month of their treatment but improved following additional interventions using Multiphase Optimization Strategy (MOST): i) behavioral intervention, ii) behavioral plus reducing refill schedules to one week (from two weeks), and iii) reassigning to DOT.
• Social factors [ Time Frame: Two months ]
  Proportion of patients with social factors (homeless, unemployed, illiterate) that had adherence problems in the first month of treatment but improved following further interventions using MOST i) behavioral intervention, ii) behavioral plus reducing refill schedules to one week (from two weeks), and iii) reassigning to DOT.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Electronic Pillbox-enabled SAT Versus DOT for TB Medication Adherence and Treatment Outcomes
• 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
• 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 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

a multicenter, randomized, controlled, open-label, superiority, effectiveness-implementation hybrid, mixed-methods, two-arm trial.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Tuberculosis

Intervention

Device: Electronic pillbox-enabled SAT

It is a digital device manufactured by Wisepill Technologies, South Africa. Every time a pill dispenser is opened, the evriMED500 stores the date and time of the opening. Adherence data and reports can be viewed on the Wisepill Cloud Server and on the mobile-friendly browser application.

Other Name: EvriMed500 medication monitoring and reminder system

Study Arms

• Experimental: Electronic pillbox-enabled self-administered therapy (SAT)
  Participants in the intervention arm (n = 72) will receive 15 days of HRZE-isoniazid, rifampicin, pyrazinamide, and ethambutol-fixed-dose combination therapy in the evriMED500 medication event reminder monitor device (Wisepill Technologies, South Africa) for self-administration. When returned, providers will count any remaining tablets in the device, download the pill-taking data, and refill based on preset criteria. Participants can consult the provider in cases of illness or adverse events outside of scheduled visits.
  Intervention: Device: Electronic pillbox-enabled SAT
• No Intervention: Standard directly observed therapy (DOT)
  Providers handle participants in the control arm (n = 72) according to the standard DOT.

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 30, 2019): 144
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2021
• Estimated Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 to 75 years
• 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
• Expected to move away from the study site before the final study follow up at month two
• Concurrent extrapulmonary TB
• Contraindicated medications
• Active liver disease that requires a TB regimen other than HREZ

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Tsegahun Manyazewal, PhD; 118961396 ext +251; tsegahunm@gmail.com

Contact: Yimtubezinash Woldeamanuel, MD, PhD; 118961396 ext +251; yimtubezenash.wamanuel@aau.edu.et

• Listed Location Countries: Ethiopia

Administrative Information

• NCT Number: NCT04216420
• Other Study ID Numbers: 077/19/CDT; D43TW009127 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Dr. Tsegahun Manyazewal, Addis Ababa University
• Study Sponsor: Addis Ababa University

Collaborators

• Addis Ababa University, College of Health Sciences, CDT-Africa, Ethiopia
• Emory University School of Medicine, US
• Armauer Hansen Research Institute, Ethiopia
• John E. Fogarty International Center, US

Investigators

• Study Director: Henry M Blumberg, MD; Emory University School of Medicine and Rollins School of Public Health

• PRS Account: Addis Ababa University
• Verification Date: November 2020