Electronic Pillbox-enabled Self-administered Therapy Versus Standard DOT for TB Treatment Adherence and Outcomes

• ClinicalTrials.gov Identifier: NCT04216420
• Recruitment Status: Not yet recruiting
• First Posted: January 2, 2020
• Last Update Posted: January 13, 2020
• Sponsor: Addis Ababa University
• Collaborators: Addis Ababa University, College of Health Sciences; Emory University; Armauer Hansen Research Institute, Ethiopia
• 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: January 13, 2020
• Estimated Study Start Date: February 1, 2020
• Estimated Primary Completion Date: February 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 2, 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) and a self-report on Morisky Medication Adherence Scale (MMAS-8, an 8-item structured, valid tool to measure self-reported medication adherence).
• 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 and drug susceptibility testing (BD BACTEC MGIT 960 TB system, BD Diagnostics, Maryland, US).

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: January 3, 2020)

• Poor treatment outcomes [ Time Frame: Two months ]
  Proportion of patients with poor treatment outcomes (treatment not completed, death, or loss to follow-up) in intervention versus DOT arms.
• Cost-effectiveness: value of health effects [ Time Frame: Two months ]
  Quality-adjusted life years (QALY) of patients in intervention versus DOT arms under EuroQol's EQ-5D-5L quality of life questionnaire, with discount rates of 3% and a score out of 100, where 100 means the best health a patient imagines.
• Cost-effectiveness: individual and societal costs of treatment [ Time Frame: Two months ]
  Proportion of individual and societal costs of treatment when management of adherence followed pillbox-enabled SAT versus DOT.
• Acceptability [ Time Frame: Two months ]
  Proportion of patients in intervention versus DOT arms who perceived satisfaction with their TB treatment when measured on Treatment Satisfaction Questionnaire for Medication scale (TSQM v 1.4, a 14-item valid tool to assess patients' satisfaction with medication across four domains - effectiveness, side effects, convenience, and global satisfaction).
• Usability [ Time Frame: End of two months ]
  Proportion of patients in the intervention arm who perceived the pillbox-enabled SAT as usable (easy to use, benefiting, adherence motivator, reputable) in an interviewer-administered, close-ended questionnaire.
• Behavioral determinants [ 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 determinants [ Time Frame: Two months ]
  Proportion of patients with social determinants (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.

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 Self-administered Therapy Versus Standard DOT for TB Treatment Adherence and 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 problems associated with tuberculosis (TB) in-person directly observed therapy (DOT), the World Health Organization has recently recommended countries to maximize the use of digital adherence technologies. Sub-Saharan Africa needs to early 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) over standard DOT on TB medication adherence and treatment outcomes in Ethiopia. It also aims to assess the usability, cost-effectiveness, and acceptability by patients and healthcare providers of the pillbox-enabled SAT. It is designed as a prospective, multicenter, open-label, randomized, controlled, superiority, mixed-methods trial, supplemented with multiphase optimization strategy (MOST) for interventions on behavioral and social determinants of adherence.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

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

Prospective, multicenter, open-label, randomized, controlled, superiority, mixed-methods trial, supplemented with Multiphase Optimization Strategy (MOST) for interventions on behavioral and social determinants of adherence.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Tuberculosis

Intervention

Device: Electronic pillbox-enabled SAT

It is a 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)
  TB patients in the experimental arm will be dispensed with TB medication supply (HRZE fixed-dose combination therapy) for every 15 days in medication event reminder monitor (MERM) pillbox device (evriMed500 digital medication monitoring and reminder device manufactured by Wisepill Technologies, South Africa) to self-administer throughout the intensive phase
  Intervention: Device: Electronic pillbox-enabled SAT
• No Intervention: Standard directly observed therapy (DOT)
  TB patients in the standard DOT arm will visit the healthcare facility each business day in the intensive (2 months) phase to swallow their daily dose of HRZE with direct observation of the healthcare provider per the standard currently practicing DOT procedure.

• 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: Not yet 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: February 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: No

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
• Emory University
• Armauer Hansen Research Institute, Ethiopia

• Investigators: Not Provided
• PRS Account: Addis Ababa University
• Verification Date: January 2020