Pharmacist-led Digital Interventions to Improve Tuberculosis Treatment Adherence (CARE-TB)

Comprehensive Digital Adherence and Remote Engagement to Optimise Treatment Adherence for Tuberculosis Patients (CARE-TB Study) in Selangor, Malaysia: An Effectiveness-Implementation Science Study

The gold standard for tuberculosis (TB) treatment support requires directly observed therapy (DOT), which means a trained health worker observes the patient swallow each dose of medication every day for 2 months. Despite the practice of DOT in Malaysia, 1 in 20 patients are loss-to-follow-up and non-adherent to treatment. Sub-optimal adherence due to poor treatment acceptability and social desirability promotes TB treatment failure, disease relapse, on-going transmission, drug resistance, and death. Telemedicine offers a flexible and less invasive option to support TB treatment adherence. Despite 97% internet and smartphone penetration rates, the practical implementation of digital adherence strategies to support and monitor TB treatment remains untested in Malaysia. The investigators propose to design, implement, and measure the effectiveness of a comprehensive, pharmacist-led digital solution for TB treatment support called CARE-TB which combines a package of asynchronous video-observed therapy, digital reminders, telecounselling and e-learning. In this multi-method effectiveness-implementation (Type 2) study using the Exploration, Preparation, Implementation and Sustainment (EPIS) framework, the investigators aim 1) To identify patient and provider-level facilitators and barriers to CARE-TB adoption via qualitative evaluation and to design a stakeholder-informed implementation strategy, (2) To assess effectiveness of CARE-TB strategy by evaluating (i) implementation outcomes, (ii) patient health outcomes, and (iii) service outcomes, and (3) To evaluate the cost-effectiveness of CARE-TB compared to standard of care from a societal perspective. This study will leverage digital platforms to expand the reach of TB adherence support, enhance adherence to TB treatment and improve treatment completion rates, while utilising existing personnel and resources in among the busiest TB treatment centres in the country.

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis (TB)
• Intervention / Treatment: Behavioral: Standard Care; Behavioral: CARE-TB digital adherence package

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui Moon Koh; Phone Number: +60183926328; Email: kohhuimoon@moh.gov.my
• Study Contact Backup: Name: Reena Rajasuriar; Email: reena@um.edu.my

Study Locations

• Malaysia
  • Selangor
    • Sungai Buloh, Selangor, Malaysia, 47000
      • Recruiting
      • Sungai Buloh Hospital
      • Contact: Nor Arisah Misnan; Phone Number: +60361454333; Email: drnorarisah@moh.gov.my
      • Contact: Farah Syakirah Ahmad; Email: farahsyakirah@moh.gov.my
      • Principal Investigator: Hui Moon Koh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Microbiologically confirmed pulmonary TB (smear- or culture-positive PTB)
2. 18 years old or older
3. Able to give consent and physically able to participate in the study
4. Own a video-recording device with internet connectivity
5. Within the first 3 weeks of intensive phase TB treatment

Exclusion Criteria:

1. Complicated TB disease including TB meningitis, TB bone/joint, and disseminated TB with planned treatment duration of 9 to 12 months.
2. Confirmed or suspected drug-resistant (DR)-TB
3. Documented cognitive, motor, or visual disability that will hinder video device use and lack assistance of a caretaker
4. Receiving injectable anti-TB drugs
5. Incarceration or other involuntary detention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard care arm; Directly observed therapy (healthcare or caretaker-based)	Behavioral: Standard Care; Directly observed therapy at any government healthcare facility (by nurses) or at home (by caretaker); Other Names: Directly observed therapy; In-person dose monitoring
Experimental: CARE-TB arm; CARE-TB package includes pharmacist-led asynchronous video observed therapy, digital medication reminders, telecounselling and e-learning for patients.	Behavioral: CARE-TB digital adherence package; CARE-TB package includes pharmacist-led asynchronous video observed therapy, digital medication reminders, telecounselling and e-learning for patients.; Other Names: education; motivational interviewing; counselling; video observed therapy; reminder; digital intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication adherence (Binary outcome)	Completed ≥ 80% scheduled observations during the 8 weeks following enrolment.	8 weeks following enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence rate (Continuous outcome)	Proportion of doses observed over 8 weeks (Dose observed divided by total observable doses prescribed)	8 weeks following enrolment
Proportion of TB treatment completion, death, loss to follow up, and hospitalization	Proportion of patients completing TB treatment, died, are lost to follow-up or hospitalized during TB treatment	From enrolment till 6 months or treatment completion/ termination
TB cure rate	Proportion of microbiological TB clearance (e.g. AFB smear/ MTB PCR/ MTB culture)	At 6 months of treatment
Adverse event reporting	Number of adverse events or adverse drug reactions reported during TB treatment	From enrolment till 6 months of treatment
EQ-5D-5L Health-related Quality of Life (HRQoL)	HRQoL will be assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. Unit of Measure: EQ-5D index score (range: -0.281 to 1.000 based on country-specific value set) Interpretation: Higher scores indicate better health-related quality of life.	At baseline, 2 months and 6 months of treatment
SF-12 Health-related Quality of Life (HRQoL)	The 12-Item Short Form Survey (SF-12) will be used to assess participants' health-related quality of life. Two summary scores will be generated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The scoring scale is from 0 to 100, the higher the score the better the health related quality of life.	At baseline and 2 months of treatment
Implementation Outcomes: Acceptability, Feasibility, Appropriateness (Quantitative measure)	Implementation outcomes will be assessed using the combined Acceptability of Intervention Measure (AIM), Feasibility of Intervention Measure (FIM), and Intervention Appropriateness Measure (IAM) questionnaire. Unit of Measure: Total and individual mean scores on 5-point Likert scale (1 = completely disagree, 5 = completely agree) Scoring: Each subscale consists of 4 items; subscale scores range from 4 to 20 Interpretation: Higher scores indicate greater perceived acceptability, feasibility, or appropriateness of the intervention	At 2 months and 6 months of treatment
Perceived acceptability, feasibility, and fit of the intervention (Qualitative measure)	Semi-structured qualitative interviews and focus group discussions will explore participants' perceptions of the intervention's acceptability, feasibility, and fit. Unit of Measure: Thematic findings from qualitative analysis Interpretation: Interview data will be thematically coded and analyzed to identify key barriers, facilitators, and contextual factors.	After 6 months of implementation phase
Adoption rate	Rate of uptake (number of participants who agree to use the CARE TB strategy divided by total number offered)	Through study completion, an average of 1 year
Patient fidelity to intervention	Rate of drop-out (count of individuals who fulfill any of the following: withdraw from the study, switch arms, appointment no-show)	8 weeks following enrolment
Healthcare providers (HCP) fidelity to intervention	Rate of reengagement attempt (count of reminders sent to reestablish VOT over total number of missed VOT appointments)	8 weeks following enrolment

Collaborators and Investigators

• Sponsor: University of Malaya
• Investigators: Principal Investigator: Reena Rajasuriar, University of Malaya

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 12, 2025
• First Submitted That Met QC Criteria: July 7, 2025
• First Posted (Actual): July 16, 2025

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: education; pharmacist; tuberculosis; implementation science; monitoring; cost; digital; motivational; video observed therapy; active tuberculosis
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: NMRR ID 23-03504-DLE (IIR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported following deidentification.
• IPD Sharing Time Frame: Beginning 3 months following publication and no end date.
• IPD Sharing Access Criteria: Investigators whose proposed used of data has been approved by independent review. Proposals should be submitted to kohhuimoon@moh.gov.my. To gain access, a data sharing agreement must be signed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

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