An Adaptive Randomized Controlled Trial

Not Applicable

Recruiting

• Conditions: HIV Infections; Multi Drug Resistant Tuberculosis
• Interventions: Behavioral: Adherence support intevention

• Registration Number: NCT05633056
• Lead Sponsor: Columbia University

Brief Summary

This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of 4 intervention arms on a combined endpoint in adults with confirmed MDR-TB HIV initiating Bedaquiline-containing MDR-TB treatment regimens and on ART (integrase strand transfer inhibitor (INSTI)-based fixed dose combination therapy) in KwaZulu-Natal, South Africa. Interventions arms include: enhanced standard of care; psychosocial support; mHealth using cellular-enabled electronic dose monitoring; combined mHealth psychosocial support. Level of support will be adjusted using a differentiated service delivery (DSD)- informed assessment of treatment support needs.

Detailed Description

This study will follow a 4-arm Bayesian, adaptive trial design. As patients are enrolled, they will be randomized into one of the four arms.

The study will be carried out within a common structure to allow for efficient enrollment and analysis. The overall structure is a 4-arm adaptive platform of mHealth and psychosocial adherence support interventions informed by a differentiated service delivery (DSD) approach.

Aim 1 is an adaptive study of mHealth and psychosocial adherence support interventions using a Bayesian adaptive design to allow comparison of elements of the intervention separately and in combination. Aim 1 participants will be randomized into one of 4 arms and followed monthly through the 6 months of intervention, then through the end of treatment telephonically, with an additional in-person visit to establish the primary outcome. Primary outcome is a combined clinical/biological outcome at 12 months described below. Hypothesis 1a utilizes all participants while 1b utilizes only those in the mHealth intervention arms (3+4) since granular EDM-measured adherence is required.

Study Timeline

• Study First Submitted: 2022-11-21
• Study First Submitted QC: 2022-11-21
• Study First Posted: 2022-12-01
• Study Start: 2023-03-07
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-04
• Primary Completion: 2027-04
• Study Completion: 2029-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

1. Culture or molecular test positive for MTB
2. Molecular test positive for HIV or a documented HIV positive history
3. Drug-susceptibility testing by molecular (i.e. GeneXpert MTB/RIF) or conventional testing consistent with at least rifampicin-resistant TB,
4. Initiating treatment with a Bedaquiline -containing TB regimen within 4 weeks of enrollment and first-time being treated with BDQ
5. On treatment with Antiretroviral Therapy (ART) regimen, including dolutegravir-containing combination Antiretroviral Therapy regimen (i.e. Tenofovir-Lamivudine-Dolutergravir), or starting within 4 weeks of enrollment,
6. Capacity for informed consent in either isiZulu or English

Exclusion Criteria

1. Pregnancy
2. Prisoners
3. Discretion of IOR or clinician

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Psychosocial support	Adherence support intevention	* In addition to Arm 1 * Participants will participate in individual counseling aligned with their monthly clinic visit. * Individual counseling will use motivational interviewing (MI) techniques, based on the 4-part engaging, focusing, evoking and planning approach for each participant. * Home visits will be conducted (if warranted/consented for by the participant) by the same trained counselors known to patients. * Adherence support groups will be facilitated by counselors trained in group facilitation methods; group curriculum will include 6 sessions (monthly, gender specific, structured adherence support groups) that focus on practical topics. * Discharge planning (if inpatient) * Community treatment planning (if outpatient)
mHealth and Psychosocial support	Adherence support intevention	Combination of Arm 2 and Arm 3.
mHealth	Adherence support intevention	* In addition to Arm 1 * Participants will receive x 2 portable Wisepill devices. (x1 for MDR-TB treatment and x1 for ART). A Wisepill device is an RT2000 cellular-enabled electronic pill boxes using 2G/3G cellular network. * Participants will select a text message reminder from a guided menu of choices and receive a weekly text message encouraging adherence. * Participants will receive a study call to support regular adherence. Participants will be assessed weekly. Less than 85% observed/expected doses will be considered at risk for non-adherence and the intervention will be increased.

Primary Outcome Measures

Name	Time	Method
Clinical outcome	12 months	Retention in care
Biological outcome	12 months	TB culture conversion

Trial Locations

Locations (1)

King DinuZulu Hospital; 🇿🇦 Durban, KwaZulu-Natal, South Africa