An Adaptive Randomized Controlled Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Adaptive Evaluation of mHealth and Conventional Adherence Support Interventions to Optimize Outcome With New Treatment Regimens for Drug-resistant Tuberculosis and HIV in South Africa

Conditions
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Multi Drug Resistant Tuberculosis, HIV Infections

Intervention / Treatment
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* Behavioral: Adherence support intevention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Culture or molecular test positive for MTB Molecular test positive for HIV or a documented HIV positive history Drug-susceptibility testing by molecular (i.e. GeneXpert MTB/RIF) or conventional testing consistent with at least rifampicin-resistant TB, Initiating treatment with a Bedaquiline -containing TB regimen within 4 weeks of enrollment and first-time being treated with BDQ 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, Capacity for informed consent in either isiZulu or English Exclusion Criteria: Pregnancy Prisoners Discretion of IOR or clinician

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An adaptive, randomized controlled trial comparing the effectiveness of 4 adherence support intervention arms. 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Enhanced standard of care<br>Care from trained and supported physicians, nurses, and social workers who have received repeated trainings from study staff on medical and behavioral aspects of DR-TB HIV care, which will be documented in terms of date, attendance, and content All participants who receive care as inpatients will receive an orientation to DR-TB treatment in form of a group session designed to impart key behavioral information and health knowledge about the disease, treatment, and skills to obtain optimal outcome. Discharge counselling session will be conducted prior to discharge. Study participants will complete study assessments at baseline (enrollment) and monthly for the first six months. | |
| Other: Psychosocial support<br>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) | Behavioral: Adherence support intevention<br>* Compare the effects of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform.<br>|
| Other: mHealth<br>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. | Behavioral: Adherence support intevention<br>* Compare the effects of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform.<br>|
| Other: mHealth and Psychosocial support<br>Combination of Arm 2 and Arm 3. | Behavioral: Adherence support intevention<br>* Compare the effects of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biological outcome | TB culture conversion | 06 months | 
| Clinical outcome | Survival | 12 months | 
| Biological outcome | HIV viral load | 12 months | 
| Clinical outcome | Retention in care | 12 months | 
| Biological outcome | TB culture conversion | 12 months |