An Adaptive Randomized Controlled Trial (ADAP-TIV)

Columbia University

Status: Enrolling

Conditions: Multi Drug Resistant Tuberculosis; HIV Infections

Treatments: Behavioral: Adherence support intevention

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT05633056

CAP262

AAAT8513

1R01AI167795 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 360 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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360 participants in 4 patient groups

Enhanced standard of care

No Intervention group

Description:

* 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.

Psychosocial support

Other group

Description:

* 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)

Treatment:

Behavioral: Adherence support intevention

mHealth

Other group

Description:

* 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.

Treatment:

Behavioral: Adherence support intevention

mHealth and Psychosocial support

Other group

Description:

Combination of Arm 2 and Arm 3.

Treatment:

Behavioral: Adherence support intevention