ADAP-TIV: An Adaptive Randomized Controlled Trial

• Sponsor: Columbia University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05633056
• Collaborator: Centre for the AIDS Programme of Research in South Africa (Other)
• Enrollment: 360
• Location: 1
• Arms: 4
• Anticipated Duration (Months): 48
• Patients Per Site Per Month: 7.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multi Drug Resistant Tuberculosis; HIV Infections	Behavioral: Adherence support intevention	N/A

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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.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)
• Primary Purpose: Supportive Care
• Official Title: 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
• Anticipated Study Start Date: Feb 1, 2023
• Anticipated Primary Completion Date: Feb 1, 2025
• Anticipated Study Completion Date: Feb 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Enhanced standard of care 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 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; Compare the effects of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform.
Other: mHealth 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; Compare the effects of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform.
Other: mHealth and Psychosocial support Combination of Arm 2 and Arm 3.	Behavioral: Adherence support intevention; Compare the effects of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform.

Outcome Measures

Primary Outcome Measures

1. Biological outcome [06 months]

   TB culture conversion

2. Clinical outcome [12 months]

   Survival

3. Biological outcome [12 months]

   HIV viral load

4. Clinical outcome [12 months]

   Retention in care

5. Biological outcome [12 months]

   TB culture conversion

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	King DinuZulu Hospital	Durban	KwaZulu-Natal	South Africa	4001

Sponsors and Collaborators

• Columbia University
• Centre for the AIDS Programme of Research in South Africa

Investigators

• Principal Investigator: Max O'Donnell, Prof, University of Columbia

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form: Informed Consent Form-English - Apr 8, 2022
• Informed Consent Form: English version - Apr 8, 2022

More Information

Additional Information:

• WHO World Health Organization. The end of TB strategy.2015

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• Responsible Party: Max O'Donnell, MD,MPH,Principal investigator, Columbia University
• ClinicalTrials.gov Identifier: NCT05633056
• Other Study ID Numbers: CAP262
• First Posted: Dec 1, 2022
• Last Update Posted: Dec 1, 2022
• Last Verified: Nov 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Tuberculosis; Tuberculosis, Multidrug-Resistant

Study Results

No Results Posted as of Dec 1, 2022