ThiPhiSA: New Pathways to Prevention From Community TB Screening in South Africa

Not Applicable

Active, not recruiting

• Conditions: Tuberculosis; HIV I Infection

• Registration Number: NCT06214910
• Lead Sponsor: University of Washington

Brief Summary

This study will compare community-delivered, multi-month dispensing of tuberculosis preventive therapy (TPT) to standard-of-care clinic-based TPT delivery in a population of South African adults who are recommended to receive TB preventive therapy.

We hypothesize that persons receiving multi-month dispensing of TPT in the community will have a higher rate of TPT completion at 3 months than persons receiving TPT via standard of care with monthly clinic-based refills.

Detailed Description

The research objective is to understand and overcome key barriers to tuberculosis preventive therapy (TPT) delivery and completion in South Africa in the setting of 3HP scale-up. (3HP: short-course TPT consisting of 3 months weekly isoniazid\[H\] plus rifapentine \[P\]). The study will investigate these factors through a trial comparing community-delivered TPT, to clinic-based TPT and qualitative research investigating barriers to TPT completion and exploring task-shifted TPT delivery.

Aim 1: To determine the effect of community-based initiation and delivery of TPT on TPT completion.

Hypothesis: Community-delivered TPT will be associated with higher initiation and completion of TPT than standard of care clinic-based TPT.

Approach: Persons eligible for TPT will be identified through the Triage+ TB study and other community-based TB screening activities. Eligible persons will be randomized at the household level to 1) Immediate initiation of TPT \& full 12 weeks delivery at once, or 2) Immediate initiation of TPT, 2-week supply, and referral to clinic for TPT completion. TPT adherence and completion will be measured by a combination of self-report, pill count, and serum drug level indicators.

Aim 2: To determine factors associated with TPT initiation and completion in people eligible for TPT identified in community settings.

Hypothesis: People with HIV (PWH) will have better rates of initiation and completion of TPT than people without HIV.

Approach: Participant interviews and surveys at baseline and end-of-study will assess willingness to take TPT, barriers and facilitators for individuals, experience taking TPT, and experience of interactions in clinic settings. Focus groups will be purposively selected based on end-of-study survey responses to elicit factors determining patient experience.

Aim 3: To determine feasibility and acceptability of differentiated service delivery (DSD) approaches, including task-shifting, for TPT delivery and scale-up.

Hypothesis: DSD TPT will be feasible and acceptable. Approach: Participatory qualitative research, and implementation science approaches including workflow mapping will be used to assess clinician-level barriers and inefficiencies in providing clinic-based TPT. In-depth interviews and focus groups will be conducted with pharmacy assistants, nurses, clinic operational managers, and district program managers to assess acceptability. Clinic flow will be mapped to determine effect of task-shifted pharmacy assistant TPT delivery on workflow and patient experience in the clinic.

Study Timeline

• Study First Submitted: 2024-01-08
• Study First Submitted QC: 2024-01-08
• Study First Posted: 2024-01-22
• Study Start: 2024-02-20
• Status Verified: 2025-03
• Last Update Submitted: 2025-07-21
• Last Update Posted: 2025-07-24
• Primary Completion: 2026-02-10
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 540

Inclusion Criteria

• ≥18 years of age
• Living in the study catchment area
• Eligible for TPT according to South African National guidelines(5), i.e. are a) living with HIV or b) are a close contact of a person with TB disease (defined by a person that resides in the same house as a person with TB), c) and in either case
• Have screened negative for TB disease in the last 6 months, through TB TRIAGE+ Trial, other household contact tracing, or other community TB screening
• Negative TB screening at enrolment (if TB TRIAGE+ screening was more than 3 months ago)
• Willing and able to provide written or verbal consent
• Participants whom have not received TPT in the last 12 months; this was confirmed verbally with participants during the enrolment process.

Exclusion Criteria

• Less than 18 years of age.
• Pregnant or planning on pregnancy within next three months
• Planning on moving or relocating from the area within the next three months
• Positive for active TB
• Currently on TB treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Completion of a course of TB preventive therapy (TPT)	3 months, extended to 16 weeks as needed	TPT completion defined as taking 11 doses of 3HP (3 months weekly isoniazid \[H\] plus rifapentine \[P\] ) within 16 weeks of 3HP initiation. The outcome will be measured as a composite outcome including: self-report of doses taken, periodic pill counts, one-time serum drug level of isoniazid.

Secondary Outcome Measures

Name	Time	Method
Overall adherence with TPT	3 months, extended to 16 weeks as needed	Proportion of doses completed
Predictors of TPT adherence	3 months, extended to 16 weeks as needed
Adverse events	3 months, extended to 16 weeks as needed	Assessed by adverse event reporting
Participant satisfaction with the assigned TPT delivery method	3 months, extended to 16 weeks as needed	assessed by questionnaire

Trial Locations

Locations (1)

Human Sciences Research Council; 🇿🇦 Sweetwaters, KwaZulu-Natal, South Africa