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

December 30, 2025 updated by: Adrienne E Shapiro, University of Washington

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

301

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • KwaZulu-Natal
      • Sweetwaters, KwaZulu-Natal, South Africa
        • Human Sciences Research Council

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Investigational: Community-based TB preventive therapy (TPT)
Participants in the community arm will receive a multi-month dispensing packet at enrollment with the complete 3 month supply of TPT (3HP: 3 months of weekly isoniazid and rifapentine).
Other: Community-delivered TB preventive therapy (TPT) - 3 months weekly isoniazid plus rifapentine (3HP)
Participants randomized to this arm will receive the entire supply of TB preventive therapy (TPT) at enrollment.
Active Comparator: Standard-of-Care Tuberculosis Preventative Therapy (TPT)
Participants in the standard of care arm will receive a referral letter to their local Department of Health (DoH) clinic to continue TPT. They will be instructed to present to the DoH clinic within 2 weeks to receive their continuation doses of TPT per current South African DoH standard of care (refills administered monthly).
Other: Clinic-link TPT
Participants receive 2-week supply of TPT at initiation, then continue to receive remainder of TPT course at clinic (including refills).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Completion of a course of TB preventive therapy (TPT)
Time Frame: 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.
3 months, extended to 16 weeks as needed

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Human Sciences Research Council

Investigators

  • Principal Investigator: Adrienne E Shapiro, MD, PhD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2024

Primary Completion (Actual)

May 30, 2025

Study Completion (Actual)

August 4, 2025

Study Registration Dates

First Submitted

January 8, 2024

First Submitted That Met QC Criteria

January 8, 2024

First Posted (Actual)

January 22, 2024

Study Record Updates

Last Update Posted (Estimated)

January 2, 2026

Last Update Submitted That Met QC Criteria

December 30, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00018448
  • 1R21AI179276-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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