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

NCT ID: NCT06214910

Last Updated: 2026-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 301 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-20
• Study Completion Date: 2025-08-04

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.

Conditions

Tuberculosis; HIV I Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

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).

Group Type: OTHER

Community-delivered TB preventive therapy (TPT) - 3 months weekly isoniazid plus rifapentine (3HP)

Intervention Type: OTHER

Participants randomized to this arm will receive the entire supply of TB preventive therapy (TPT) at enrollment.

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).

Group Type: ACTIVE_COMPARATOR

Clinic-link TPT

Intervention Type: OTHER

Participants receive 2-week supply of TPT at initiation, then continue to receive remainder of TPT course at clinic (including refills).

Interventions

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.

Intervention Type: 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).

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Washington

OTHER

Sponsor Role: lead

Human Sciences Research Council

OTHER_GOV

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Responsible Party

Adrienne E Shapiro

Assistant Professor, Global Health

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adrienne E Shapiro, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

Human Sciences Research Council

Sweetwaters, KwaZulu-Natal, South Africa

Countries

South Africa

References

Misra S, Madonsela T, Thomas KK, Grabow C, Lenn M, Morton JF, Reither K, Lynen L, van Heerden A, Essack Z, Bosman S, Shapiro AE. ThiPhiSA: new pathways to TB prevention from community screening - a household-randomised controlled trial in KwaZulu-Natal, South Africa. BMJ Open. 2025 Aug 12;15(8):e100927. doi: 10.1136/bmjopen-2025-100927.

Reference Type: DERIVED

PMID: 40803739 (View on PubMed)

Other Identifiers

1R21AI179276-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00018448

Identifier Type: -

Identifier Source: org_study_id