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

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: Recruiting
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: TB preventive therapy (TPT) - 3 months weekly isoniazid plus rifapentine (3HP)

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 (Estimated): 525
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jason S Caucutt; Phone Number: 12063538069; Email: jcaucutt@uw.edu

Study Locations

• South Africa
  • KwaZulu-Natal
    • Sweetwaters, KwaZulu-Natal, South Africa
      • Recruiting
      • Human Sciences Research Council
      • Contact: Study Coordinator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older
• Meet eligibility criteria for TB preventive therapy by South African national guidelines: is a person living with HIV -or- is a household contact of someone with active TB.
• Screened negative for active TB disease through TB screening activities within 6 months.
• Negative symptom screen at the time of enrollment if TB screening was more than 3 months prior to enrollment.
• Reside in the study community.
• Willing and able to complete informed consent

Exclusion Criteria:

• There are no separate exclusion criteria for adults >=18 years of age.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

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).	Drug: TB preventive therapy (TPT) - 3 months weekly isoniazid plus rifapentine (3HP); Participants randomized to this arm will receive a 2-week 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).	Drug: TB preventive therapy (TPT) - 3 months weekly isoniazid plus rifapentine (3HP); Participants randomized to this arm will receive a 2-week supply of TB preventive therapy (TPT) at enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion of a course of TB preventive therapy (TPT)	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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Human Sciences Research Council
• Investigators: Principal Investigator: Adrienne Shapiro, MD, PhD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2024
• Primary Completion (Estimated): February 10, 2026
• Study Completion (Estimated): December 31, 2026

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 (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Tuberculosis; differentiated service delivery; 3HP; multi-month dispensing; TPT
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Antitubercular Agents; Antibiotics, Antitubercular; Fatty Acid Synthesis Inhibitors; Rifapentine; Isoniazid
• 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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes