Introduction of Dispersible 3HP Formulations for TB Preventive Treatment in Children: a Multi-country Evaluation

The WHO has recommended TB preventive therapy (TPT) for children living with HIV (CLHIV) and household contacts of people living with TB, however, the scale-up and implementation of TPT has been sub-optimal globally particularly in children. A safe and effective short-course TPT regimen, 3HP (rifapentine and isoniazid given once weekly for three months), is available but there is a lack of child-friendly formulations resulting in increased pill burden and there is a need to improve acceptability and adherence among children. The introduction of a dispersible rifapentine formulation has potential to improve uptake, treatment adherence and completion.

Overall goal is to generate critical knowledge to improve delivery of TPT and, more specifically, of dispersible 3HP, in children in routine programs.

This evaluation will create an important understanding of TPT uptake and completion among children and assess the impact of the introduction of a dispersible 3HP formulation. These results will provide actionable information for improving service delivery and the scale-up of TPT in the respective countries.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV; Children, Only; TB - Tuberculosis; Household Contact

• Study Type: Observational
• Enrollment (Estimated): 1200

Contacts and Locations

• Study Contact: Name: Violet Chihota; Phone Number: +27 (0) 82 319 1559; Email: vchihota@auruminstitute.org
• Study Contact Backup: Name: Rachel Mukora; Phone Number: +27 (0) 83 784 3107; Email: rmukora@auruminstitute.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Clinic record review: Routine program data for CLHIV <12 years or children <12 years who are household contacts of people living with TB, who are initiated on TPT.

[A household contact is defined as a person who shared the same enclosed living space with the index patient (someone with infectious TB as defined by country guidelines) for one or more nights or for frequent or extended periods during the day during the 3 months before commencement of the current treatment episode.]

Qualitative study: Policy makers, healthcare workers and parents/caregivers will be interviewed - (>18 years)

Clinic-level assessment: Pharmacy managers/pharmacists, procurement and supply management staff - (>18 years)

Description

Clinic record review

Inclusion Criteria:

• Medical records of children <12 years who are either CLHIV or who are household contacts of people with pulmonary TB and who are initiated on TPT

Exclusion Criteria:

• Records will be excluded for children who are contacts of a drug-resistant, have presumptive TB disease or are currently on TB treatment

Qualitative study

Inclusion Criteria:

• Adult caregiver (>18 years) of a child <12 years of age who is eligible for TPT
• Healthcare worker from one of the clinics in which the study will be conducted who sees outpatient pediatric consultations including TB-exposed children
• Policy maker or program manager who manages or is involved in PMTCT, TB and/or pediatric programming

Exclusion Criteria:

• Any adult caregivers, healthcare workers, policy makers or program managers who are unable or unwilling to provide informed consent for both the interview and audio-recording.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort
Children <12 years who are eligible for TPT - HHC; No intervention. Clinic record review: Data will be retrospectively abstracted from routine medical files using a standardised data collection tool that will document TPT uptake and outcomes
Policy makers/Program managers; No intervention. Qualitative study: We will recruit a purposive sample of policy makers, healthcare workers and caregivers who will be interviewed to evaluate buy-in and explore their insights and experiences on the different TPT regimens and formulations.
Healthcare Workers; No intervention. Qualitative study: We will recruit a purposive sample of policy makers, healthcare workers and caregivers who will be interviewed to evaluate buy-in and explore their insights and experiences on the different TPT regimens and formulations.
Caregivers; No intervention. Qualitative study: We will recruit a purposive sample of policy makers, healthcare workers and caregivers who will be interviewed to evaluate buy-in and explore their insights and experiences on the different TPT regimens and formulations.
Pharmacy managers/pharmacists; No intervention. Clinic assessment: We will assess provider barriers and facilitators to prescribing the new dispersible 3HP (single dispersible formulations of isoniazid and rifapentine) through a survey tool which will collect information on the flow of TPT from national supply to the clinic and dispensing to the child.
Procurement managers/Supply managers; No intervention. Clinic assessment: We will assess provider barriers and facilitators to prescribing the new dispersible 3HP (single dispersible formulations of isoniazid and rifapentine) through a survey tool which will collect information on the flow of TPT from national supply to the clinic and dispensing to the child.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overarching Objective	The overarching goal of the evaluation is to generate critical knowledge to improve delivery of TPT and, more specifically, of dispersible 3HP, in children in routine programs.	18 months
Primary Objective 1	To quantify the TPT care cascade from identification, screening, eligibility, treatment initiation to completion among children <12 years of age, stratified by regimen.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Objective 1	To quantify the prescription of the new dispersible 3HP vs other regimens among children <12 years.	18 months
Secondary Objective 2	To explore policy makers, healthcare workers and caregivers' insights on different regimens and formulations.	18 months
Secondary Objective 3	To assess provider-level barriers and facilitators to delivery of the new dispersible 3HP regimen.	18 months
Secondary Objective 4	To determine the impact of the new dispersible 3HP on supply chain and changes needed to accommodate them.	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Outcome 1	Any uptake of TPT defined as proportion of eligible children who are initiated on TPT, stratified by regimen	18 months
Outcome 2	Proportion of children <12 years initiated on TPT who complete treatment, stratified by regimen.	18 months
Outcome 3	Caregiver experience with and attitudes towards the new dispersible 3HP formulation.	18 months
Outcome 4	Barriers and facilitators of the new dispersible 3HP experienced by healthcare workers and policy makers.	18 months
Outcome 5	Logistics and supply chain issues related to country level procurement, forecasting and distribution to clinic level for the dispersible 3HP.	18 months

Collaborators and Investigators

• Sponsor: The Aurum Institute NPC
• Collaborators: Johns Hopkins University; Clinton Health Access Initiative Inc.; KNCV Tuberculosis Foundation

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 16, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: AUR2-7-428; ERC.0004119 (Other Identifier: World Health Organisation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The evaluation findings will be presented at stakeholder meetings at national level and disseminated to stakeholders and participating sites in each country by means of local meetings. Results will also be written up as conference abstracts and/or journal articles and submitted for publication to an appropriate journal to maximise their dissemination, particularly to clinicians involved in TB programmes.

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.: No