Choice Architecture Based TB Preventive Therapy Prescribing

NCT04466293 | Completed

• 1 other identifier: IRB00227388
• Study Type: interventional
• Target: 57
• Locations: 3 countries
• Sites: 3

Brief Summary

Background: Clinical guidelines and policies often fail to achieve high levels of delivery of intended clinical interventions. The difference in what investigators know works and what is actually delivered at the clinic-level to patients, is known as the "science-to-service gap." In the realm of tuberculosis (TB) prevention, this gap is reflected in \<20% of TB preventive therapy (TPT)-eligible persons living with HIV (PLWH) being offered or initiated on isoniazid preventive therapy (IPT) in many settings. Recent innovation in TPT have brought new pharmacological options allowing for shorter courses, intermittent dosing, or both. A 12-dose once-weekly rifapentine and isoniazid (3HP) regimen has been demonstrated to be effective and well tolerated. This regimen has several potential advantages over IPT; however, if patients are never assessed for 3HP eligibility and 3HP is not prescribed, TPT packets will remain on pharmacy shelves and the potential health benefits will not reach those who need it. The overarching goal of this study is to identify a generalizable approach to overcome current barriers to delivery of TPT in order to achieve high levels of TPT delivery during routine care in public clinics. Investigators are proposing a choice architecture that makes prescribing TPT the "default" or standard option and that for TPT not to be prescribed will require a choice by a clinician to "opt-out" of TPT for a specific patient. Methods: Investigators will use a cluster randomized design with the larger IMPAACT4TB (I4TB) program to deliver 3HP to countries in Africa, Asia, and Latin America. A subset of countries and clinics within these I4TB countries will be included with each clinic the unit of randomization. Clinics within study countries will be randomized to one of two strategies: (1) standard implementation within the UNITAID project (clinic training on TPT along with posters and other standard medication material) and (2) choice architecture default TPT. Clinical process data will be used to assess the effectiveness of each strategy to determine the proportion of PLWH (1) screened for TB preventive therapy, (2) eligible for TPT, and (3) prescribed TPT. Significance: Identifying a pragmatic approach will lead the way for improving TPT prescribing across the study sites. It will furthermore contribute to implementation science at large in describing implementation strategies that may be applied to clinic-level implementation of other innovations.

Conditions

HIV/AIDS; Tuberculosis

Keywords

TB; Preventive; Therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of PWH initiating ART who are prescribed 3HP (or IPT)

  Among those eligible/estimate of those eligible or the total ART initiator population

  Up to 12 months

Secondary Outcomes (10)

• Proportion of established ART patients who are prescribed 3HP or IPT

  Up to 12 months

• Proportion of all unique HIV patients during study period prescribed 3HP or IPT

  Up to 12 months

• Proportion completing TPT among those initiating 3HP or IPT

  Up to 12 months

• Adverse events among TPT recipients and non-TPT recipients

  Monthly or quarterly (dependent on country-level routine reporting) over a 12 month period

• Number of TB cases diagnosed among individuals on TPT

  Up to 12 months

Study Arms (2)

Standard of care study arm

NO INTERVENTION

Providers will receive training on benefits, indications, and contra-indications for TPT. Providers will use the standard approach of the "default" being to not prescribe. Only if providers specifically write for TPT will it be dispensed by a pharmacy or the provider.

Choice Architecture study arm

EXPERIMENTAL

Clinic staff will be responsible for strategy delivery for all patient interactions. Research staff will provide training and guidance for the "choice architecture" arm. Research staff will also work with the clinics to develop appropriate clinical stationary, ink stamps, stickers, or EMR modifications for prescribing, and reminder systems (e.g. written by pharmacy in clinic file, post-it on clinic file, post-it on lab results). The goal of this approach is for TPT prescribing to occur routinely and as part of ART prescribing. This is in contrast to considering prescribing only at the end of a long algorithm that includes TB and other assessments. With this approach, a patient will "automatically" be prescribed TPT unless the clinician specifically decides patients are not candidates due to active TB treatment or other clinical reasons.

Behavioral: Choice Architecture

Interventions

Choice Architecture BEHAVIORAL

1. Providers will receive general training on TPT benefits, indications, and contra-indications. 2. Providers will be provided with updated ART and TPT prescribing approach. This will be adapted to the country context and may include a pre-printed prescription pad (Mozambique), adaptations in clinical stationary (Zimbabwe), or adaptations to an electronic prescribing system (Malawi). 3. The pharmacy or clinician (if the clinician dispenses) will dispense ART, cotrimoxazole, and TPT as prescribed

Choice Architecture study arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• As this is a health system strategy with the intervention at the clinic level, all adult PWH receiving care at that clinic will be exposed to the strategy and included in the overall proportion of PWH seen at the clinic during the study period who receive 3HP

You may not qualify if:

• None

Sponsors & Collaborators

• Johns Hopkins University: lead
• KNCV Tuberculosis Foundation: collaborator
• Clinton Health Access Initiative, Zimbabwe: collaborator
• Aurum Institute: collaborator

Study Sites (3)

KNCV Tuberculosis Foundation

Lilongwe, Malawi

Location

Aurum Institute

Maputo, Mozambique

Location

Clinton Health Access Initiative

Harare, Zimbabwe

Location

Related Publications (1)

• Shearer K, Nonyane BAS, Mulder C, Kaonga E, Nyirenda R, Mbendera K, Sambani C, Valverde E, Manguambe S, Chiau R, Kawaza N, Jokwiro J, Dube B, Apollo T, Weiser J, Chihota V, Churchyard GJ, Chaisson RE, Golub JE, Hoffmann CJ. An evaluation of a choice architecture-based intervention on prescribing of TB preventive treatment to people living with HIV in southern Africa (the CAT study): a cluster-randomised trial. BMJ Glob Health. 2025 May 24;10(5):e016921. doi: 10.1136/bmjgh-2024-016921.

  PMID: 40412816 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Tuberculosis

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• Christopher Hoffmann, MD, MPH

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Jonathan Golub, PhD, MPH

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The data identified by clinic allocation will be blinded to the PI and co-investigators and study statistician until completion of comparative analysis. There will be no other blinding.
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Clinic randomization to study arm will be conducted publically (either in a single location, or if blocking by country, in each country). Randomization will be achieved either through computer randomization or through drawing marked balls from a bag. Randomization will be stratified by country and within each country by clinic ART population and urban / rural location. The enrolled number reflects clinics participating in the study rather than individual participants because the study did not enroll individual participants in the trial.

Study Record Dates

• First Submitted: July 7, 2020
• First Posted: July 10, 2020
• Study Start: March 29, 2021
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: One year after completion of study activities
• Access Criteria: Contact PI

Locations

ZI (1); MO (1); MA (1)