Clinic-based Versus Hotspot-focused Active TB Case Finding (CHASE-TB)

Clinic Versus Hotspot Active Case Finding and Linkage to Preventive Therapy (ACF/TPT) Strategy Evaluation for TB: A Cluster-Randomized Crossover Trial

This five-year study will evaluate two strategies for conducting tuberculosis (TB) active case finding (ACF) and linkage to TB treatment or TB preventive therapy (TPT) in peri-urban Uganda. The two strategies differ in the location where ACF activities are performed: A "facility-based" ACF/TPT strategy will perform ACF, plus linkage to TPT, in the immediate vicinity of a large public health facility and will primarily recruit individuals who are attending the health facility, irrespective of TB suspicion or symptoms. Alternatively, a "hotspot-based" strategy will use routine notification data and local expertise to identify local TB hotspots - defined as the geographic areas though to have the highest burden of undiagnosed TB per estimated population. The same infrastructure (personnel, equipment, supplies, etc.) for ACF/TPT will then be placed in those zones for a period of four months at a time, and the general population will be recruited for screening and linkage to TPT.

The two interventions will be compared in a Type 1 hybrid effectiveness-implementation trial with a cluster-randomized, multiple-period crossover design. The study will evaluate whether hotspot-focused ACF/TPT results in a greater number of TB patients diagnosed and linked to care, and a greater number of individuals started on preventive therapy, than facility-based ACF/TPT. Secondarily, it will also compare the two interventions in terms of number of people initiated on TPT, and it will compare TB cases detected in regions performing ACF/TPT (either approach) against cases detected in regions that continue to perform the standard of care.

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis, Pulmonary; Mycobacterium Tuberculosis Infection
• Intervention / Treatment: Other: Active TB case finding with linkage to preventive therapy (ACF/TPT)

• Study Type: Interventional
• Enrollment (Estimated): 150000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emily A Kendall, MD PhD; Phone Number: 410-502-8234; Email: ekendall@jhmi.edu
• Study Contact Backup: Name: David W Dowdy, MD PhD; Email: ddowdy1@jhmi.edu

Study Locations

• Uganda
  • Kampala, Uganda
    • Recruiting
    • Walimu
    • Principal Investigator: Achilles Katamba, MBChB PhD
    • Contact: Achilles Katamba; Phone Number: 256-414-530-021,; Email: amkatamba@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≥15 years, OR age 5-14 and a close contact of someone diagnosed with TB,
• Provision of oral informed consent, or, if age <18 years and not legally emancipated, oral informed assent (if ages 8-17) and parental informed consent (ages 5-17) to participate in the study
• Ability to communicate with study staff in English or Luganda, or availability of a capable interpreter who is acceptable to the participant

Exclusion Criteria:

• On treatment for, or diagnosed with but not yet treated for, active TB

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No intervention
Experimental: Hotspot-focused ACF/TPT; ACF/TPT intervention will be delivered in a community setting, in geographic areas judged likely to have a high burden of undiagnosed TB	Other: Active TB case finding with linkage to preventive therapy (ACF/TPT); ACF/TPT in both intervention arms will consist of TB screening by mobile chest X-ray (with artificial intelligence-based reading, followed by confirmatory sputum testing with Xpert MTB/RIF Ultra for participants with abnormal x-rays), and linkage to preventive therapy for those who are TB-negative and eligible for TPT (limited in April 2024 to those with close TB contact or known HIV infection).
Experimental: Facility-based ACF/TPT; ACF/TPT intervention will be delivered on the grounds of a health facility (hospital or large public health center)	Other: Active TB case finding with linkage to preventive therapy (ACF/TPT); ACF/TPT in both intervention arms will consist of TB screening by mobile chest X-ray (with artificial intelligence-based reading, followed by confirmatory sputum testing with Xpert MTB/RIF Ultra for participants with abnormal x-rays), and linkage to preventive therapy for those who are TB-negative and eligible for TPT (limited in April 2024 to those with close TB contact or known HIV infection).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary bacteriologically confirmed TB notifications, hotspot vs facility	Number of study region residents notified as initiating treatment for bacteriologically confirmed new or relapsed pulmonary TB, comparing periods in which regions performed hotspot-focused ACF/TPT to those in which facility-based ACF/TPT was performed.	From the start to two weeks after the end of each four-month intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TPT initiations, hotspot vs facility	Number of study region residents initiating TPT during intervention periods, comparing periods in which regions performed hotspot-focused ACF/TPT to those in which facility-based ACF/TPT was performed.	From the start to two weeks after the end of each four-month intervention period
Pulmonary bacteriologically confirmed TB notifications, ACF/TPT vs control	Number of study region residents notified as initiating treatment for bacteriologically confirmed new or relapsed pulmonary TB, comparing intervention regions to control regions.	48 months from start of interventions in each "triplet" of clusters
Study-initiated TB notifications, hotspot vs facility	Number of people diagnosed with TB through study participation and initiating treatment for TB, hotspot-focused and facility-based ACF/TPT.	From the start to two weeks after the end of each four-month intervention period
Number screened by study	Total number of people screened for TB with each intervention.	During four-month intervention periods (6 periods per cluster over 48 months)
Number diagnosed by study	Number of study participants found to have Xpert-positive sputum.	During four-month intervention periods (6 periods per cluster over 48 months)
Cost effectiveness (hotspot vs facility) as assessed by cost per disability-adjusted life year averted	Incremental cost per disability-adjusted life year (DALY) averted, comparing the more to the less effective ACF/TPT intervention (if an effectiveness difference is found).	From the start to two weeks after the end of each four-month intervention period
Cost effectiveness (ACF/TPT vs no intervention) as assessed by cost per disability-adjusted life year averted	Incremental cost per disability-adjusted life year (DALY) averted, comparing ACF/TPT to no ACF/TPT.	From the start to two weeks after the end of each four-month intervention period
Number evaluated for latent tuberculosis infection (LTBI) with tuberculin skin testing (TST)	Total number of people completing TST placement and reading by the study	During four-month intervention periods (6 periods per cluster over 48 months)
Number referred for TPT	Number of participants referred for TB preventive therapy based on TST result or other eligibility criteria	During four-month intervention periods (6 periods per cluster over 48 months)
Contacts screened	Number of people screened for TB who are identified as contacts of a person diagnosed with TB through the study	During four-month intervention periods (6 periods per cluster over 48 months)
TB notification trend (intervention vs control)	Trend in TB notification rate over the span of study intervention involvement, comparing intervention clusters to control clusters	Approximately 38 to 46 months per cluster (5 to 6 four-month intervention periods, plus intervening washout periods)

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Walimu
• Investigators: Principal Investigator: Emily Kendall, MD PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: March 9, 2022
• First Submitted That Met QC Criteria: March 9, 2022
• First Posted (Actual): March 17, 2022

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: IRB00300939; 2R01HL138728 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data that underlie results in publications
• IPD Sharing Time Frame: deposited at the time of publication and available indefinitely
• IPD Sharing Access Criteria: will be deposited into a controlled access data repository and made available for approved noncommercial research
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No