Clinic-based Versus Hotspot-focused Active TB Case Finding

NCT05285202 | Recruiting DMC

• 2 other identifiers: IRB003009392R01HL138728
• Study Type: interventional
• Target: 150,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis, Pulmonary; Mycobacterium Tuberculosis Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• TPT initiations, hotspot vs facility

  From the start to two weeks after the end of each four-month intervention period

• Pulmonary bacteriologically confirmed TB notifications, ACF/TPT vs control

  48 months from start of interventions in each "triplet" of clusters

• Notification trend (intervention vs control) as assessed by Average percent change in number of TB notifications

  First 16 months following start of interventions in a cluster "triplet", versus final 16 months of the interventions (including 4 months of washout after the final intervention) in each triplet

• Study-initiated TB notifications, hotspot vs facility

  From the start to two weeks after the end of each four-month intervention period

• Number screened by study

  During four-month intervention periods (6 periods per cluster over 48 months)

Study Arms (3)

Hotspot-focused ACF/TPT

EXPERIMENTAL

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)

Facility-based ACF/TPT

EXPERIMENTAL

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)

No intervention

NO INTERVENTION

Interventions

Active TB case finding with linkage to preventive therapy (ACF/TPT) OTHER

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).

Facility-based ACF/TPT; Hotspot-focused ACF/TPT

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Johns Hopkins University: lead
• Walimu: collaborator

Study Sites (1)

Walimu

Kampala, Uganda

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Emily Kendall, MD PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily A Kendall, MD PhD

CONTACT

410-502-8234; ekendall@jhmi.edu

David W Dowdy, MD PhD

CONTACT

ddowdy1@jhmi.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: SCREENING
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Twelve clusters or study regions (of which eight will be randomized to receive interventions) will be defined according to the catchment areas of twelve participating Ugandan district hospitals/major health centers. Eight study areas will receive a total of six 4-month intervention periods (alternating between the facility-based and the hotspot focused strategy, for three periods of each type) over a four-year period, with a 4-month wash-out period after each intervention period. Four additional areas will be used as control sites; the only involvement of participants in these sites will be through retrospective collection of de-identified data.

Study Record Dates

• First Submitted: March 9, 2022
• First Posted: March 17, 2022
• Study Start: June 1, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

UG (1)