Clinical trial NCT05285202: Clinic-based Versus Hotspot-focused Active TB Case Finding
Official title: Clinic Versus Hotspot Active Case Finding and Linkage to Preventive Therapy (ACF/TPT) Strategy Evaluation for TB: A Cluster-Randomized Crossover Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tuberculosis, Pulmonary
Mycobacterium Tuberculosis Infection
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Walimu
First posted: 2022-03-17
Enrollment: 150000
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: SCREENING

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pulmonary bacteriologically confirmed TB notifications, hotspot vs facility
timeFrame: From the start to two weeks after the end of each four-month intervention period
Secondary outcomes:
measure: TPT initiations, hotspot vs facility
timeFrame: From the start to two weeks after the end of each four-month intervention period
measure: Pulmonary bacteriologically confirmed TB notifications, ACF/TPT vs control
timeFrame: 48 months from start of interventions in each "triplet" of clusters
measure: Notification trend (intervention vs control) as assessed by Average percent change in number of TB notifications
timeFrame: 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
measure: Study-initiated TB notifications, hotspot vs facility
timeFrame: From the start to two weeks after the end of each four-month intervention period
measure: Number screened by study
timeFrame: During four-month intervention periods (6 periods per cluster over 48 months)
measure: Number diagnosed by study
timeFrame: During four-month intervention periods (6 periods per cluster over 48 months)
measure: Cost effectiveness (hotspot vs facility) as assessed by cost per disability-adjusted life year averted
timeFrame: From the start to two weeks after the end of each four-month intervention period
measure: Cost effectiveness (ACF/TPT vs no intervention) as assessed by cost per disability-adjusted life year averted
timeFrame: From the start to two weeks after the end of each four-month intervention period
measure: Number evaluated for latent tuberculosis infection (LTBI) with tuberculin skin testing (TST)
timeFrame: During four-month intervention periods (6 periods per cluster over 48 months)
measure: Number referred for TPT
timeFrame: During four-month intervention periods (6 periods per cluster over 48 months)
measure: Contacts screened
timeFrame: During four-month intervention periods (6 periods per cluster over 48 months)
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Walimu
Study officials:
affiliation: Johns Hopkins University
name: Emily Kendall, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: