Clinic-based Versus Hotspot-focused Active TB Case Finding

Study Overview
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Brief Summary
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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.

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

Conditions
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Tuberculosis, Pulmonary, Mycobacterium Tuberculosis Infection

Intervention / Treatment
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* Other: Active TB case finding with linkage to preventive therapy (ACF/TPT)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hotspot-focused ACF/TPT<br>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)<br>* 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 for eligible for TPT (interested after counseling and either positive tuberculin skin test or known HIV infection).<br>|
| Experimental: Facility-based ACF/TPT<br>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)<br>* 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 for eligible for TPT (interested after counseling and either positive tuberculin skin test or known HIV infection).<br>|
| No Intervention: No intervention<br> | |

What is the study measuring?
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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 | 
| Notification trend (intervention vs control) as assessed by Average percent change in number of TB notifications | Average percent change in number of TB notifications, from the first 16 months of intervention to the final 16 months of intervention, comparing intervention clusters to control clusters. | 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 | 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) |