Clinic-based Versus Hotspot-focused Active TB Case Finding

Tuberculosis, Pulmonary Clinical Trial

— CHASE-TB  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05285202
• Other study ID #: IRB00300939
• Secondary ID: 2R01HL138728
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2022
• Est. completion date: January 31, 2027

Study information

• Verified date: April 2024
• Source: Johns Hopkins University
• Contact: Emily A Kendall, MD PhD
• Phone: 410-502-8234
• Email: ekendall[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80000
• Est. completion date: January 31, 2027
• Est. primary completion date: January 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Latent Tuberculosis
• Mycobacterium Tuberculosis Infection
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

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).

Locations

Country	Name	City	State
Uganda	Walimu	Kampala

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	National Heart, Lung, and Blood Institute (NHLBI), Walimu

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)