Kharituwe TB Contact Tracing Study

• ClinicalTrials.gov Identifier: NCT04520113
• Recruitment Status: Recruiting
• First Posted: August 20, 2020
• Last Update Posted: February 15, 2021
• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: Perinatal HIV Research Unit of the University of the Witswatersrand; Setshaba Research Centre
• Information provided by (Responsible Party): Johns Hopkins Bloomberg School of Public Health

Study Description

Brief Summary:

The purpose of this study is to characterize the role of human mobility in fueling TB epidemics and estimate the potential impact of innovative case finding interventions tailored to mobile populations

Condition or disease	Intervention/treatment	Phase
Tuberculosis; Hiv	Behavioral: Household contact tracing	Not Applicable

Detailed Description:

The investigators propose a randomized trial of two novel TB case-finding interventions among household members of patients diagnosed with active TB: holiday-based screening in a rural South African province (Limpopo) and off-peak (weekend/evening) screening in an urban settlement into which many residents of Limpopo migrate for work. The investigators will enroll index cases of TB plus their household contacts in each setting and randomize them to novel versus standard contact investigation. In Specific Aim 1, investigators will use whole genome sequencing of all cases, overlaying transmission trees with data on human movement, to evaluate associations between mobility and TB transmission in this population. In Specific Aim 2, investigators will employ a multidisciplinary approach to compare novel versus standard contact investigation in each setting along the following dimensions: (a) effectiveness (number of secondary TB cases diagnosed and starting treatment); (b) implementation (reach, fidelity, and maintenance of contact investigation outside of business hours); (c) cost-effectiveness (cost per disability-adjusted life year) and budget impact; and (d) projected population-level impact on TB incidence. Successful completion of these aims will have long-term impact by characterizing the role of mobility in fueling TB epidemics and testing two tailored approaches to improve TB control in highly mobile populations - an underserved group that is increasingly recognized as playing a major role in global TB transmission.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Masking Description: The principal investigators are blinded as to the assignment of treatment to participants
• Primary Purpose: Diagnostic
• Official Title: Innovative Contact Tracing Strategies for Detecting TB in Mobile Rural and Urban South African Populations
• Actual Study Start Date: September 1, 2020
• Estimated Primary Completion Date: January 2024
• Estimated Study Completion Date: June 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard Tracing; Households of tuberculosis index patients receive "standard" household contact tracing during regular weekday business hours.	Behavioral: Household contact tracing; Household contact tracing to test and diagnose Tuberculosis of household contacts of Tuberculosis patients.
Experimental: Holiday Tracing; Households of tuberculosis index patients in rural South Africa receive household contact tracing during holidays (Christmas and Easter).	Behavioral: Household contact tracing; Household contact tracing to test and diagnose Tuberculosis of household contacts of Tuberculosis patients.
Experimental: Evening / Weekend Tracing; Households of tuberculosis index patients in urban South Africa receive household contact tracing during evenings and weekends.	Behavioral: Household contact tracing; Household contact tracing to test and diagnose Tuberculosis of household contacts of Tuberculosis patients.

Outcome Measures

Primary Outcome Measures :

1. Effectiveness: ratio of secondary TB identified and started on treatment per index case in novel strategy arm compared to standard contact investigation arm [ Time Frame: Duration of study (30 months) ]
   The ratio of the number of secondary TB cases identified and started on treatment per index case in the novel strategy arm (off-peak screening in Soshanguve and holiday screening in Limpopo) compared to index cases receiving standard contact investigation.

Secondary Outcome Measures :

1. The TB prevalence ratio, comparing highly mobile to less mobile index patients [ Time Frame: Duration of study (30 months) ]
   The TB prevalence ratio, comparing highly mobile to less mobile individuals, measuring mobility on two scales (neighborhood/intra-urban and regional/intra-national). For the analysis: amount of time spent in transit, truncating long excursions at 50km (one hour).
2. TB strain relatedness using maximum likelihood transmission trees. [ Time Frame: Duration of study (30 months) ]
   TB natural history, epidemiological, and whole genome sequencing (WGS)-derived phylogenetic data will be integrated into a statistical modeling framework to draw probabilistic conclusions about the likelihood of transmission between persons. "Transmitters" will be defined as individuals from whom at least one secondary case most likely originated.
3. Relative acceptability of each novel strategy compared to standard contact investigation [ Time Frame: Duration of study (30 months) ]
   Relative acceptability of each novel strategy, compared against routine contact investigation. Acceptability of the intervention will be measured among index cases and contacts using a short questionnaire given to a randomly selected participant at a randomly selected 15% of the households visited. The interview will cover acceptability of the visit timing, notification, visit activities (TB screening, HIV testing) and study team interaction among others.
4. Feasibility of each strategy: proportion of potentially eligible index cases for whom a household visit was conducted [ Time Frame: Duration of study (30 months( ]
   Feasibility of each strategy as the proportion of potentially eligible index cases for whom a household visit was conducted. All reasons why visits were unable to be conducted will be recorded (e.g. could not find household, no one ever home, visit not conducted during expected off-peak period).
5. Relative fidelity of each novel strategy compared to standard contact investigation [ Time Frame: Duration of study (30 months) ]
   Relative fidelity of each novel strategy using a process checklist for each index case and household, including whether the household visit was offered and accepted, whether the visit was attempted, whether the visit was successful (i.e., enrolled at least one contact), whether symptom screening and sputum collection were completed and whether newly identified TB cases were notified and referred for treatment.
6. Sustainability of each novel strategy relative to standard contact tracing [ Time Frame: Duration of study (30 months) ]
   Sustainability of each novel strategy by reporting the primary outcome and fidelity measures according to six-month time period over the course of the study.
7. Incremental cost-effectiveness ratio for each novel strategy relative to standard contact tracing [ Time Frame: Duration of study (30 months) ]
   Defined as (cost of contact tracing strategy 2 - cost of strategy 1)/(effectiveness of strategy 2 - effectiveness of strategy 1), where effectiveness is modeled as the number of disability-adjusted life years (DALYs) averted by the intervention. The primary cost-effectiveness measures will be the incremental cost per DALY averted using novel strategies (holiday and off-hours contact tracing) compared to routine contact tracing in each setting separately.

Eligibility Criteria

• Ages Eligible for Study: up to 99 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

TB index cases:

Inclusion criteria:

• Age 0-99 years
• Diagnosed with microbiologically confirmed pulmonary TB at a study hospital or clinic

Exclusion criteria:

• Unwilling/unable to provide informed consent
• Plan not to pursue TB treatment within the study district
• Unwilling/unable to comply with study procedures

Contacts:

Inclusion criteria:

• Age 0-99 years
• Currently resides with or visiting eligible TB index case

Exclusion Criteria:

• Unwilling/unable to provide informed consent
• Unwilling/unable to comply with study procedures

Contacts and Locations

Contacts

Contact: Colleen F. Hanrahan, PhD; 410-502-9289; chanrah1@jhmi.edu

Locations

South Africa

Perinatal HIV Research Unit (PHRU); Recruiting

Johannesburg, South Africa

Contact: Neil Martinson Martinson@phru.co.za

Setshaba Research Centre; Recruiting

Soshanguve, South Africa

Contact: Khatija Ahmed kahmed@setshaba.org.za

Sponsors and Collaborators

Johns Hopkins Bloomberg School of Public Health

Perinatal HIV Research Unit of the University of the Witswatersrand

Setshaba Research Centre

Investigators

• Principal Investigator: David W. Dowdy, MD, PhD; Johns Hopkins Bloomberg School of Public Health

More Information

• Responsible Party: Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT04520113
• Other Study ID Numbers: R01AI147681 ( U.S. NIH Grant/Contract )
• First Posted: August 20, 2020
• Last Update Posted: February 15, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections