Kharituwe TB Contact Tracing Study

Sponsor
Johns Hopkins Bloomberg School of Public Health (Other)
Overall Status
Recruiting
CT.gov ID
NCT04520113
Collaborator
Perinatal HIV Research Unit of the University of the Witswatersrand (Other), Setshaba Research Centre (Other)
15,000
2
3
45
7500
166.8

Study Details

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
  • Behavioral: Household contact tracing
N/A

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
Anticipated 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 :
Sep 1, 2020
Anticipated Primary Completion Date :
Jan 1, 2024
Anticipated Study Completion Date :
Jun 1, 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 [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 [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. [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 [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 [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 [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 [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 [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

Criteria

Ages Eligible for Study:
0 Years to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Locations

Site City State Country Postal Code
1 Perinatal HIV Research Unit (PHRU) Johannesburg South Africa
2 Setshaba Research Centre Soshanguve South Africa

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Johns Hopkins Bloomberg School of Public Health
ClinicalTrials.gov Identifier:
NCT04520113
Other Study ID Numbers:
  • R01AI147681
First Posted:
Aug 20, 2020
Last Update Posted:
Feb 15, 2021
Last Verified:
Feb 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
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:

Study Results

No Results Posted as of Feb 15, 2021