Back to resultsComparative Effectiveness/Implementation of TB Case Finding in Rural South Africa (Kharitode TB)
Primary Purpose
Tuberculosis
Status
Completed
Phase
Not Applicable
Locations
South Africa
Study Type
Interventional
Intervention
Active TB case finding
Sponsored by
About this trial
This is an interventional diagnostic trial for Tuberculosis
Eligibility Criteria
Inclusion Criteria:
Facility-based screening arm
- Age 0-99 years
- Informed consent provided (or assent plus parent/guardian consent)
- Attending any of the study 28 study clinics in the facility-based screening arm
Contact tracing arm- Index Case
- Age 0-99 years
- Informed consent provided (or assent plus parent/guardian consent)
- Newly diagnosed (last 2 months) with TB at any of the 28 study clinics in the contact tracing arm
Contact tracing arm- Household Contact
- Age 0-99 years
- Informed consent provided (or assent plus parent/guardian consent)
- Living in the same household as an enrolled Index case (see above)
Contact tracing arm- Non-household Close Contact
- Age 0-99 years
- Informed consent provided (or assent plus parent/guardian consent)
- Referred to the study as a close contact of an enrolled Index case (see above)
Exclusion Criteria (all arms):
- Unable to provide informed consent.
Sites / Locations
- Vhembe health subdistrict
- Waterberg health subdistrict
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Facility-based screening
Contact screening
Arm Description
This strategy will be implemented at all clinics (n=28) within this arm for 18 months. Study staff will encourage providers at each of the clinics to screen all consenting patients attending the clinic, regardless of the original reason for clinic presentation. Upon presenting for care (e.g., while waiting for their healthcare provider), patients will be informed about the study and screened for cough of any duration, fever, weight loss, or night sweats. Participants who are symptomatic and provide a sputum specimen (according to the clinic standard of care) will be given a study flyer informing them that they may be contacted by study staff, and a brief summary of the study. Per standard of care, all sputum samples will be sent to the local National Health Laboratory Service laboratory for Xpert testing.
This arm is comprised of two sub-arms: In the household contact screening sub-arm, a mobile field team visits the household of each consenting newly diagnosed pulmonary TB index case. Each visit consists of a household census, consent of all eligible household members for TB screening, administration of a brief questionnaire, sputum collection for testing with Xpert Mycobacterium tuberculosis (MTB)/rifampin (RIF) and the offer of HIV testing. In the incentive-based contact screening sub-arm, all consenting newly diagnosed active TB cases are provided with 10 coupons for free TB screening to give to close contacts. When a contact presents at clinic with a coupon, they and the index case each receive a small amount of money. If the contact is diagnosed with active TB and starts treatment, the index case receives an additional larger amount of money. Each contact receives a brief questionnaire, TB symptom screen, optional HIV testing, and sputum sample collection for Xpert MTB/RIF.
Outcomes
Primary Outcome Measures
Treatment Initiation Ratio in Facility Versus Contact Investigation Clinics
The primary analysis was based on the facility- level rate ratio, and we first calculated an unadjusted ratio of the treatment initiation rates between the two arms and the corresponding 95% confidence interval (CI). We then adjusted for any residual confounding by district stratification and the historical annual number of people started on TB following a two-stage approach. The first step of this approach fits a Poisson regression to the facility-level counts and the district and historical volume covariates irrespective of study arm. The residuals ratios, calculated as the ratio of the observed over the expected counts, are then used in the second stage to estimate the between-arm rate ratio and the corresponding 95% CI.
Comparative Treatment Initiation Ratio in the Incentive-based Versus Household-based Contact Investigation Arms
The primary outcome of the study was the comparative number of people with incident TB diagnosed and started on treatment at study clinics in the two contact tracing arms, excluding the six-month washout period.
Secondary Outcome Measures
Comparative Costs and Cost-effectiveness of Active TB Case Finding Strategies
The primary outcome for this analysis will be the incremental cost-effectiveness ratio, defined as (cost of ACF strategy 2 - cost of ACF strategy 1 [or no ACF])/(effectiveness of ACF strategy 2 - effectiveness of ACF strategy 1 [or no ACF]), where effectiveness is modeled as the number of disability-adjusted life years (DALYs) averted by the intervention.
Comparative Number of Secondary TB Cases Identified in Incentive-based Versus Household-based Contact Tracing
The pre-specified secondary study outcome was the number of Xpert-based TB diagnoses made among enrolled contacts ("secondary cases") by arm.
Full Information
NCT ID
NCT02808507
First Posted
June 1, 2016
Last Updated
May 25, 2023
Sponsor
Johns Hopkins Bloomberg School of Public Health
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Perinatal HIV Research Unit of the University of the Witswatersrand
1. Study Identification
Unique Protocol Identification Number
NCT02808507
Brief Title
Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa
Acronym
Kharitode TB
Official Title
Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
July 18, 2016 (Actual)
Primary Completion Date
January 17, 2018 (Actual)
Study Completion Date
January 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins Bloomberg School of Public Health
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Perinatal HIV Research Unit of the University of the Witswatersrand
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to compare three strategies for finding TB cases in a rural Sub-Saharan African setting: 1) Screening all attendees of primary care clinics for TB; 2) Conducting household contact investigations of newly diagnosed TB cases; 3) Providing incentives to newly diagnosed TB cases and their contacts to promote contact screening for TB. For each intervention, investigators will measure comparative effectiveness in terms of cases identified as well as the cost-effectiveness and feasibility of implementation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4852 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Facility-based screening
Arm Type
Experimental
Arm Description
This strategy will be implemented at all clinics (n=28) within this arm for 18 months. Study staff will encourage providers at each of the clinics to screen all consenting patients attending the clinic, regardless of the original reason for clinic presentation. Upon presenting for care (e.g., while waiting for their healthcare provider), patients will be informed about the study and screened for cough of any duration, fever, weight loss, or night sweats. Participants who are symptomatic and provide a sputum specimen (according to the clinic standard of care) will be given a study flyer informing them that they may be contacted by study staff, and a brief summary of the study. Per standard of care, all sputum samples will be sent to the local National Health Laboratory Service laboratory for Xpert testing.
Arm Title
Contact screening
Arm Type
Experimental
Arm Description
This arm is comprised of two sub-arms:
In the household contact screening sub-arm, a mobile field team visits the household of each consenting newly diagnosed pulmonary TB index case. Each visit consists of a household census, consent of all eligible household members for TB screening, administration of a brief questionnaire, sputum collection for testing with Xpert Mycobacterium tuberculosis (MTB)/rifampin (RIF) and the offer of HIV testing.
In the incentive-based contact screening sub-arm, all consenting newly diagnosed active TB cases are provided with 10 coupons for free TB screening to give to close contacts. When a contact presents at clinic with a coupon, they and the index case each receive a small amount of money. If the contact is diagnosed with active TB and starts treatment, the index case receives an additional larger amount of money. Each contact receives a brief questionnaire, TB symptom screen, optional HIV testing, and sputum sample collection for Xpert MTB/RIF.
Intervention Type
Other
Intervention Name(s)
Active TB case finding
Intervention Description
Active TB case finding (ACF) refers to any number of strategies used to identify individuals with active TB disease, outside of passive case finding. In passive case finding, individuals with symptoms present at health centers for diagnosis. In active case finding, the health system makes an effort to identify TB cases before they present passively.
Primary Outcome Measure Information:
Title
Treatment Initiation Ratio in Facility Versus Contact Investigation Clinics
Description
The primary analysis was based on the facility- level rate ratio, and we first calculated an unadjusted ratio of the treatment initiation rates between the two arms and the corresponding 95% confidence interval (CI). We then adjusted for any residual confounding by district stratification and the historical annual number of people started on TB following a two-stage approach. The first step of this approach fits a Poisson regression to the facility-level counts and the district and historical volume covariates irrespective of study arm. The residuals ratios, calculated as the ratio of the observed over the expected counts, are then used in the second stage to estimate the between-arm rate ratio and the corresponding 95% CI.
Time Frame
18 months
Title
Comparative Treatment Initiation Ratio in the Incentive-based Versus Household-based Contact Investigation Arms
Description
The primary outcome of the study was the comparative number of people with incident TB diagnosed and started on treatment at study clinics in the two contact tracing arms, excluding the six-month washout period.
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Comparative Costs and Cost-effectiveness of Active TB Case Finding Strategies
Description
The primary outcome for this analysis will be the incremental cost-effectiveness ratio, defined as (cost of ACF strategy 2 - cost of ACF strategy 1 [or no ACF])/(effectiveness of ACF strategy 2 - effectiveness of ACF strategy 1 [or no ACF]), where effectiveness is modeled as the number of disability-adjusted life years (DALYs) averted by the intervention.
Time Frame
3.5 years
Title
Comparative Number of Secondary TB Cases Identified in Incentive-based Versus Household-based Contact Tracing
Description
The pre-specified secondary study outcome was the number of Xpert-based TB diagnoses made among enrolled contacts ("secondary cases") by arm.
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Facility-based screening arm
Age 0-99 years
Informed consent provided (or assent plus parent/guardian consent)
Attending any of the study 28 study clinics in the facility-based screening arm
Contact tracing arm- Index Case
Age 0-99 years
Informed consent provided (or assent plus parent/guardian consent)
Newly diagnosed (last 2 months) with TB at any of the 28 study clinics in the contact tracing arm
Contact tracing arm- Household Contact
Age 0-99 years
Informed consent provided (or assent plus parent/guardian consent)
Living in the same household as an enrolled Index case (see above)
Contact tracing arm- Non-household Close Contact
Age 0-99 years
Informed consent provided (or assent plus parent/guardian consent)
Referred to the study as a close contact of an enrolled Index case (see above)
Exclusion Criteria (all arms):
Unable to provide informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Dowdy, MD, PhD
Organizational Affiliation
Johns Hopkins Bloomberg School of Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vhembe health subdistrict
City
Louis Trichardt
State/Province
Limpopo
Country
South Africa
Facility Name
Waterberg health subdistrict
City
Mokopane
State/Province
Limpopo
Country
South Africa
12. IPD Sharing Statement
Citations:
PubMed Identifier
34212181
Citation
Baik Y, Hanrahan CF, Mmolawa L, Nonyane BAS, Albaugh NW, Lebina L, Siwelana T, Martinson N, Dowdy DW. Conditional Cash Transfers to Incentivize Tuberculosis Screening: Description of a Novel Strategy for Contact Investigation in Rural South Africa. Clin Infect Dis. 2022 Mar 23;74(6):957-964. doi: 10.1093/cid/ciab601.
Results Reference
derived
PubMed Identifier
31039165
Citation
Hanrahan CF, Nonyane BAS, Mmolawa L, West NS, Siwelana T, Lebina L, Martinson N, Dowdy DW. Contact tracing versus facility-based screening for active TB case finding in rural South Africa: A pragmatic cluster-randomized trial (Kharitode TB). PLoS Med. 2019 Apr 30;16(4):e1002796. doi: 10.1371/journal.pmed.1002796. eCollection 2019 Apr.
Results Reference
derived
PubMed Identifier
28558737
Citation
Kerrigan D, West N, Tudor C, Hanrahan CF, Lebina L, Msandiwa R, Mmolawa L, Martinson N, Dowdy D. Improving active case finding for tuberculosis in South Africa: informing innovative implementation approaches in the context of the Kharitode trial through formative research. Health Res Policy Syst. 2017 May 30;15(1):42. doi: 10.1186/s12961-017-0206-8.
Results Reference
derived
Learn more about this trial
Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa
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