TuberculosisKharitode TBNCT02808507

Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa

A study testing Active TB case finding in people with Tuberculosis, run by Johns Hopkins Bloomberg School of Public Health at 2 sites in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 0 to 99 yearsHealthy volunteers can take part
Conditions the study is for: Tuberculosis
What is being tested?: Active TB case finding
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4,852 participants
Where: 2 sitesSouth Africa
Study dates: 18 Jul 2016to 30 Jan 2020
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 0 to 99 years
All sexes
Healthy volunteers accepted
Child, Adult, Older adult

Who may be able to join

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

Show all 16Show fewer

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)

Who cannot join

Unable to provide informed consent.

Trial locations and contacts

2 sites in 1 country.

South Africa2 sites

Vhembe health subdistrict
Louis Trichardt, Limpopo
Waterberg health subdistrict
Mokopane, Limpopo

Other trials in South Africa

About this study

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.

Conditions: Tuberculosis
Being tested: Active TB case finding
Medical subject headings: Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Active TB case findingOther
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.

Study groups in NCT02808507
Study group	Role	What they receive
Facility-based screening	Experimental	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. Receives: Other: Active TB case finding
Contact screening	Experimental	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. Receives: Other: Active TB case finding

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 18 months
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.
Measured: 36 months

Secondary outcomes (5)

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.
Measured: 36 months
Total Cost of Household Contact Investigation Strategies
This measure is the total cost of household contact investigation in both the household-based and incentive-based arms in 2018 United States dollar (USD) collected from the societal perspective (including both health systems and patient-level costs). As these are actual measured (not estimated) costs, no 95% confidence interval is reported.
Measured: 36 months
Estimated Costs Per Contact Person Screened in the Household-based and Incentive-based Contact Investigation Arms
These are estimated costs in 2018 USD for the cost per contact person screened in each arm, collected from the societal perspective including health system and patient-level costs.
Measured: 36 months
Cost Per Secondary Case of TB Identified Among Contacts, Per Arm
Cost were measured in 2018 US dollars from the societal perspective, including both health systems and patient level costs. Total costs per arm were divided by the number of secondary TB cases identified among contacts in that arm.
Measured: 36 months
Incremental Cost-effectiveness Ratio
(Total costs of incentive-based contact investigation-total costs of household-based contact investigation)/(effectiveness of incentive-based contact investigation-effectiveness of household-based contact investigation)
Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Jul 201630 Jan 2020

First posted21 Jun 2016 (estimated)
Study start18 Jul 2016
Primary completion17 Jan 2018
Study completion30 Jan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for TuberculosisStudies of the same condition, open and under way.
More trials run by Johns Hopkins Bloomberg School of Public HealthThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 4,852 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02808507
Sponsor's protocol ID: 15-0005
Other IDs: R01AI116787-02
Acronym: Kharitode TB
Status last verified: Aug 2024
First submitted: 1 Jun 2016
Last updated: 5 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 34212181
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.
PubMed 31039165
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.
PubMed 28558737

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa
ClinicalTrials.gov ID: NCT02808507
Acronym / sponsor ID: Kharitode TB / 15-0005
Conditions: Tuberculosis
Study type: Interventional
Recruitment status: Completed
Enrolment: 4,852 participants (actual)
Lead sponsor: Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID), Perinatal HIV Research Unit of the University of the Witswatersrand
Study start: 18 Jul 2016 (actual)
Primary completion: 17 Jan 2018 (actual)
Study completion: 30 Jan 2020 (actual)
First posted: 21 Jun 2016 (estimated)
Results: Posted 2 Dec 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Facility-based screening	Experimental	Other: Active TB case findingThis 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.
Contact screening	Experimental	Other: Active TB case findingThis 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.

Who may qualify

Ages: 0 to 99 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (16 listed)

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

Key exclusion criteria (1 listed)

Unable to provide informed consent.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Active TB case findingActive 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.	Other	Contact screening, Facility-based screening

Primary outcome

Treatment Initiation Ratio in Facility Versus Contact Investigation Clinics
Time frame: 18 months
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
Time frame: 36 months
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.

5 secondary outcomes

Comparative Number of Secondary TB Cases Identified in Incentive-based Versus Household-based Contact Tracing
Time frame: 36 months
Total Cost of Household Contact Investigation Strategies
Time frame: 36 months
Estimated Costs Per Contact Person Screened in the Household-based and Incentive-based Contact Investigation Arms
Time frame: 36 months
Cost Per Secondary Case of TB Identified Among Contacts, Per Arm
Time frame: 36 months
Incremental Cost-effectiveness Ratio
Time frame: 36 months

Results and safety

Results posted to the registry on 2 Dec 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Facility-based Screening Arm	1,929	1,929
Contact Tracing Household-based Sub-arm	1,413	1,413
Contact Tracing Incentive-based Sub-arm	1,510	1,510

Primary outcome: Treatment Initiation Ratio in Facility Versus Contact Investigation Clinics

Time frame: 18 months. Count of participants. Unit: Participants

Measure	Facility-based Screening n = 1929	Contact Screening n = 1726
Value	1929	1726

Facility-based Screening vs Contact Screening: Treatment initiation ratio: 1.04 (95% CI 0.80 to 1.3), p = 0.73, See above comments

Population analysed: The population for this outcome consists of a sub-group of the total study population (those enrolled during the intervention period of July 18,2015 - January 17, 2018). All participants from the facility-based screening arm are included (n=1929), and the participants of the contact screening arm (n=1726) are included (this is a combination from the household-based and incentive-based screening arms).

Primary outcome: Comparative Treatment Initiation Ratio in the Incentive-based Versus Household-based Contact Investigation Arms

Time frame: 36 months. Count of participants. Unit: Participants

Measure	Contact Tracing Household-based Sub-arm n = 1413	Contact Tracing Incentive-based Sub-arm n = 1510
Value	1413	1510

Contact Tracing Household-based Sub-arm vs Contact Tracing Incentive-based Sub-arm: Treatment initiation ratio: 1.05 (95% CI 0.97 to 1.13), p = 0.68, Poisson regression

Population analysed: This analysis population includes all participants enrolled in the two contact tracing sub-arms during the total study period of 36 months. It excludes participants from the facility-based screening arm. A total of 2,923 patients were started on TB treatment during the study period: 1,413 in clinics allocated to household-based contact investigation and 1,510 in clinics allocated to incentive-based contact investigation.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 36 months of study data collection, lasting from July 2016-January 2020.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Facility-based Screening Arm	0 of 1,929 (0%)	0 of 1,929 (0%)	0 of 1,929
Contact Tracing Household-based Sub-arm	0 of 1,413 (0%)	0 of 1,413 (0%)	0 of 1,413
Contact Tracing Incentive-based Sub-arm	0 of 1,510 (0%)	0 of 1,510 (0%)	0 of 1,510

Limitations and caveats (from the sponsor): * Clinics were purposively chosen based on having larger historical TB patient volume; findings may not generalize to smaller, more remote clinics. * Clinics and patients not blinded to allocation, so cannot rule out possibility of resultant bias. * 1/3 of the index patients with TB whom we approached for enrollment refused or were unable to be enrolled, and cannot rule out that they may have differed in some way associated with TB incidence among their contacts from those able to be enrolled.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34212181Baik 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.
Derived from this study: PubMed 31039165Hanrahan 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.
Derived from this study: PubMed 28558737Kerrigan 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.

Related trials for Tuberculosis

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Dowdy, MD, PhD principal investigator

Johns Hopkins Bloomberg School of Public Health

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Active TB case finding in people with Tuberculosis, run by Johns Hopkins Bloomberg School of Public Health at 2 sites in South Africa.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Initiation Ratio in Facility Versus Contact Investigation Clinics (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02808507, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2024.