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Community Initiated Preventive Therapy for TB (CHIP-TB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04369326
Recruitment Status : Not yet recruiting
First Posted : April 30, 2020
Last Update Posted : April 30, 2020
Sponsor:
Collaborators:
UNITAID
Aurum Institute
KNCV Tuberculosis Foundation
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

Background: The World Health Organization (WHO) currently recommends household contact investigation for new tuberculosis (TB) patients in low- and middle-income countries, with an emphasis on pediatric contacts. Although the aim of this policy is to find previously undetected TB patients and reduce transmission, such investigations represent a missed opportunity to start contacts without TB on preventive therapy (TPT). The WHO guidelines do not address the optimal implementation of contact investigation. The standard of care (SOC) in most settings, passive referral of pediatric contacts to the clinic by the index TB patient, has largely remained unsuccessful in practice. In 2017, the WHO estimated only 23% of eligible child contacts were started on TB preventive therapy. Household contact investigation has been shown to have a higher yield in active TB case finding, but is labor intensive, and may be challenging to implement in densely populated urban settings or informal settlements/slums. The WHO recently endorsed the use of a new TPT regimen (rifapentine and isoniazid weekly (3HP)) for both children and adults in high burden settings, and the programmatic roll out of this regimen offers the opportunity to simultaneously examine new strategies to improve the identification and treatment of pediatric TB household contacts.

Objective: To compare the effectiveness of community-based versus facility-based child contact investigation and delivery of TB preventive care to inform the optimal implementation strategy for investigating pediatric household TB contacts.

Study Design: Cluster-randomized trial in 32 clinics (16 clinics per arm) divided equally among South Africa and Ethiopia (8 clinics per arm per country).

Methods: Newly diagnosed qualifying TB index patients (determined by South African or Ethiopian National TB guidelines) and participants' household child contacts will be recruited to participate. Local staff, including the relevant nurses and community health workers in the intervention and control clinics, will be trained to conduct contact investigation with a symptom-based approach for all child contacts under 15 years old in home and at the clinic. Data will be collected using routine medical files and then retrospectively abstracted by the research team. Thirty-two primary health clinics will be stratified (by TB case notification and by country) and randomized in 1:1 fashion to either community-based or facility-based delivery of care. Household child contacts under 15 years of age who screen negative for TB disease will be initiated on TPT by a healthcare worker (nurse, community health worker, etc.) either in the home or clinic setting. Children in the intervention arm who screen positive will first be sent to the nurse at the clinic for repeat screening. Children who have a persistently positive screen in the intervention arm and those with a positive screen in the control arm using South Africa's or Ethiopia's pediatric symptom screening tool will be referred to a physician at the district hospital for further investigation of TB disease, as is the standard of care in both settings. Investigators will compare clinic-level outcomes including proportion of household TB contacts under 15 years of age that were screened, initiated on TPT, and who completed TPT, and reasons for not completing TPT including loss to follow up and incident TB disease while on TPT.


Condition or disease Intervention/treatment Phase
Tuberculosis Other: Community-Based TPT Initiation Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Cluster-randomized trial
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Community Initiated Preventive Therapy for TB (CHIP-TB Trial)
Estimated Study Start Date : January 1, 2021
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : March 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Experimental: Community-Based TPT Initiation
All TB index patients who agree to participate will have a home visit by clinic staff who will perform: (1) contact enumeration (2) TB symptom screening of all children <15 years (3) Initiation of TPT for all asymptomatic children and (4) Referral of all symptomatic children less than 15 years, including those living with HIV. HIV testing will be offered to all child contacts 12 months of age and older. Those children less than 12 months will be referred to the clinic for HIV testing, if indicated by local guidelines. In South Africa, these home visits will occur by a combination of community health workers and professional nurses. In Ethiopia, home visits will occur by health extension workers supported by nurses.
Other: Community-Based TPT Initiation
Community-based care delivery model for pediatric tuberculosis evaluation and initiation of preventive therapy

No Intervention: Facility-Based TPT Initiation
Children less than 15 years living in the home of TB index patients who agree to participate in the study will be referred to clinic for TB symptom screening and initiation of TPT for all asymptomatic child contacts. Symptomatic child contacts will be referred to a physician for evaluation, as is currently the standard of care. Additionally, child contacts identified in any maternal and child health program will be referred to the TB clinic for TB symptom screening. HIV testing will be offered at the clinic for all child contacts and will be performed according to local guideline.



Primary Outcome Measures :
  1. The cluster-level ratio of the number of household child contacts less than 15 years of age initiated on TB preventive therapy (TPT) per index patient, comparing the intervention to the control arm [ Time Frame: 4 months ]
    TPT includes 3 months of weekly rifapentine and isoniazid, 3 months of daily rifampin and isoniazid or 6 months of isoniazid


Secondary Outcome Measures :
  1. The cluster-level ratio of the number of household child contacts less than 15 years of age identified per index patient, comparing the intervention to the control arm [ Time Frame: 4 months ]
  2. The cluster-level proportions of estimated child contacts under 15 years who are identified [ Time Frame: 6 months ]
    We will calculate the estimated child contacts per household using Demographic and Health Survey data and prior community-based contact tracing studies in both South Africa and Ethiopia. We will measure identified child TB contacts using the index patient's clinic-based contact tracing report, the child contact management file and the community-level file maintained by community health teams.

  3. The cluster-level proportions of estimated child contacts under 15 years who are screened [ Time Frame: 6 months ]
    We will calculate the estimated child contacts per household using Demographic and Health Survey data and prior community-based contact tracing studies in both South Africa and Ethiopia. We will define screening as the child's documented visit to the TB clinic or a documented visit to the home by the community health team (where the child was present) within four months of the index patient's TB clinic admission.

  4. The cluster-level proportions of estimated child contacts under 15 years who are initiated on TB preventive therapy [ Time Frame: 6 months ]
    We will calculate the estimated child contacts per household using Demographic and Health Survey data and prior community-based contact tracing studies in both South Africa and Ethiopia. Clinic staff or community health workers will document TPT initiation on the child contact management file.

  5. The cluster-level proportions of estimated child contacts under 15 years who complete TB preventive therapy [ Time Frame: 6 months ]
    We will calculate the estimated child contacts per household using Demographic and Health Survey data and prior community-based contact tracing studies in both South Africa and Ethiopia. Clinic staff or community health workers will document TPT completion on the child contact management file.

  6. The cluster-level ratio of the number of household child contacts less than 15 years of age initiated on TB preventive therapy per index patient, comparing the intervention to the control arm in South Africa [ Time Frame: 4 months ]
  7. The cluster-level ratio of the number of household child contacts less than 15 years of age initiated on TB preventive therapy per index patient, comparing the intervention to the control arm in Ethiopia [ Time Frame: 4 months ]
  8. The cluster-level ratio of the number of household child contacts less than 15 years of age initiated on TB preventive therapy per index patient, comparing the intervention to the control arm among those less than 5 years of age [ Time Frame: 4 months ]
  9. The proportion of child contacts, by study arm, who discontinued TPT due to incident TB [ Time Frame: 6 months ]
  10. The proportion of child contacts, by study arm, who discontinued TPT due to pregnancy [ Time Frame: 6 months ]
  11. The proportion of child contacts, by study arm, who discontinued TPT due to severe malaria [ Time Frame: 6 months ]
  12. The proportion of child contacts, by study arm, who discontinued TPT due to a side effect [ Time Frame: 6 months ]
  13. The proportion of child contacts, by study arm, who were lost to follow up [ Time Frame: 6 months ]
  14. The proportion of children, by study arm, who were HIV-tested [ Time Frame: 3 months ]
  15. The proportion of newly diagnosed HIV-positive children, by study arm, who are referred for initiation of antiretroviral therapy by the community health team [ Time Frame: 3 months ]
  16. The proportion of newly diagnosed HIV-positive children, by study arm, who are initiated on antiretroviral therapy [ Time Frame: 3 months ]
  17. The proportion of identified child contacts in the intervention arm whose caregiver agrees for them to be screened by community-based healthcare workers in their home [ Time Frame: 4 months ]
  18. Mean number of attempted household visits per household [ Time Frame: 6 months ]
  19. Mean duration of time per household visit [ Time Frame: 6 months ]
  20. The proportion of TB contacts initiated on the correct TPT regimen by age and HIV status [ Time Frame: 6 months ]
  21. The proportion of TPT initiations with the correct dose for weight [ Time Frame: 6 months ]
  22. Proportion of TB index patient households in the intervention arm who refused a household visit due to stigma [ Time Frame: 6 months ]
  23. Proportion of TB index patient households in the intervention arm who refused a household visit due to lack of time [ Time Frame: 6 months ]
  24. Proportion of TB index patient households in the intervention arm who refused a household visit due to well status of the child [ Time Frame: 6 months ]
  25. Proportion of TB index patient households in the intervention arm who do not receive a home visit because the family and/or child was not home on three separate attempts [ Time Frame: 6 months ]
  26. Proportion of TB index patient households in the intervention arm who refused a household visit due to fear of disclosure [ Time Frame: 6 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion Criteria for Index Patient in South Africa:

  • Adult pulmonary TB patient being treated for pulmonary TB disease (with bacteriologic confirmation including smear, GeneXpert® MTB/RIF and/or liquid mycobacterial culture) in one of the participating clinics
  • Willing to have a home visit and disclose their diagnosis to household members
  • Lives in the catchment areas of a study clinic
  • Age 18 years or older
  • Provides informed consent

Inclusion Criteria for Index Patient in Ethiopia:

  • Adult or child being treated for pulmonary TB disease (clinical with or without microbiologic diagnosis) in one of the participating clinics
  • Willing to have a home visit and disclose their diagnosis to household members
  • Lives in the catchment areas of a study clinic
  • Age 18 years or older
  • Provides informed consent

Inclusion Criteria for Contact in South Africa:

  • Child less than 15 years old living in the household of the TB index patient
  • Caregiver willing to provide informed consent
  • Children 7 years and older must also provide assent

Inclusion Criteria for Contact in Ethiopia:

  • Child less than 15 years old living in the household of the TB index patient
  • Caregiver willing to provide informed consent
  • Children 12 years and older must also provide assent

Exclusion Criteria:

Exclusion Criteria for Index Patient in South Africa and Ethiopia:

  • Extrapulmonary TB with no evidence of concurrent pulmonary TB
  • Evidence of rifampin and/or isoniazid resistance on GeneXpert® MTB/RIF or drug sensitivity testing performed on M. tuberculosis isolates identified on culture
  • Household has already participated in study (more than one index patient in the household) and child contacts under 15 years have already been evaluated and remain on TPT and/or TB treatment

Exclusion Criteria for Contact in South Africa:

  • Household child contact of a drug-resistant TB index patient. (Drug resistance defined either by the presence of rifampin resistance on GeneXpert® MTB/RIF OR drug sensitivity testing on isolates identified by culture).

Exclusion Criteria for Contact in Ethiopia:

  • Household child contact of a drug-resistant TB index patient. (Drug resistance defined either by the presence of rifampin resistance on GeneXpert® MTB/RIF OR drug sensitivity testing on isolates identified by culture).
  • Household contact 15 years and older

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04369326


Contacts
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Contact: Nicole Salazar-Austin, MD 443-287-2266 nsalaza1@jhmi.edu
Contact: Jonathan Golub, PhD jgolub@jhmi.edu

Sponsors and Collaborators
Johns Hopkins University
UNITAID
Aurum Institute
KNCV Tuberculosis Foundation
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04369326    
Other Study ID Numbers: IRB00249787
First Posted: April 30, 2020    Key Record Dates
Last Update Posted: April 30, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections