Clinical trial NCT04369326: Community Initiated Preventive Therapy for TB
Official title: Community Initiated Preventive Therapy for TB (CHIP-TB Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: UNITAID
name: Aurum Institute
name: KNCV Tuberculosis Foundation
First posted: 2020-04-30
Enrollment: 1168
Sex: ALL
Minimum age (years): 0
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cluster-randomized trial
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 4 months
Secondary outcomes:
measure: 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
timeFrame: 4 months
measure: The cluster-level proportions of estimated child contacts under 15 years who are identified
timeFrame: 6 months
measure: The cluster-level proportions of estimated child contacts under 15 years who are screened
timeFrame: 6 months
measure: The cluster-level proportions of estimated child contacts under 15 years who are initiated on TB preventive therapy
timeFrame: 6 months
measure: The cluster-level proportions of estimated child contacts under 15 years who complete TB preventive therapy
timeFrame: 6 months
measure: 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
timeFrame: 4 months
measure: 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
timeFrame: 4 months
measure: 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
timeFrame: 4 months
measure: The proportion of child contacts, by study arm, who discontinued TPT due to incident TB
timeFrame: 6 months
measure: The proportion of child contacts, by study arm, who discontinued TPT due to pregnancy
timeFrame: 6 months
measure: The proportion of child contacts, by study arm, who discontinued TPT due to severe malaria
timeFrame: 6 months
measure: The proportion of child contacts, by study arm, who discontinued TPT due to a side effect
timeFrame: 6 months
measure: The proportion of child contacts, by study arm, who were lost to follow up
timeFrame: 6 months
measure: The proportion of children, by study arm, who were HIV-tested
timeFrame: 3 months
measure: The proportion of newly diagnosed HIV-positive children, by study arm, who are referred for initiation of antiretroviral therapy by the community health team
timeFrame: 3 months
measure: The proportion of newly diagnosed HIV-positive children, by study arm, who are initiated on antiretroviral therapy
timeFrame: 3 months
measure: 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
timeFrame: 4 months
measure: Mean number of attempted household visits per household
timeFrame: 6 months
measure: Mean duration of time per household visit
timeFrame: 6 months
measure: The proportion of TB contacts initiated on the correct TPT regimen by age and HIV status
timeFrame: 6 months
measure: The proportion of TPT initiations with the correct dose for weight
timeFrame: 6 months
measure: Proportion of TB index patient households in the intervention arm who refused a household visit due to stigma
timeFrame: 6 months
measure: Proportion of TB index patient households in the intervention arm who refused a household visit due to lack of time
timeFrame: 6 months
measure: Proportion of TB index patient households in the intervention arm who refused a household visit due to well status of the child
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: Proportion of TB index patient households in the intervention arm who refused a household visit due to fear of disclosure
timeFrame: 6 months
Other outcomes:
Locations:
city: Oromia Region
country: Ethiopia
facility: KNCV-Ethiopia
state: Oromia
Study officials:
affiliation: Johns Hopkins University
name: Nicole Salazar-Austin, MD
role: PRINCIPAL_INVESTIGATOR
References: