Community-based Tuberculosis Tracing and Preventive Therapy

Study Overview
=================
Brief Summary
-----------------
The many gaps observed in the cascade of care of tuberculosis (TB) child contacts occur mostly in the screening, preventive therapy (PT) initiation and PT completion steps and the main drivers of these gaps are considered to be the health system infrastructure, limited worker resources and parents' reluctance to bring their children to the facility for screening. There would be great advantages of using a symptom-based screening at community level where only the symptomatic contacts are referred to hospital for further evaluation and asymptomatic contacts are started on PT in the community. Household or community-based screening is likely to improve the uptake and acceptability of child contact screening and management as well as adherence to PT and to reduce cost and workload at facility level. This study proposes to compare the cascade of care between two models for TB screening and management of household TB child contacts in two high TB burden and limited resource countries, Cameroon and Uganda. In the facility-based model, children will be screened at facility (Cameroon) or household level (Uganda) and preventive therapy initiation, refills of PT therapy and follow-up will be done at facility level. In the intervention group (community-based model), child contacts will be screened in the household by a community health worker (CHW). Those with symptoms suggestive of TB will be referred to the facility for TB investigations. Asymptomatic child contacts from high risk groups (under-5 years or HIV infected 5-14) will be initiated on PT (3 months isoniazid-rifampicin) in the household. Refills of PT therapy will also be done in the communities by the CHW. In both models, symptomatic children requiring further investigations for TB diagnosis will be referred to a health facility.

Detailed Description
-----------------
The primary study objective is to compare the proportion of household child TB contacts eligible for PT (under-5 years and HIV-infected children 5-14 years without active TB) who initiate and complete PT using facility-based and decentralized community-based models of care for contact screening and management. Secondary objectives are: To compare the facility and community-based models in terms of: The full cascade of care for the initiation and completion of PT in child TB contacts < 5 years or HIV+ children 5-14 years . Cascade of care for the detection and treatment of TB in child contacts (all ages): PT tolerability and adherence among eligible child contacts initiated on PT. Treatment uptake and outcomes for child contacts diagnosed with TB . Child contact outcomes at 6 months after enrollment for all child contacts. Acceptability by the parents/guardians, health personnel and community of the different models of care. Cost and cost-effectiveness of the different models. Fidelity of the implementation of the model activities as compared to the protocol. To assess the number of adult contact cases diagnosed with TB through the community-based screening. To compare between the pre- (baseline assessment) and post-intervention (by model of care) data related to: Children diagnosed with TB and registered at facility level and their treatment outcome. Adults diagnosed with TB and registered at facility level and their treatment outcome. PT initiation and outcomes. This study will be implemented under the frame of the Catalyzing Pediatric TB Innovation (CaP TB) Project, funded by Unitaid and implemented by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF). The goal of CaP TB is to improve the pediatric TB morbidity and mortality by catalyzing the wide uptake of the new first-line fixed dose combination drugs for children and optimizing the use of these drugs through improved case detection and innovative models of care. In both models of care, contacts with TB suggestive symptoms will be investigated for TB at the cluster facility that is supported by EGPAF within the CaP TB project. In Cameroon the CaP TB project will be implemented in the Central and Littoral regions and in Uganda in the South-West region.

Official Title
-----------------
Community Intervention for Tuberculosis Active Contact Tracing and Preventive Therapy - a Cluster Randomized Study (CONTACT)

Conditions
-----------------
Tuberculosis

Intervention / Treatment
-----------------
* Other: Screening and initiating preventive therapy in communities


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion of the index cases Age > 15 years Newly bacteriologically confirmed TB case (less than a month since diagnosis) Reports child contact(s) Written informed consent signed by the index case and by parents/guardians for minors or incapacitated people Inclusion of contacts Household contact Age Facility-based model in Cameroon: < 5 years or HIV infected 5-14 years and all self-referred adults or children*. Facility-based model in Uganda and community-based model on both countries: all ages Written informed consent signed by adult contacts and by parents/guardians for minors or incapacitated people Written assent for children > 7 years in Cameroon and ≥8 years in Uganda Under the facility-based model in Cameroon, although there is no systematic request to screen adults or HIV-negative child contacts 5-14 years old, first inclusions showed that some of them came by themselves for TB screening. This justifies their inclusion in the study in order to ensure the completeness of data for all contacts screened under the facility-based model. Exclusion Criteria: - Exclusion of index cases Index cases who do not have child household contacts living in the catchment area of one of the study clusters Index cases diagnosed with rifampicin resistance, multidrug-resistant (MDR) or extensively drug-resistant (XDR) TB *Index cases from a household screened within the CONTACT study and that does not declare child contacts from another household.* Index cases that are prisoners TB confirmed adult contacts cases living in the same household as an index case already enrolled in the study will not be included as new index cases unless they declare additional contacts from another household - Exclusion of the contacts If the contact is already on PT or on TB treatment
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Clusters were selected among facilities participating in the first phase of the CAP-TB project following an initial facility assessment for participating in the CAP-TB project. Facilities with diagnostic and treatment capacity and detecting and minimum of 50 bacteriologically confirmed pulmonary TB cases per year in a rural/semi-rural or semi-urban setting were selected. The facilities correspond to district hospitals in Cameroon and health center IV or district hospitals in Uganda. Twenty clusters will be randomized between the intervention and the facility-based model. The randomization unit (cluster) will be the facility where TB cases (index cases) are diagnosed and its catchment area.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Facility-based model<br>Standard of care of each country | |
| Experimental: Community-based model<br>Screening and initiating preventive therapy in communities | Other: Screening and initiating preventive therapy in communities<br>* Symptom-based screening of tuberculosis household child contacts by community health workers; initiation of preventive therapy (3 months of a fixed-dose combination of rifampicin-isoniazid or 6 months isoniazid for HIV+ children on protease inhibitors) in the household by a nurse; follow-up of children under preventive therapy by a community health worker for eligible children at community level, and referral of presumptive tuberculosis cases (children and adults) to the facility.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion of preventive therapy | Proportion of child TB contacts <5 years of age and HIV-infected children of 5-14 years of age who initiate and complete the PT of all child contacts <5 years of age and HIV-infected children of 5-14 years of age declared by the index case | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of children screened | Number of children screened among child contacts <5 years or HIV-infected 5-14 years declared by the index case | 6 months | 
| Proportion of children eligible for PT | Number of children eligible for PT among screened children | 6 months | 
| Proportion of children started on PT | Number of children started on PT among those eligible for PT | 6 months | 
| Proportion of children who did not complete PT | Number of children who did not complete PT among those started on PT | 6 months | 
| Proportion of children with presumptive TB | Number of children with symptoms suggestive of TB among screened children (< 15 years) | 1 month | 
| Proportion of children investigated for TB | Number of children with presumptive TB investigated for TB | 1 month | 
| Proportion of children diagnosed with TB | Number of children diagnosed with TB among those with symptoms suggestive of TB | 1 month | 
| Proportion of children started on TB treatment | Number of children with TB diagnosis who are started on TB treatment | 1 month | 
| Proportion of adult contacts screened | Number of adult contacts screened among household identified adult contacts | 1 month | 
| Proportion of adults presumptive TB cases | Number of adults with symptoms suggestive of TB among those screened for TB | 1 month | 
| Proportion of adults diagnosed with TB | Number of adults presumptive TB cases diagnosed with TB | 1 month | 
| Proportion of children with serious adverse events | Number of children with serious adverse events among children started on PT | 6 months | 
| Proportion of children with adverse event of interest | Number of children with adverse event of interest (peripheral neuropathy, clinical hepatotoxicity) among children on PT | 6 months | 
| Treatment adherence | Ratio of PT dose taken by the child over the total number of doses prescribed | 6 months | 
| Treatment outcomes of children started on TB treatment | Cured Treatment completed Failure Death Lost to follow up Transferred out | 6 months | 
| Proportion of children diagnosed with TB | Number of children diagnosed with TB after initiation of PT or children not initiated on PT and not diagnosed with TB at baseline | 6 months | 
| TB case detection during pre-intervention period | Number of patients registered in the facility TB register one year before intervention | 2 years | 
| Proportion of children among all registered TB cases during pre-intervention period | Number of children among all patients diagnosed with TB and registered in the facility TB register one year before intervention | 2 years | 
| TB treatment outcome of registered TB patients during pre-intervention period | Cured Treatment completed Failure Death Lost to follow up Transferred out | 2 years | 
| Number of children started on PT during pre-intervention period | Number of children started on PT from the facility PT register one year before intervention | 2 years | 
| Completion rate of children started on PT intervention during pre-intervention period | Number of children who completed PT among those started on PT from the facility PT register one year before | 2 years | 
| Number of household visits by CHW | Number of visits by the CHW to the household for contact screening per household | 2 years | 
| Proportion of parents/guardians who accept household visit | Acceptability of household visit for contact screening | 2 years | 
| Reasons of refusal of household visit | Description of screening failures | 2 years | 
| Preference for household visit versus facility visit | This outcome measures whether the parent/guardian prefers bringing child to the facility rather than having someone coming to his household | 2 years | 
| Critical events experienced by CHW during household visit | Description of critical events during house visit and how these where dealt with | 2 years | 
| Transport cost for household visit by CHW | Cost of transportation for the CHW to go from the health facility to a household | 2 years | 
| Transport cost for parents/guardian for facility-based screening | Cost supported by families to bring child contact to the facility for screening | 2 years | 
| Time spent to perform household contact screening visit | It includes the time to reach the household, the time spent in the household and the time to go back to the facility for CHW | 2 years | 
| Proportion of delivered activities compared to the intended activities of the model | This outcome will assess fidelity to study procedures | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Children, Contact tracing, Preventive therapy, Prophylaxis, Community health workers, Community-based distribution, Standard of care, Screening, Randomized controlled trial, Cameroon, Uganda, Patient outcome assessment