Community-based Tuberculosis Tracing and Preventive Therapy

Tuberculosis Clinical Trial

— CONTACT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03832023
• Other study ID #: EG0211
• Status: Completed
• Phase: N/A
• Start date: October 14, 2019
• Est. completion date: August 1, 2022

Study information

• Verified date: February 2023
• Source: Elizabeth Glaser Pediatric AIDS Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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:

1. 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.

2. To assess the number of adult contact cases diagnosed with TB through the community-based screening.

3. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1400
• Est. completion date: August 1, 2022
• Est. primary completion date: August 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Other:
• Screening and initiating preventive therapy in communities
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.

Locations

Country	Name	City	State
Cameroon	Hôpital de district Bonassama	Bonabéri
Cameroon	Hôpital de district Log-Baba	Douala
Cameroon	Centre Médical d'arrondissement Delangue	Edéa
Cameroon	Hôpital de district Mbalmayo	Mbalmayo
Cameroon	Hôpital de district Mfou	Mfou
Cameroon	Hôpital régional Nkongsamba	Nkongsamba
Cameroon	Hôpital de district Okola	Okola
Cameroon	Hôpital de district Olembe	Olembe
Cameroon	Hôpital de district St Jean de Malte	Penja
Cameroon	Hôpital de district Yoko	Yoko
Uganda	Ishongororo HC IV	Ibanda
Uganda	Ruhoko HC IV	Ibanda
Uganda	Kabwohe Clinical Research Center HC II	Kabwohe
Uganda	Kabwohe HC IV	Kabwohe
Uganda	Kitagata Hospital	Kitagata
Uganda	Bubaare HC III	Mbarara
Uganda	Bwizibwera HC IV	Mbarara
Uganda	Kakoba HC III	Mbarara
Uganda	Mbarara Municipal Council HC IV	Mbarara
Uganda	Bwongyera HC III	Ntungamo
Uganda	Itojo Hospital	Ntungamo
Uganda	Kitwe HC IV	Ntungamo
Uganda	Ntungamo Ngoma HC III	Ntungamo
Uganda	Rubaare HC IV	Ntungamo
Uganda	Rwashamaire HC IV	Ntungamo

Sponsors (4)

Lead Sponsor	Collaborator
Elizabeth Glaser Pediatric AIDS Foundation	Epicentre, Institut de Recherche pour le Developpement, University of Sheffield

Countries where clinical trial is conducted

Cameroon,  Uganda, 

References & Publications (7)

Egere U, Sillah A, Togun T, Kandeh S, Cole F, Jallow A, Able-Thomas A, Hoelscher M, Heinrich N, Hill PC, Kampmann B. Isoniazid preventive treatment among child contacts of adults with smear-positive tuberculosis in The Gambia. Public Health Action. 2016 Dec 21;6(4):226-231. doi: 10.5588/pha.16.0073. — View Citation

Graham SM. The management of infection with Mycobacterium tuberculosis in young children post-2015: an opportunity to close the policy-practice gap. Expert Rev Respir Med. 2017 Jan;11(1):41-49. doi: 10.1080/17476348.2016.1267572. Epub 2016 Dec 10. — View Citation

Mandalakas AM, Hesseling AC, Gie RP, Schaaf HS, Marais BJ, Sinanovic E. Modelling the cost-effectiveness of strategies to prevent tuberculosis in child contacts in a high-burden setting. Thorax. 2013 Mar;68(3):247-55. doi: 10.1136/thoraxjnl-2011-200933. Epub 2012 Jun 20. — View Citation

Mandalakas AM, Kirchner HL, Walzl G, Gie RP, Schaaf HS, Cotton MF, Grewal HM, Hesseling AC. Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting. Am J Respir Crit Care Med. 2015 Apr 1;191(7):820-30. doi: 10.1164/rccm.201406-1165OC. — View Citation

Rutherford ME, Hill PC, Triasih R, Sinfield R, van Crevel R, Graham SM. Preventive therapy in children exposed to Mycobacterium tuberculosis: problems and solutions. Trop Med Int Health. 2012 Oct;17(10):1264-73. doi: 10.1111/j.1365-3156.2012.03053.x. Epub 2012 Aug 5. — View Citation

Szkwarko D, Hirsch-Moverman Y, Du Plessis L, Du Preez K, Carr C, Mandalakas AM. Child contact management in high tuberculosis burden countries: A mixed-methods systematic review. PLoS One. 2017 Aug 1;12(8):e0182185. doi: 10.1371/journal.pone.0182185. eCollection 2017. — View Citation

Triasih R, Robertson CF, Duke T, Graham SM. A prospective evaluation of the symptom-based screening approach to the management of children who are contacts of tuberculosis cases. Clin Infect Dis. 2015 Jan 1;60(1):12-8. doi: 10.1093/cid/ciu748. Epub 2014 Sep 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Proportion of children eligible for PT	Number of children eligible for PT among screened children	6 months
Secondary	Proportion of children started on PT	Number of children started on PT among those eligible for PT	6 months
Secondary	Proportion of children who did not complete PT	Number of children who did not complete PT among those started on PT	6 months
Secondary	Proportion of children with presumptive TB	Number of children with symptoms suggestive of TB among screened children (< 15 years)	1 month
Secondary	Proportion of children investigated for TB	Number of children with presumptive TB investigated for TB	1 month
Secondary	Proportion of children diagnosed with TB	Number of children diagnosed with TB among those with symptoms suggestive of TB	1 month
Secondary	Proportion of children started on TB treatment	Number of children with TB diagnosis who are started on TB treatment	1 month
Secondary	Proportion of adult contacts screened	Number of adult contacts screened among household identified adult contacts	1 month
Secondary	Proportion of adults presumptive TB cases	Number of adults with symptoms suggestive of TB among those screened for TB	1 month
Secondary	Proportion of adults diagnosed with TB	Number of adults presumptive TB cases diagnosed with TB	1 month
Secondary	Proportion of children with serious adverse events	Number of children with serious adverse events among children started on PT	6 months
Secondary	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
Secondary	Treatment adherence	Ratio of PT dose taken by the child over the total number of doses prescribed	6 months
Secondary	Treatment outcomes of children started on TB treatment	Cured; Treatment completed; Failure; Death; Lost to follow up; Transferred out	6 months
Secondary	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
Secondary	TB case detection during pre-intervention period	Number of patients registered in the facility TB register one year before intervention	2 years
Secondary	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
Secondary	TB treatment outcome of registered TB patients during pre-intervention period	Cured; Treatment completed; Failure; Death; Lost to follow up; Transferred out	2 years
Secondary	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
Secondary	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
Secondary	Number of household visits by CHW	Number of visits by the CHW to the household for contact screening per household	2 years
Secondary	Proportion of parents/guardians who accept household visit	Acceptability of household visit for contact screening	2 years
Secondary	Reasons of refusal of household visit	Description of screening failures	2 years
Secondary	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
Secondary	Critical events experienced by CHW during household visit	Description of critical events during house visit and how these where dealt with	2 years
Secondary	Transport cost for household visit by CHW	Cost of transportation for the CHW to go from the health facility to a household	2 years
Secondary	Transport cost for parents/guardian for facility-based screening	Cost supported by families to bring child contact to the facility for screening	2 years
Secondary	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
Secondary	Proportion of delivered activities compared to the intended activities of the model	This outcome will assess fidelity to study procedures	2 years