Clinical trial NCT03832023: Community-based Tuberculosis Tracing and Preventive Therapy
Official title: Community Intervention for Tuberculosis Active Contact Tracing and Preventive Therapy - a Cluster Randomized Study (CONTACT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis
Keywords: Children
Contact tracing
Preventive therapy
Prophylaxis
Community health workers
Community-based distribution
Standard of care
Screening
Randomized controlled trial
Cameroon
Uganda
Patient outcome assessment
Lead sponsor: Elizabeth Glaser Pediatric AIDS Foundation
Sponsor class: OTHER
Collaborators: name: Epicentre
name: University of Sheffield
name: Institut de Recherche pour le Developpement
First posted: 2019-02-06
Enrollment: 1400
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: HEALTH_SERVICES_RESEARCH

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:

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.

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

Primary outcomes:
measure: Completion of preventive therapy
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of children screened
timeFrame: 6 months
measure: Proportion of children eligible for PT
timeFrame: 6 months
measure: Proportion of children started on PT
timeFrame: 6 months
measure: Proportion of children who did not complete PT
timeFrame: 6 months
measure: Proportion of children with presumptive TB
timeFrame: 1 month
measure: Proportion of children investigated for TB
timeFrame: 1 month
measure: Proportion of children diagnosed with TB
timeFrame: 1 month
measure: Proportion of children started on TB treatment
timeFrame: 1 month
measure: Proportion of adult contacts screened
timeFrame: 1 month
measure: Proportion of adults presumptive TB cases
timeFrame: 1 month
measure: Proportion of adults diagnosed with TB
timeFrame: 1 month
measure: Proportion of children with serious adverse events
timeFrame: 6 months
measure: Proportion of children with adverse event of interest
timeFrame: 6 months
measure: Treatment adherence
timeFrame: 6 months
measure: Treatment outcomes of children started on TB treatment
timeFrame: 6 months
measure: Proportion of children diagnosed with TB
timeFrame: 6 months
measure: TB case detection during pre-intervention period
timeFrame: 2 years
measure: Proportion of children among all registered TB cases during pre-intervention period
timeFrame: 2 years
measure: TB treatment outcome of registered TB patients during pre-intervention period
timeFrame: 2 years
measure: Number of children started on PT during pre-intervention period
timeFrame: 2 years
measure: Completion rate of children started on PT intervention during pre-intervention period
timeFrame: 2 years
measure: Number of household visits by CHW
timeFrame: 2 years
measure: Proportion of parents/guardians who accept household visit
timeFrame: 2 years
measure: Reasons of refusal of household visit
timeFrame: 2 years
measure: Preference for household visit versus facility visit
timeFrame: 2 years
measure: Critical events experienced by CHW during household visit
timeFrame: 2 years
measure: Transport cost for household visit by CHW
timeFrame: 2 years
measure: Transport cost for parents/guardian for facility-based screening
timeFrame: 2 years
measure: Time spent to perform household contact screening visit
timeFrame: 2 years
measure: Proportion of delivered activities compared to the intended activities of the model
timeFrame: 2 years
Other outcomes:
Locations:
city: Bonabéri
country: Cameroon
facility: Hôpital de district Bonassama
city: Douala
country: Cameroon
facility: Hôpital de district Log-Baba
city: Edéa
country: Cameroon
facility: Centre Médical d'arrondissement Delangue
city: Mbalmayo
country: Cameroon
facility: Hôpital de district Mbalmayo
city: Mfou
country: Cameroon
facility: Hôpital de district Mfou
city: Nkongsamba
country: Cameroon
facility: Hôpital régional Nkongsamba
city: Okola
country: Cameroon
facility: Hôpital de district Okola
city: Olembe
country: Cameroon
facility: Hôpital de district Olembe
city: Penja
country: Cameroon
facility: Hôpital de district St Jean de Malte
city: Yoko
country: Cameroon
facility: Hôpital de district Yoko
city: Ibanda
country: Uganda
facility: Ishongororo HC IV
city: Ibanda
country: Uganda
facility: Ruhoko HC IV
city: Kabwohe
country: Uganda
facility: Kabwohe Clinical Research Center HC II
city: Kabwohe
country: Uganda
facility: Kabwohe HC IV
city: Kitagata
country: Uganda
facility: Kitagata Hospital
city: Mbarara
country: Uganda
facility: Bubaare HC III
city: Mbarara
country: Uganda
facility: Bwizibwera HC IV
city: Mbarara
country: Uganda
facility: Kakoba HC III
city: Mbarara
country: Uganda
facility: Mbarara Municipal Council HC IV
city: Ntungamo
country: Uganda
facility: Bwongyera HC III
city: Ntungamo
country: Uganda
facility: Itojo Hospital
city: Ntungamo
country: Uganda
facility: Kitwe HC IV
city: Ntungamo
country: Uganda
facility: Ntungamo Ngoma HC III
city: Ntungamo
country: Uganda
facility: Rubaare HC IV
city: Ntungamo
country: Uganda
facility: Rwashamaire HC IV
Study officials:
affiliation: Elisabeth Glaser Pediatric AIDS Foundation
name: Boris Tchounga, MD, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Epicentre
name: Daniel Atwine, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
citation: 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.
citation: Vasiliu A, Tiendrebeogo G, Awolu MM, Akatukwasa C, Tchakounte BY, Ssekyanzi B, Tchounga BK, Atwine D, Casenghi M, Bonnet M; CONTACT study group. Feasibility of a randomized clinical trial evaluating a community intervention for household tuberculosis child contact management in Cameroon and Uganda. Pilot Feasibility Stud. 2022 Feb 11;8(1):39. doi: 10.1186/s40814-022-00996-3.
citation: Vasiliu A, Eymard-Duvernay S, Tchounga B, Atwine D, de Carvalho E, Ouedraogo S, Kakinda M, Tchendjou P, Turyahabwe S, Kuate AK, Tiendrebeogo G, Dodd PJ, Graham SM, Cohn J, Casenghi M, Bonnet M. Community intervention for child tuberculosis active contact investigation and management: study protocol for a parallel cluster randomized controlled trial. Trials. 2021 Mar 2;22(1):180. doi: 10.1186/s13063-021-05124-9.