Clinical trial NCT04038632: Impact of an Innovative Childhood TB Diagnostic Approach Decentralized to District Hospital and Primary Health Care Levels on Childhood Tuberculosis Case Detection and Management in High Tuberculosis Incidence Countries (TB-Speed Decentralisation)
Official title: Impact of an Innovative Childhood TB Diagnostic Approach Decentralized to District Hospital and Primary Health Care Levels on Childhood Tuberculosis Case Detection and Management in High Tuberculosis Incidence Countries
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis in Children
Keywords: Decentralized Diagnosis approaches
Childhood TB
Case detection
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: UNITAID
First posted: 2019-07-31
Enrollment: 3106
Sex: ALL
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will comprise an observation phase, during which there will be no interference with the routine TB childhood diagnosis processes, followed by an intervention phase in participating districts. During the last month of the observation phase, each district will be randomly assigned to implement either DH or PHC focused decentralisation. There will be no individual patient level randomisation.

The study will also include a nested cohort at both the DH and PHC during the intervention phase for a selected sub-set of children with presumptive TB and all children with a diagnosis of TB who consent to participate. This prospective cohort will enable to further document study endpoints related to follow up (TB treatment outcome) and to document TB diagnosis by assessing spontaneous resolution or resolution under TB treatment
Primary purpose: DIAGNOSTIC

Brief summary: The TB-Speed Decentralisation study aims to increase childhood Tuberculosis (TB) case detection at district hospital (DH) and Primary health Care (PHC) levels using adapted and child-friendly specimen collection methods, i.e. Nasopharyngeal Aspirate (NPA) and stool samples, sensitive microbiological detection tests (Ultra) close to the point-of-care (Omni/G1(Edge)), reinforced training on clinical diagnosis, and standardized CXR quality and interpretation using digital radiography.

The TB-Speed Decentralisation study will evaluate the impact of an innovative patient care level diagnostic approach deployed at DH and PHC levels, namely the DH focused and the PHC focused decentralization strategies. This is aimed at, improving case detection in 6 high TB incidence in low/moderate resource countries: Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone, and Uganda, and compare effectiveness and cost-effectiveness of the two different decentralization approaches.

The hypothesis is that, in countries with high and very high TB incidence (100-299 and ≥300 cases/100,000 population/year, respectively), a systematic approach to the screening for and diagnosis of TB in sick children presenting to the health system will increase childhood TB case detection, especially PTB, which represents the majority of the disease burden (\>75% of case). The study also hypothesizes that sputum collection using battery-operated suction machines and microbiological TB diagnosis using Omni/G1 (Edge) can be decentralized to PHC level, thus enabling TB diagnosis and treatment in children at PHC level.

Detailed description: This will be an operational research study using:

* a before and after cross-sectional design to assess the impact of decentralizing an innovative childhood TB diagnostic approach
* a cross-sectional and nested cohort design to compare two different decentralization strategies at DH and PHC levels.
* quantitative and qualitative methods The intervention will be at two levels: at patient care level where an innovative childhood TB diagnostic approach will be implemented, and at health systems level where two distinct decentralization strategies will be implemented. The patient care level TB diagnostic approach consists of systematic TB screening, clinical evaluation, NPA and stool or sputum testing using Xpert Ultra, and optimised CXR reading. The two decentralization strategies are the DH-focused and the PHC-focused implementation of the innovative childhood TB diagnostic approach. Two districts per participating countries will be randomly assigned to implement the DH or PHC-focused strategies.

The study will also include a nested cohort at both the DH and PHC during the intervention phase for a selected sub-set of children with presumptive TB and all children with a diagnosis of TB that consent to participate. This prospective cohort will enable to further document study endpoints related to follow up (TB treatment outcome) and to document TB diagnosis by assessing spontaneous resolution or resolution under TB treatment.

The study will comprise an observation phase followed by an intervention phase in participating districts. During the last month of the observation phase, each district will be randomly assigned to implement either DH or PHC-focused decentralisation. There will be no patient level randomisation.

During this 3-month observation phase, the study will 1) describe the childhood TB diagnosis data and practices; 2) describe the referral processes and outcomes of referrals for TB diagnosis and treatment where feasible and 3) assess existing challenges in childhood TB diagnosis and treatment, as well as readiness (including potential challenges) for the study intervention implementation. There will be no interference with the routine TB childhood diagnosis processes.

Mixed-methods (quantitative and qualitative) will be used including the collection of retrospective and prospective aggregated data by study nurses from facility registers, the implementation of a self-administered questionnaire among all healthcare workers (HCWs), the observation of consultations and care provided, and the conduct of individual interviews with HCWs and key informants.

At the beginning of the intervention phase, a 3-months preparation period will set up the health facilities for decentralization by providing equipment, materials, and reagents, training health workers in childhood TB care, in NPA and stool collection and testing on Ultra, setting up G1 (Edge) at PHC or G4 at DH if not already available and digital CXR and CXR quality control. Existing health care workers will be trained in childhood TB care according to the National Tuberculosis Program (NTP) guidelines, and also in NPA and stool collection and testing on Ultra for study purposes.

Implementation of the innovative childhood TB diagnostic approach at the selected DH and PHC will start as soon as sites are equipped and HCWs trained in childhood TB care and NPA and stool collection, and will implement continued capacity building at sites, regular clinical mentoring visits with NTP or their representative, and continued CXR quality control.

The 6-month prospective cohort follow-up study will be initiated immediately and will consecutively include every tenth child with presumptive TB and all children diagnosed with TB.

Individual data collection will be initiated as soon as the innovative childhood TB diagnostic approach including NPA and stool sample collection and Ultra testing is implemented in the site and will be conducted throughout the intervention phase to document secondary endpoints. Aggregated data for TB screening will be collected throughout the study.

Feasibility, acceptability, and compliance to the intervention protocol will be assessed by mixed methods including a repeat self-administered questionnaire among all HCWs, observations of consultations and care provided, and individual interviews with HCWs, National TB program \& local health authorities representatives, and beneficiaries. i.e. parents/guardians.

Eligibility criteria: Inclusion Criteria:

* Sick children seeking care at Oupatient Department of District Hospital or Primary Health Center
* Age \<15 years

Exclusion Criteria:

- None

Primary outcomes:
measure: Children diagnosed with TB
timeFrame: Day 0
Secondary outcomes:
measure: TB case detection
timeFrame: Month 6
measure: TB screening in outpatient children - 1
timeFrame: Day 7
measure: TB screening in outpatient children - 2
timeFrame: Day 7
measure: Feasibility of implementing the different diagnostic approach components - 1
timeFrame: Day 7
measure: Feasibility of implementing the different diagnostic approach components - 2
timeFrame: Day 7
measure: Feasibility of implementing the different diagnostic approach components - 3
timeFrame: Day 7
measure: TB treatment uptake and time to TB treatment initiation - 1
timeFrame: Month 6
measure: TB treatment uptake and time to TB treatment initiation - 2
timeFrame: Month 6
measure: Cost-effectiveness from the health services perspective
timeFrame: Month 22
measure: Acceptability by health care providers, NTPs and health authorities, and beneficiaries
timeFrame: Day 0
measure: Fidelity of the implementation of the diagnostic approach as compared to the protocol and study procedures - 1
timeFrame: Month 6
measure: Fidelity of the implementation of the diagnostic approach as compared to the protocol and study procedures - 2
timeFrame: Month 22
measure: Performance of the diagnostic approach at patient level
timeFrame: Month 6
measure: TB treatment outcome
timeFrame: Month 6
measure: Diagnostic performance of CXR reading by clinicians at DH and PHC levels
timeFrame: Month 6
measure: Added value of CXR in the diagnosis of TB in children as compared to microbiology and clinical evaluation only
timeFrame: Month 6
measure: Uptake of the quality control of the CXR reading
timeFrame: Month 6
Other outcomes:
Locations:
city: Angroka
country: Cambodia
facility: Angroka Rh
city: Angroka
country: Cambodia
facility: Taphem Hc
city: Angroka
country: Cambodia
facility: Tropang Andert Hc
city: Batheay
country: Cambodia
facility: Batheay Rh
city: Batheay
country: Cambodia
facility: Choeung Chnok Hc
city: Batheay
country: Cambodia
facility: Tumnub Hc
city: KUS
country: Cambodia
facility: KUS HC
city: Nhaeng Nhang
country: Cambodia
facility: Nhaeng Nhang Hc
city: Phaav
country: Cambodia
facility: Phaav HC
city: Sambour
country: Cambodia
facility: Sambour Hc
city: Bafia
country: Cameroon
facility: Csi Messngssang
city: Bafia
country: Cameroon
facility: HD BAFIA
city: Balamba
country: Cameroon
facility: Csi Balamba Bafia
city: Batchenga
country: Cameroon
facility: Cma Batchenga
city: Bokito
country: Cameroon
facility: Cma Bokito Bafia
city: Essong
country: Cameroon
facility: Csi Essong
city: Kiiki
country: Cameroon
facility: Cma Kiiki Bafia
city: Obala
country: Cameroon
facility: Cma Fomakap
city: Obala
country: Cameroon
facility: Csi Ngogo
city: Obala
country: Cameroon
facility: Obala Hosp
city: Banteapleu
country: Côte D'Ivoire
facility: Dr Banteapleu
city: Dakpadou
country: Côte D'Ivoire
facility: Csu Dakpadou
city: Daleu
country: Côte D'Ivoire
facility: Csr Daleu
city: Danane
country: Côte D'Ivoire
facility: H G de Danane
city: Kouan-houle
country: Côte D'Ivoire
facility: Csu Kouan-Houle
city: Mahapleu
country: Côte D'Ivoire
facility: Csu Mahapleu
city: Medon
country: Côte D'Ivoire
facility: Csr Medon
city: Sago
country: Côte D'Ivoire
facility: CMS SAGO
city: Sahoua
country: Côte D'Ivoire
facility: Dr de Sahoua
city: Sassandra
country: Côte D'Ivoire
facility: H G Sassandra
city: Chiaquelane
country: Mozambique
facility: Chiaquelane
city: Chibonzane
country: Mozambique
facility: Chibonzane
city: Chidenguele
country: Mozambique
facility: Chidenguele
city: Chokwe
country: Mozambique
facility: Chalocuane
city: Chokwe
country: Mozambique
facility: HOKWE
city: Chokwe
country: Mozambique
facility: Hosp Rural Chokwe
city: Macuacua
country: Mozambique
facility: MACUACUA
city: Manjacaze
country: Mozambique
facility: Hospital Rural de Manjacaze
city: Manjacaze
country: Mozambique
facility: Laranjeira
city: Babara
country: Sierra Leone
facility: Babara Chc
city: BO
country: Sierra Leone
facility: Bo Govt Hosp
city: BO
country: Sierra Leone
facility: New Police barracks
city: Gbinti
country: Sierra Leone
facility: Gbinti Chc
city: Gerihun
country: Sierra Leone
facility: Gerihun Chc
city: Koribondo
country: Sierra Leone
facility: Koribondo Chc
city: Mange
country: Sierra Leone
facility: Mange Chc
city: Njala
country: Sierra Leone
facility: Njala University Chc
city: Petifu
country: Sierra Leone
facility: Petifu Chc
city: Port Loko
country: Sierra Leone
facility: Port Loko Govt Hosp
city: Buyamba
country: Uganda
facility: Buyamba Hc Iii
city: Kambuga
country: Uganda
facility: Kambuga Hospital
city: Kanungu
country: Uganda
facility: Kanungu Hciv
city: Kanyantorogo
country: Uganda
facility: Kanyantorogo Hciii
city: Lwamaggwa
country: Uganda
facility: Lwamaggwa Hc Iii
city: Lwanda
country: Uganda
facility: Lwanda Hc Iii
city: Manya
country: Uganda
facility: St Bernards Manya Hc Iii
city: Matanda
country: Uganda
facility: Matanda Hciii
city: Nyamirama
country: Uganda
facility: Nyamirama HC III
city: Rakai
country: Uganda
facility: Rakai Hospital
Study officials:
affiliation: University of Bordeaux
name: Olivier Marcy, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de Recherche pour le Developpement
name: Maryline Bonnet, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: MU-JHU Care Ltd
name: Eric Wobudeya, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Joshi B, De Lima YV, Massom DM, Kaing S, Banga MF, Kamara ET, Sesay S, Borand L, Taguebue JV, Moh R, Khosa C, Breton G, Mwanga-Amumpaire J, Bonnet M, Wobudeya E, Marcy O, Orne-Gliemann J; TB-Speed Decentralization study group. Acceptability of decentralizing childhood tuberculosis diagnosis in low-income countries with high tuberculosis incidence: Experiences and perceptions from health care workers in Sub-Saharan Africa and South-East Asia. PLOS Glob Public Health. 2023 Oct 11;3(10):e0001525. doi: 10.1371/journal.pgph.0001525. eCollection 2023.