Clinical trial NCT06593080: The DECIDE-TB Trial; Validation of Treatment Decision Algorithms for Childhood Tuberculosis
Official title: Validation of Treatment Decision Algorithms for Childhood Tuberculosis At District Health Care Levels in Mozambique and Zambia - the Decide-TB Cluster-randomized Pragmatic Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tuberculosis
Child Health
HIV
Severe Acute Malnutrition
Lead sponsor: University of Zambia
Sponsor class: OTHER
Collaborators: name: University of Bordeaux
name: Instituto Nacional de Saúde, Mozambique
name: ADERA
name: University of Stellenbosch
name: Imperial College London
name: Institut de Recherche pour le Développement (IRD)
name: University of Sheffield
name: Ludwig-Maximilians - University of Munich
name: Ministry of Health, Zambia
name: Ministry of Health, Mozambique
name: Eduardo Mondlane University
name: European and Developing Countries Clinical Trials Partnership (EDCTP)
First posted: 2024-09-19
Enrollment: 30240
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Stepped Wedge Design
Primary purpose: DIAGNOSTIC

Brief summary: The Decide-TB project aims to generate evidence for the implementation of a comprehensive Treatment Decision Algorithms (TDA) based approach for TB in children living in high TB burden and resource-limited countries, at District Hospital (DH) and Primary Health Centre (PHC) levels, and to facilitate the integration of this evidence within practices and policies.

This programmatic pilot led by the National TB Programs (NTP) will test a TDA-based approach integrating TB screening, diagnosis, treatment decision-making, and disease severity assessment for shorter treatment eligibility, for use at a lower level of healthcare. This TDA-based approach will be evaluated in a hybrid effectiveness implementation study based on a pragmatic stepped wedge cluster-randomized trial. The Decide TB project will be implemented at the district level, targeting five districts in each country. Each cluster in a district will be made up of one district hospital and six primary health centers. The study will develop a Clinical Decision Support System (CDSS) to operationalize the use of TDAs, and strengthen District Health Information Systems (DHIS2) to collect individual data, which will contribute to monitoring and evaluation, clinical mentoring, and supervision by the country's NTPs.

Detailed description: The Decide-TB trial is a pragmatic cluster-randomized study utilizing a stepped wedge design to provide scientific evidence on a comprehensive TDA-based approach for TB screening, diagnosis, and treatment in children under 15 years at low healthcare levels in Zambia and Mozambique.

The trial's primary objective is to evaluate the effectiveness, feasibility, implementation, acceptability, costs, cost-effectiveness, and adoption of a TDA-based approach for childhood TB screening, diagnosis, and treatment decision-making under programmatic conditions at District Hospitals (DH) and Primary Health Centres (PHC) levels in these countries.

There are five specific objectives corresponding to the trial's research components:

1. To assess the effectiveness of the comprehensive TDA-based approach in increasing TB case detection in children as compared to the Standard of Care (SOC), and in providing good quality TB diagnosis and treatment decision (diagnostic accuracy and reliability of treatment decision for TB and shorter treatment).
2. To describe the implementation and the feasibility of using the comprehensive TDA-based approach, including associated digital tools, and to identify contextual determinants influencing implementation and contribute to improved implementation/adaptations throughout intervention delivery.
3. To assess preferences, acceptability, and perceived feasibility of using the comprehensive TDA-based approach, including associated digital tools, among end-users, beneficiaries, and key stakeholders.
4. To assess the costs from the health system and the beneficiary (parents/caregivers of children) perspective, the cost-effectiveness of using the comprehensive TDA-based approach, including associated digital tools, and the budget impact of scaling up the intervention.
5. To assess the factors and stakeholders that support or constrain the adoption of the comprehensive TDA-based approach as health policy at district level.

The intervention will be implemented as a programmatic pilot, following the National TB Programs' decision in Mozambique and Zambia to adopt a TDA-based approach in line with World Health Organisation's (WHO) conditional recommendations. Additionally, both the standard of care and the intervention will be implemented in a non-randomized district to document diagnostic accuracy throughout the trial. The Decide-TB trial is a hybrid effectiveness-implementation trial (type 2), assessing both the clinical intervention's effectiveness and the feasibility and utility of the implementation strategy.

Diagnostic accuracy of both the standard of care and the intervention will be evaluated in an additional district, which will transition to the intervention phase alongside the last district selected per the stepped wedge design. Aggregated data will be retrospectively collected over 12 months from all participating districts and health facilities.

The Decide-TB trial endpoints include effectiveness, acceptability, implementation, health economics, and health policy. Effectiveness endpoints include the proportion of children who started TB treatment, the time it takes to make a treatment decision, and the consistency of TDA results with final treatment decisions, among other factors. Acceptability endpoints consider user preferences and local social value, whereas implementation endpoints evaluate the practicality, fidelity, contextual aspects, and sustainability of the TDA-based method. Health economics endpoints include cost assessments, cost-effectiveness, and budget impact of scaling up the TDA-based approach vs the standard of care, while health policy endpoints look at key stakeholders' roles, practices, and policy translation processes.

Eligibility criteria: Inclusion Criteria:

* For TB screening, all symptomatic children \<16 years entering the selected health facilities (DH and PHC) at either outpatient (OPD) or inpatient (IPD) departments, including children from high-risk groups, as well as children identified as contact of TB cases.
* For access to TB diagnostic services and TDAs, children aged below 16 years identified with presumptive TB, i.e. those with ≥1 systematic screening criteria, among the following:

  * Cough with a duration of \>2 weeks,
  * Fever with a duration of \>2 weeks,
  * Documented weight loss,
  * History of TB contact with any duration of cough, OR identified by the site clinician irrespective of the above criteria, especially presumed extra-pulmonary TB cases.

Exclusion Criteria:

* Non presumptive TB cases
* Adult patients
* Patients not in the selected district or facilities

Primary outcomes:
measure: Effectiveness endpoints: Children initiated on TB treatment
timeFrame: Throughout the study, an average of 24 months
Secondary outcomes:
measure: Effectiveness endpoints: Children treated for TB among those with presumptive TB
timeFrame: Throughout the study, an average of 24 months
measure: Effectiveness endpoints: TB treatment proportion in high-risk pediatric groups
timeFrame: Throughout the study, an average of 24 months
measure: Effectiveness endpoints: Microbiologically confirmed TB cases
timeFrame: Throughout the study, an average of 24 months
measure: Effectiveness endpoints: Time to TDA assessment completion
timeFrame: From the start of intervention to the end of the project, an average of 21 months
measure: Effectiveness endpoints: Concordance of TDA results and TB treatment decisions
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Effectiveness endpoints: Missed and over-diagnosed TB cases
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Effectiveness endpoints: Concordance of TB severity evaluation and treatment regimen decision
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Effectiveness endpoints: False positive and negative TB severity assessments
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Effectiveness endpoints: Non-severe TB cases initiated on shorter treatment
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Effectiveness endpoints: TB treatment outcomes stratified by severity and regimen duration.
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Effectiveness endpoints: Deaths averted
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Effectiveness endpoints: Child TB among all diagnosed TB cases, including adults
timeFrame: Throughout the study, an average of 24 months
measure: Acceptability endpoints: Preferences
timeFrame: Throughout the study, an average of 24 months
measure: Acceptability endpoints: Local social value (users)
timeFrame: Throughout the study, an average of 24 months
measure: Acceptability endpoints: Local social value (beneficiaries)
timeFrame: Throughout the study, an average of 24 months
measure: Acceptability endpoints:Health systems and socioeconomic factors
timeFrame: Throughout the study, an average of 24 months
measure: Implementation endpoints: Feasibility
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Implementation endpoints: Fidelity
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Implementation endpoints: Contextual factors
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Implementation endpoints: Sustained intervention delivery
timeFrame: 6 months post intervention
measure: Health economics endpoints: Cost analysis 1
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Cost analysis 2
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Cost analysis 3
timeFrame: From the start of intervention to the end of the intervention, an average of 21 months
measure: Health economics endpoints: Cost analysis 4
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Cost effectiveness; Modelled health impact measure 1
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Cost effectiveness; Modelled health impact measure 2
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Cost effectiveness; Modelled health impact measure 3
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Cost effectiveness; Modelled health impact measure 4
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Cost effectiveness- Incremental cost 1
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Cost effectiveness- Incremental cost 2
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Cost effectiveness- Incremental cost 3
timeFrame: Throughout the study, an average of 24 months
measure: Health economics endpoints: Budget impact 1
timeFrame: Throughout the study; an average duration of 24 months and extending up to 5 years after its conclusion.
measure: Health economics endpoints: Budget impact 2
timeFrame: Throughout the study; an average duration of 24 months and extending up to 5 years after its conclusion.
measure: Health Policy endpoints: Roles, practices and processes
timeFrame: Throughout the study, an average of 24 months
measure: Health policy endpoints: Translation mechanism
timeFrame: At the end of the project, after 24 months since the start of the project
Other outcomes:
Locations:
city: Chingola
country: Zambia
facility: Chawama Urban Health Centre
state: Copperbelt
city: Chingola
country: Zambia
facility: Chiwempala Urban Health Centre
state: Copperbelt
city: Chingola
country: Zambia
facility: Kabundi East Urban Health Clinic
state: Copperbelt
city: Chingola
country: Zambia
facility: Kasompe Urban Health Centre
state: Copperbelt
city: Chingola
country: Zambia
facility: Muchinshi Rural Health Centre
state: Copperbelt
city: Chingola
country: Zambia
facility: Nchanga 1 Urban Health Centre
state: Copperbelt
city: Chingola
country: Zambia
facility: Nchanga North Referal Hospital
state: Copperbelt
city: Luanshya
country: Zambia
facility: Allessandras Urban Health Centre
state: Copperbelt
city: Luanshya
country: Zambia
facility: Chaisa Urban Health Centre
state: Copperbelt
city: Luanshya
country: Zambia
facility: Fisenge Urban Health Centre
state: Copperbelt
city: Luanshya
country: Zambia
facility: Kawama Urban Health Centre
state: Copperbelt
city: Luanshya
country: Zambia
facility: Malaika Urban Health Centre
state: Copperbelt
city: Luanshya
country: Zambia
facility: Mikomfwa Urban Health Centre
state: Copperbelt
city: Luanshya
country: Zambia
facility: Roan Antelope General Hospital
state: Copperbelt
city: Luanshya
country: Zambia
facility: Thomson District Hospital
state: Copperbelt
city: Chirundu
country: Zambia
facility: Chipepo Rural Health Centre
state: Southern
city: Chirundu
country: Zambia
facility: Hachipilika Rural Health Centre
state: Southern
city: Chirundu
country: Zambia
facility: Jamba Rural Health Centre
state: Southern
city: Chirundu
country: Zambia
facility: Kapululira Rural Health Centre
state: Southern
city: Chirundu
country: Zambia
facility: Lusitu Rural Health Centre
state: Southern
city: Chirundu
country: Zambia
facility: Mtendere Mission Referal hospital
state: Southern
city: Chirundu
country: Zambia
facility: Sikoongo Rural Health Centre
state: Southern
city: Kalomo
country: Zambia
facility: Habulile Rural Health Centre
state: Southern
city: Kalomo
country: Zambia
facility: Kalomo District Hospital
state: Southern
city: Kalomo
country: Zambia
facility: Kalomo Urban Health Centre
state: Southern
city: Kalomo
country: Zambia
facility: Mawaya Urban Health Centre
state: Southern
city: Kalomo
country: Zambia
facility: Namwianga Urban Health Centre
state: Southern
city: Kalomo
country: Zambia
facility: Nkandanzovu Rural Health Centre
state: Southern
city: Kalomo
country: Zambia
facility: Siachitema Rural Health Centre
state: Southern
Study officials:
affiliation: University of Bordeaux
name: Olivier Marcy
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Zambia
name: Chishala Chabala
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Bordeaux
name: Joanna Orne-Gliemann
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: James Seddon
role: PRINCIPAL_INVESTIGATOR
References: