The DECIDE-TB Trial; Validation of Treatment Decision Algorithms for Childhood Tuberculosis

NCT ID: NCT06593080

Last Updated: 2024-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

30240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-01

Study Completion Date

2027-03-31

Brief Summary

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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

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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.

Conditions

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Tuberculosis Child Health HIV Severe Acute Malnutrition

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Stepped Wedge Design
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Standard of Care

The District Hospitals and Primary Health Centres in study districts will implement TB diagnosis for children as per the current Standard of Care (control) in both countries . In Mozambique, the SOC is based on local algorithms which include: TB symptoms screening (TB contact history), HIV testing, Xpert testing on induced sputum (and stool), and a tuberculin skin test. Urine Lipoarabinomannan (LAM) is indicated for Children Living with HIV (CLHIV). No CXR is performed.

In Zambia, the SOC is based on the Union desk guide algorithm which includes: TB symptom screening (TB contact history), HIV testing and Xpert testing on respiratory or stool samples. Urine LAM is indicated for CLHIV,Severe Acute Malnutrition, sepsis, immune-suppression; chronic kidney diseases and cancer. CXRs are performed depending on the facilities. Other tests and imaging are advised in presumed extrapulmonary TB cases. A confirmed TB diagnosis is made based on a positive Xpert or LAM test.

Group Type NO_INTERVENTION

No interventions assigned to this group

The comprehensive TDA based approach

Children will benefit from the country SOC as described in the control arm, plus the study intervention

Group Type EXPERIMENTAL

The comprehensive TDA based approach

Intervention Type OTHER

The intervention consists of implementing a comprehensive TDA-based approach for TB diagnosis and treatment decision-making, including shorter treatment for non-severe TB in children identified as TB presumptive cases through a CDSS. It will also include the management of high-risk groups. In practice, all sick children will be assessed using the WHO-suggested TDAs A with CXR (DH) and B without CXR (PHC). CLHIV and those hospitalised with SAM at DH will have further assessment and treatment decisions based on the PAANTHER and TB-Speed SAM TDAs, respectively.

Clinical and microbiological assessment data will be incorporated into a CDSS to help with the clinical decision to initiate TB treatment. The CDSS will incorporate specific features and test results for high-risk group children based on the PAANTHER TDA and the TB-Speed SAM TDA and will incorporate the results of the severity assessment to guide the choice of TB treatment duration once children are diagnosed with TB.

Interventions

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The comprehensive TDA based approach

The intervention consists of implementing a comprehensive TDA-based approach for TB diagnosis and treatment decision-making, including shorter treatment for non-severe TB in children identified as TB presumptive cases through a CDSS. It will also include the management of high-risk groups. In practice, all sick children will be assessed using the WHO-suggested TDAs A with CXR (DH) and B without CXR (PHC). CLHIV and those hospitalised with SAM at DH will have further assessment and treatment decisions based on the PAANTHER and TB-Speed SAM TDAs, respectively.

Clinical and microbiological assessment data will be incorporated into a CDSS to help with the clinical decision to initiate TB treatment. The CDSS will incorporate specific features and test results for high-risk group children based on the PAANTHER TDA and the TB-Speed SAM TDA and will incorporate the results of the severity assessment to guide the choice of TB treatment duration once children are diagnosed with TB.

Intervention Type OTHER

Eligibility Criteria

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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
Maximum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Bordeaux

OTHER

Sponsor Role collaborator

Instituto Nacional de Saúde, Mozambique

OTHER_GOV

Sponsor Role collaborator

ADERA

UNKNOWN

Sponsor Role collaborator

University of Stellenbosch

OTHER

Sponsor Role collaborator

Imperial College London

OTHER

Sponsor Role collaborator

Institut de Recherche pour le Développement (IRD)

UNKNOWN

Sponsor Role collaborator

University of Sheffield

OTHER

Sponsor Role collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role collaborator

Ministry of Health, Zambia

OTHER_GOV

Sponsor Role collaborator

Ministry of Health, Mozambique

OTHER_GOV

Sponsor Role collaborator

Eduardo Mondlane University

OTHER

Sponsor Role collaborator

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role collaborator

Chishala Chabala

OTHER

Sponsor Role lead

Responsible Party

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Chishala Chabala

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Olivier Marcy

Role: PRINCIPAL_INVESTIGATOR

University of Bordeaux

Chishala Chabala

Role: PRINCIPAL_INVESTIGATOR

University of Zambia

Joanna Orne-Gliemann

Role: PRINCIPAL_INVESTIGATOR

University of Bordeaux

James Seddon

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

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Chawama Urban Health Centre

Chingola, Copperbelt, Zambia

Site Status RECRUITING

Chiwempala Urban Health Centre

Chingola, Copperbelt, Zambia

Site Status RECRUITING

Kabundi East Urban Health Clinic

Chingola, Copperbelt, Zambia

Site Status RECRUITING

Kasompe Urban Health Centre

Chingola, Copperbelt, Zambia

Site Status RECRUITING

Muchinshi Rural Health Centre

Chingola, Copperbelt, Zambia

Site Status RECRUITING

Nchanga 1 Urban Health Centre

Chingola, Copperbelt, Zambia

Site Status RECRUITING

Nchanga North Referal Hospital

Chingola, Copperbelt, Zambia

Site Status RECRUITING

Allessandras Urban Health Centre

Luanshya, Copperbelt, Zambia

Site Status RECRUITING

Chaisa Urban Health Centre

Luanshya, Copperbelt, Zambia

Site Status RECRUITING

Fisenge Urban Health Centre

Luanshya, Copperbelt, Zambia

Site Status RECRUITING

Kawama Urban Health Centre

Luanshya, Copperbelt, Zambia

Site Status RECRUITING

Malaika Urban Health Centre

Luanshya, Copperbelt, Zambia

Site Status RECRUITING

Mikomfwa Urban Health Centre

Luanshya, Copperbelt, Zambia

Site Status RECRUITING

Roan Antelope General Hospital

Luanshya, Copperbelt, Zambia

Site Status RECRUITING

Thomson District Hospital

Luanshya, Copperbelt, Zambia

Site Status RECRUITING

Chipepo Rural Health Centre

Chirundu, Southern Province, Zambia

Site Status RECRUITING

Hachipilika Rural Health Centre

Chirundu, Southern Province, Zambia

Site Status RECRUITING

Jamba Rural Health Centre

Chirundu, Southern Province, Zambia

Site Status RECRUITING

Kapululira Rural Health Centre

Chirundu, Southern Province, Zambia

Site Status RECRUITING

Lusitu Rural Health Centre

Chirundu, Southern Province, Zambia

Site Status RECRUITING

Mtendere Mission Referal hospital

Chirundu, Southern Province, Zambia

Site Status RECRUITING

Sikoongo Rural Health Centre

Chirundu, Southern Province, Zambia

Site Status RECRUITING

Habulile Rural Health Centre

Kalomo, Southern Province, Zambia

Site Status RECRUITING

Kalomo District Hospital

Kalomo, Southern Province, Zambia

Site Status RECRUITING

Kalomo Urban Health Centre

Kalomo, Southern Province, Zambia

Site Status RECRUITING

Mawaya Urban Health Centre

Kalomo, Southern Province, Zambia

Site Status RECRUITING

Namwianga Urban Health Centre

Kalomo, Southern Province, Zambia

Site Status RECRUITING

Nkandanzovu Rural Health Centre

Kalomo, Southern Province, Zambia

Site Status RECRUITING

Siachitema Rural Health Centre

Kalomo, Southern Province, Zambia

Site Status RECRUITING

Countries

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Zambia

Central Contacts

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Clementine Roucher

Role: CONTACT

+330557574723 ext. 330

Natasha Namuziya

Role: CONTACT

+26021250753 ext. 260

Facility Contacts

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Alan Kachuka

Role: primary

Natasha Namuziya

Role: backup

Chishala Chabala

Role: backup

Other Identifiers

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DECIDE-TB

Identifier Type: -

Identifier Source: org_study_id

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