Validation of Treatment Decision Algorithms for Childhood Tuberculosis at District Health Care Levels in Mozambique and Zambia - the Decide-TB Cluster-randomized Pragmatic Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30,240
- 试验地点
- 29
- 主要终点
- Effectiveness endpoints: Children initiated on TB treatment
研究概览
简要总结
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.
详细描述
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:
- 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).
- 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.
- 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.
- 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.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- — 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The effectiveness assessment will be conducted using aggregated or individual data from direct beneficiaries of the intervention:
- •All sick children aged below 15 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 through community- or facility-based household contact tracing.
- •Children with presumptive TB.
- •The WHO definition of presumptive TB will be used, as defined in the 2022 WHO Operational Handbook, namely: children are classified as having presumptive TB if they have unremitting symptoms lasting more than 2 weeks (any one of cough, fever, not eating well or anorexia, weight loss or failure to thrive, fatigue, reduced playfulness or decreased activity) .
- •The definitions of presumptive TB have been adapted locally for the programmatic pilot. All children with presumptive TB as defined locally will be considered in the intervention and in secondary effectiveness and sub-group analyses.
- •High-risk group will be defined using the definition in WHO-suggested TDAs A&B as children younger than 2 years, CLHIV or children with SAM. CLHIV will be defined per national testing strategy including positive PCR test for children below the age of 18 months. Children will be considered to have SAM (and thereby be eligible for the TB-Speed SAM algorithm) using WHO criteria. These include being <5 years with a weight-for-height Z score (WHZ) < -3 SDs or mid-upper arm circumference (MUAC) < 115 mm (in children over 6 months) or clinical signs of bilateral pitting oedema, and being aged ≥5 years with a body mass index (BMI) for age Z-score < -3SD.
排除标准
- •There will be no exclusion criteria for the programmatic pilot: all children will be offered the intervention.
研究组 & 干预措施
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.
The comprehensive TDA based approach
Children will benefit from the country SOC as described in the control arm, plus the study intervention
干预措施: The comprehensive TDA based approach (Other)
结局指标
主要结局
Effectiveness endpoints: Children initiated on TB treatment
时间窗: Throughout the study, an average of 24 months
Proportion of children started on treatment for TB among sick children attending care at participant health facilities for any health complaints
次要结局
- Implementation endpoints: Fidelity(From the start of intervention to the end of the intervention, an average of 21 months)
- Health Policy endpoints: Roles, practices and processes(Throughout the study, an average of 24 months)
- Health policy endpoints: Translation mechanism(At the end of the project, after 24 months since the start of the project)
- Effectiveness endpoints: Children treated for TB among those with presumptive TB(Throughout the study, an average of 24 months)
- Effectiveness endpoints: TB treatment proportion in high-risk pediatric groups(Throughout the study, an average of 24 months)
- Effectiveness endpoints: Microbiologically confirmed TB cases(Throughout the study, an average of 24 months)
- Effectiveness endpoints: Time to TDA assessment completion(From the start of intervention to the end of the project, an average of 21 months)
- Effectiveness endpoints: Concordance of TDA results and TB treatment decisions(From the start of intervention to the end of the intervention, an average of 21 months)
- Effectiveness endpoints: Missed and over-diagnosed TB cases(From the start of intervention to the end of the intervention, an average of 21 months)
- Effectiveness endpoints: Concordance of TB severity evaluation and treatment regimen decision(From the start of intervention to the end of the intervention, an average of 21 months)
- Effectiveness endpoints: False positive and negative TB severity assessments(From the start of intervention to the end of the intervention, an average of 21 months)
- Effectiveness endpoints: Non-severe TB cases initiated on shorter treatment(From the start of intervention to the end of the intervention, an average of 21 months)
- Effectiveness endpoints: TB treatment outcomes stratified by severity and regimen duration.(From the start of intervention to the end of the intervention, an average of 21 months)
- Effectiveness endpoints: Deaths averted(From the start of intervention to the end of the intervention, an average of 21 months)
- Effectiveness endpoints: Child TB among all diagnosed TB cases, including adults(Throughout the study, an average of 24 months)
- Acceptability endpoints: Preferences(Throughout the study, an average of 24 months)
- Acceptability endpoints: Local social value (users)(Throughout the study, an average of 24 months)
- Acceptability endpoints: Local social value (beneficiaries)(Throughout the study, an average of 24 months)
- Acceptability endpoints:Health systems and socioeconomic factors(Throughout the study, an average of 24 months)
- Implementation endpoints: Feasibility(From the start of intervention to the end of the intervention, an average of 21 months)
- Implementation endpoints: Contextual factors(From the start of intervention to the end of the intervention, an average of 21 months)
- Implementation endpoints: Sustained intervention delivery(6 months post intervention)
- Health economics endpoints: Cost analysis 1(Throughout the study, an average of 24 months)
- Health economics endpoints: Cost analysis 2(Throughout the study, an average of 24 months)
- Health economics endpoints: Cost analysis 3(From the start of intervention to the end of the intervention, an average of 21 months)
- Health economics endpoints: Cost analysis 4(Throughout the study, an average of 24 months)
- Health economics endpoints: Cost effectiveness; Modelled health impact measure 1(Throughout the study, an average of 24 months)
- Health economics endpoints: Cost effectiveness; Modelled health impact measure 2(Throughout the study, an average of 24 months)
- Health economics endpoints: Cost effectiveness; Modelled health impact measure 3(Throughout the study, an average of 24 months)
- Health economics endpoints: Cost effectiveness; Modelled health impact measure 4(Throughout the study, an average of 24 months)
- Health economics endpoints: Cost effectiveness- Incremental cost 1(Throughout the study, an average of 24 months)
- Health economics endpoints: Cost effectiveness- Incremental cost 2(Throughout the study, an average of 24 months)
- Health economics endpoints: Cost effectiveness- Incremental cost 3(Throughout the study, an average of 24 months)
- Health economics endpoints: Budget impact 1(Throughout the study; an average duration of 24 months and extending up to 5 years after its conclusion.)
- Health economics endpoints: Budget impact 2(Throughout the study; an average duration of 24 months and extending up to 5 years after its conclusion.)
研究者
Chishala Chabala
Principal Investigator
University of Zambia