Impact of Systematic Early Tuberculosis Detection Using Xpert MTB/RIF Ultra in Children With Severe Pneumonia in High Tuberculosis Burden Countries
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 2,570
- 试验地点
- 32
- 主要终点
- All-cause mortality 12 weeks after inclusion
研究概览
简要总结
Despite progress in reducing tuberculosis (TB) incidence and mortality in the past 20 years, TB is a top ten cause of death in children under 5 years worldwide. However, childhood TB remains massively underreported and undiagnosed, mostly because of the challenges in confirming its diagnosis due to the paucibacillary nature of the disease and the difficulty in obtaining expectorated sputum in children.
Pneumonia is the leading cause of death in children under the age of 5 years worldwide. There is growing evidence that, in high TB burden settings, TB is common in children with pneumonia, with up to 23% of those admitted to hospital with an initial diagnosis of pneumonia later being diagnosed as TB. However, the current World Health Organization (WHO) standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. Hence, TB is often under-diagnosed or diagnosed late in children presenting with pneumonia.
In this context, the investigators are proposing to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra, performed on NPAs and stool samples, to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples.
TB-Speed Pneumonia is a multicentric, stepped wedge diagnostic trial conducted in six countries with high TB incidence: Cote d'Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia.
The sub-study on Covid-19 will assess the prevalence and impact of the Covid-19 in young children hospitalized with severe pneumonia. The sub-study findings are expected to guide policy makers and clinicians on potential specific screening and management measures for these vulnerable groups of children. They are also key to analysing TB-Speed Pneumonia results on mortality in a context of the Covid-19 outbreak and to take into consideration SARS-CoV-2 infection status in the main study analysis.
详细描述
Pneumonia is the leading cause of death in children under the age of 5 years worldwide.
There is growing evidence that, in high TB burden settings, TB is common in children with pneumonia, with up to 23% of those admitted to hospital with an initial diagnosis of pneumonia later being diagnosed as TB]. This is particularly true in the African and Asian WHO regions, which accounted for 30% and 35% of all paediatric TB cases in 2016 respectively.
In these regions, the case fatality rate for childhood pneumonia associated with TB is high, ranging from 4% to 21% [8], with younger age, malnutrition and HIV infection increasing the risk of death.
The current standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. Hence, TB is often under-diagnosed or diagnosed late in children presenting with pneumonia. Although TB is a chronic disease in adults, recent data show that the duration of respiratory symptoms before admission can be acute in children with severe pneumonia associated with TB [8]. Hence, Identifying TB cases early and shortening the diagnostic delay to initiate appropriate TB treatment in children with clinical presentation of severe acute pneumonia is likely to reduce mortality.
An improved molecular diagnostic tool for paediatric TB:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 2 Months 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 2 to 59 months
- •Newly hospitalized for severe pneumonia defined using WHO criteria as cough or difficulty in breathing with:
- •Peripheral oxygen saturation < 90% or central cyanosis, or
- •Severe respiratory distress (e.g. grunting, nasal flaring, very severe chest indrawing), or
- •Signs of pneumonia, defined as cough or difficulty in breathing with fast breathing (tachypnea) and/or chest indrawing, with any of the following danger signs:
- •Inability to breastfeed or drink,
- •Persistent vomiting
- •Lethargy or reduced level of consciousness
- •Convulsions,
- •Stridor in calm child
- •Severe malnutrition
- •Informed consent signed by parent/guardian
排除标准
- •- Ongoing TB treatment or history of intake of anti-TB drugs in the last 6 months
结局指标
主要结局
All-cause mortality 12 weeks after inclusion
时间窗: 12 weeks
次要结局
- • Proportion of children with TB treatment initiated at any time during follow-up(12 weeks)
- Number of children diagnosed with TB at 12 weeks(12 weeks)
- • Time to TB treatment initiation(12 weeks)
- • Duration of TB treatment at end of trial(12 weeks)
- • Number of inpatient deaths(12 weeks)
- • Duration of initial hospitalization(12 weeks)
- • Number of readmissions following discharge(12 weeks)
- • Weight gain at 12 weeks(12 weeks)
- • Proportion of NPA and stool samples with positive TB detection using Ultra•(12 weeks)
- • Proportion of Ultra-confirmed and clinically-diagnosed TB cases(12 weeks)
- • Feasibility of NPA and stool samples collection (1)(12 weeks)
- • Feasibility of NPA and stool samples collection (2)(12 weeks)
- • Safety of NPA collection(12 weeks)
- • Tolerability of NPA specimen collection procedures assessed by the child(Hospital admission)
- • Tolerability of NPA specimen collection procedures assessed by the parents(Hospital admission)
- • Tolerability of NPA specimen collection procedures assessed by the nurses(Hospital admission)
- • Acceptability of NPA and stool specimen collection procedures(Hospital admission)
- To assess the prevalence of Covid-19 (confirmed and probable cases) in children below 5 years admitted with WHO-defined severe pneumonia(12 weeks)
- Number of inpatients death in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(12 weeks)
- Weight gain in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(12 weeks)
- Inability to breastfeed or drink in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(At hospital discharge, estimated average = 7 days)
- Duration of initial hospitalization in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(12 weeks)
- Number of readmissions following discharge in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(12 weeks)
- Lethargy or reduced level of consciousness in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(At hospital discharge, estimated average = 7 days)
- Convulsions in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(At hospital discharge, estimated average = 7 days)
- Stridor in calm child in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(At hospital discharge, estimated average = 7 days)
- Oxygen saturation < 90% in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(At hospital discharge, estimated average = 7 days)
- Central cyanosis in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(At hospital discharge, estimated average = 7 days)
- Grunting in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(At hospital discharge, estimated average = 7 days)
- Nasal flaring in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(At hospital discharge, estimated average = 7 days)
- Chest in-drawing in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children)(At hospital discharge, estimated average = 7 days)
- To describe the laboratory characteristics (CRP) of Covid-19 cases(12 weeks)
- To describe the laboratory characteristics (full blood count) of Covid-19 cases(12 weeks)
- Description by type and frequency of the signs of viral pneumonia on CXR with interstitial changes of Covid-19 cases(12 weeks)
- To assess the yield of stool as compared to nasal swab for the detection of the SARS-CoV-2 by real time reverse transcription-polymerase chain reaction (RT-PCR)(12 weeks)
- Number of children having a PCR positive for respiratory syncytial virus(12 weeks)
- To assess seroprevalence and seroconversion (immunoglobulin M and immunoglobulin G to SARS-CoV-2) at Day 0 and Month 3(12 weeks)