Single-test Accuracy Study to Assess the Diagnostic Value of Faecal Calprotectin to Diagnose Necrotising Enterocolitis in Infants With Heart Defects
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 300
- 主要终点
- Faecal calprotectin
研究概览
简要总结
Necrotising enterocolitis (NEC) is a serious gut disease that can develop in infants born with cardiac defects. It causes inflammation and injury to the gut mucosa and may be life-threatening.1 The aetiology of NEC in cardiac infants is multifactorial, associated with poor cardiac outflow and poorly oxygenated systemic circulation, resulting in suboptimal blood flow to the intestines.2
Making an accurate and timely diagnosis of NEC is a significant clinical challenge.3 The clinical presentation of NEC is difficult to identify correctly in the early stages of the disease. Of concern, infants who are diagnosed with NEC at a later stage have worse disease.4 Due to the potentially life-threatening effects of NEC, clinicians who suspect a baby has NEC but are unable to confirm it, temporarily manage infants as if they have NEC as a precautionary measure.
This leads to infants without NEC having their milk feeds stopped for several days and being given unnecessary antibiotics. Compared to infants with confirmed NEC, the care of infants with suspected NEC is widely variable in terms of antibiotic regimen chosen, length of antibiotic treatment, and length of time nil-by-mouth - all these variabilities may adversely contribute to the length of hospital stay.5
We want to study a method to improve the accuracy of diagnosing NEC. We want to measure a protein marker found in babies' stools that, if combined with currently available tests (clinical features, lab tests and abdominal X-rays), 6,7 may improve the timeliness and accuracy of making a NEC diagnosis, crucially at an early stage of gut disease.
The protein marker is called calprotectin and monitoring levels in a baby's stools before and after heart surgery may help us to understand its relationship to NEC. Calprotectin is a biomarker that is released by white blood cells and is present in the gut when it is inflamed and can be measured in stool.8 The amount of calprotectin in the stool may indicate the level of gut inflammation and the presence of NEC in infants with heart defects.9
The addition of calprotectin measurement to the current routine parameters (clinical features, lab tests and abdominal X-rays) may improve the timeliness and accuracy of diagnosing NEC in infants with cardiac defects, hence improving their care pathway and outcomes.
详细描述
Why is this research important in terms of improving the health of patients? Our study will ascertain whether there is a clear relationship between levels of faecal calprotectin and the true occurrence of necrotising enterocolitis in infants with congenital heart disease. This is important because infants with congenital heart disease are burdened with feeding difficulties and poor nutrition for a range of reasons, and they can be affected by necrotising enterocolitis because of abnormal circulation of the blood to all organs, including the gut. If necrotising enterocolitis could be identified correctly in a timely way, this would help clinicians manage the nutrition of these vulnerable infants, at the same time as helping clinicians to target necrotising enterocolitis treatment to babies who truly have this condition.
Considering the different disease processes for infants with congenital heart disease to other clinical populations, such as preterm infants, it is essential to investigate calprotectin concentration in this
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An inaccurate diagnosis of NEC results in the withdrawal of an infant's milk feed, exacerbating parental stress in intensive care. Improved nutritional support has been associated with increased survival and a reduction in overall morbidity in infants with cardiac defects.10
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An inaccurate diagnosis of NEC results in the unnecessary administration of antibiotics. Antibiotics cause antibiotic-related diarrhoea, which in turn affects expected growth.11,12
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An inaccurate diagnosis of NEC results in the inappropriate use of intravenous nutrition as a substitute for enteral feeds during gut rest. Avoiding intravenous nutrition reduces the risk of line sepsis and liver disease.13
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An accurate and timely diagnosis of NEC will reduce the length of hospital stay. Infants classified with suspected NEC have a longer hospital stay.5,9
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The current per-patient marginal cost due to NEC is £13,900 and the cost due to feeding difficulties after surgery is £5,500,14, both of which could be reduced with a timely and accurate diagnosis of NEC, improving patient care.
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THEORETICAL FRAMEWORK Review of existing evidence Importance to the NHS and patients Congenital heart disease (CHD) is diagnosed in approximately 1 in 100 births.15 Significant CHD that required intervention in early childhood affected 3.6 per 1000 live births in England, 2004-2016.16 The unadjusted crude 30-day mortality rate amongst 9,586 paediatric cardiac operations undertaken between 2019-2022 was 2.1% but was highest in the youngest babies.7
The number one priority for the 'Research priorities in children and adults with congenital heart disease: a James Lind Alliance Priority Setting Partnership': how can damage to the gut during heart surgery in children with heart defects be minimised to reduce complications?17
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 0 Months 至 3 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants aged from birth up to 3 months old, of any gestational age who require admission to a specialist cardiac centre for treatment of major congenital heart disease.
- •Included patients are those who are judged as likely to require early cardiac surgery or interventional catheterisation, including babies who are treated with invasive medical therapies of respiratory support or intravenous vasoactive medications and their pathway will include a cardiac intervention of any type.
排除标准
- •Patients will be excluded if they are older than 3 months, do not have major heart disease and do have any gastrointestinal abnormality, including gastroschisis or imperforate anus.
- •Also, patients with neutropenia will be excluded since calprotectin is not activated when there is neutropenia.
结局指标
主要结局
Faecal calprotectin
时间窗: 2 years
Sensitivity and specificity of faecal calprotectin as a biomarker to detect true NEC cases in the study population based on gold standard evaluation
次要结局
未报告次要终点