A Feasibility Study to Consider the Role of Microvesicles (MV) and MV Derived microRNA (miRNA) in Acute Kidney Injury (AKI) Following Paediatric Cardiac Surgery: p-MiVAKI Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- change from baseline in annexin V positive microvesicles
研究概览
简要总结
Acute kidney injury (AKI) complicates over 50% of cardiac surgical procedures in children where it increases morbidity and the use of healthcare resources. The pathogenesis of AKI is poorly understood, current diagnostic tests lack specificity and sensitivity, and there is no effective treatment. Improving outcomes in patients at risk of AKI has recently been defined as a National Health Service priority. The investigators are currently undertaking a program of work that is evaluating the role of plasma-derived microvesicles (MV) and MV associated microRNAs (miRNA) as diagnostic biomarkers or therapeutic targets in cardiac surgery patients at risk of developing AKI. Preliminary results indicate that these biomarkers may have clinical utility in adults. An important consideration is whether these biomarkers also have utility in children undergoing cardiac surgery. Measurement of MV at serial time points in children presents ethical challenges related to conducting clinical research in critically ill subjects. It also presents technical challenges related to the very small volumes of blood that may be sampled safely from babies and infants undergoing surgery. The aim of the study is to provide estimates of the perioperative variance of MV concentrations in 24 children undergoing cardiac surgery, as well as the frequency of AKI and other adverse events, protocol adherence and recruitment rates. This will assist with the design of a subsequent prospective observational study that will consider the role of MV/miRNA in children undergoing cardiac surgery.
详细描述
This is a prospective, single-centre observational feasibility study that will measure changes in MV signalling and their relationship to inflammatory responses after cardiac surgery in children.
The investigators primary hypothesis is that inflammatory renal injury following paediatric cardiac surgery is regulated by circulating MV and more specifically MV associated miRNA.
The investigators secondary hypotheses are:
- MV derived signals will differ in cyanotic patients, a patient group at significantly increased risk for AKI.
- MV subsets and/or MV derived miRNA may act as novel diagnostic biomarkers for AKI.
To assist with the design of a prospective observational study that will test these hypotheses the investigators propose to undertake a feasibility study in 24 children. The objectives of this feasibility study are:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Day 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients undergoing congenital heart operations with cardio-pulmonary bypass.
- •Patients aged ≤ 17 years of age.
- •Patients with a body weight > 2kg.
排除标准
- •Patients with pre-existing inflammatory state: sepsis undergoing treatment, acute kidney injury within 5 days or chronic inflammatory disease.
- •Emergency (operation before the beginning of the next working day after decision to operate) or salvage procedure (patients requiring cardiopulmonary resuscitation - external cardiac massage - en route to the operating theatre or prior to induction of anaesthesia. This does not include cardiopulmonary resuscitation following induction of anaesthesia)
- •Patients where Extracorporeal Membrane Oxygenation (ECMO) support is required.
- •Patients likely to require ECMO postoperatively.
结局指标
主要结局
change from baseline in annexin V positive microvesicles
时间窗: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Mean plasma concentration of Annexin V positive MV and the concentration variance in plasma from arterial blood samples collected prior to anaesthetic induction, and at 6-12 and 24 hours postoperatively.
change from baseline in microvesicles derived miRNA
时间窗: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Mean plasma concentration of MV derived miRNA and the concentration variance in plasma from arterial blood samples collected prior to anaesthetic induction, and at 6-12 and 24 hours postoperatively.
次要结局
- Eligibility(pre-operatively)
- Incidence of Acute Lung Injury - Low Cardiac Output(preoperatively, postoperatively every day until day 7)
- Incidence of Low Cardiac Output(preoperatively, postoperatively every day until day 7)
- Variations in sources of microvesicles(Pre-operatively, 6 - 12 hrs post-op and 24 hrs post-op)
- Recruitment(preoperatively)
- Protocol non-adherence(Pre-operatively, 6-12 hrs post-op and 24 hrs post-op)
- Variation in Renal inflammation(Pre-operatively, 6-12 hrs post-op and 24 hrs post-op)
- Variation in pro-coagulant potential of microvesicles(Pre-operatively, 6-12 hrs post-op and 24 hrs post-op)
- Acute Kidney Injury(preoperatively, postoperatively every day until day 7)
- Variations in systemic inflammatory cytokine response(Pre-operatively, 6 - 12 hrs post-op and 24 hrs post-op)