Clinical trial NCT02289040: Acute Kidney Injury Following Paediatric Cardiac Surgery
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Kidney Injury
Keywords: Acute Kidney Injury
Microvesicles
microRNA
Paediatric cardiac surgery
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: University Hospitals, Leicester
name: Heart Link Children's Charity
name: British Heart Foundation
First posted: 2014-11-13
Enrollment: 24
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children undergoing cardiac surgery in a tertiary academic cardiac surgery unit

Brief summary: 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.

Detailed description: 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:

1. MV derived signals will differ in cyanotic patients, a patient group at significantly increased risk for AKI.
2. 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:

A.To establish the numbers of patients that are eligible for enrolment in the study, the number recruited to the study, and their clinical and demographic characteristics.

B.To determine the proportion of consented patients who develop AKI following cardiac surgery.

C.To measure perioperative changes in MV subgroups and MV associated miRNA, as well as platelet and monocyte activation, and the variance of these measures.

D.To establish protocol adherence, with respect to the adequacy and timing of the blood samples that are taken and the calculation of creatinine clearance perioperatively.

Eligibility criteria: Inclusion Criteria:

1. Patients undergoing congenital heart operations with cardio-pulmonary bypass.
2. Patients aged ≤ 17 years of age.
3. Patients with a body weight \> 2kg.

Exclusion Criteria:

1. Patients with pre-existing inflammatory state: sepsis undergoing treatment, acute kidney injury within 5 days or chronic inflammatory disease.
2. 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)
3. Patients where Extracorporeal Membrane Oxygenation (ECMO) support is required.
4. Patients likely to require ECMO postoperatively.

Primary outcomes:
measure: change from baseline in annexin V positive microvesicles
timeFrame: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
measure: change from baseline in microvesicles derived miRNA
timeFrame: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Secondary outcomes:
measure: Eligibility
timeFrame: pre-operatively
measure: Recruitment
timeFrame: preoperatively
measure: Protocol non-adherence
timeFrame: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
measure: Acute Kidney Injury
timeFrame: preoperatively, postoperatively every day until day 7
measure: Variation in Renal inflammation
timeFrame: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
measure: Incidence of Acute Lung Injury - Low Cardiac Output
timeFrame: preoperatively, postoperatively every day until day 7
measure: Incidence of Low Cardiac Output
timeFrame: preoperatively, postoperatively every day until day 7
measure: Variation in pro-coagulant potential of microvesicles
timeFrame: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
measure: Variations in sources of microvesicles
timeFrame: Pre-operatively, 6 - 12 hrs post-op and 24 hrs post-op
measure: Variations in systemic inflammatory cytokine response
timeFrame: Pre-operatively, 6 - 12 hrs post-op and 24 hrs post-op
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
state: Leicestershire
Study officials:
affiliation: University of Leicester
name: Gavin J Murphy, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sullo N, Mariani S, JnTala M, Kumar T, Wozniak MJ, Smallwood D, Pais P, Westrope C, Lotto A, Murphy GJ. An Observational Cohort Feasibility Study to Identify Microvesicle and Micro-RNA Biomarkers of Acute Kidney Injury Following Pediatric Cardiac Surgery. Pediatr Crit Care Med. 2018 Sep;19(9):816-830. doi: 10.1097/PCC.0000000000001604.