Acute Kidney Injuryp-MiVAKINCT02289040
Acute Kidney Injury Following Paediatric Cardiac Surgery
An observational study of Acute Kidney Injury, run by University of Leicester at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 17 years
- Conditions the study is for
- Acute Kidney Injury
- What is being tested?
- cardiac surgery
- Type of treatment
- Surgery or procedure
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2014to May 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: Children undergoing cardiac surgery in a tertiary academic cardiac surgery unit
Who may be able to join
- Patients undergoing congenital heart operations with cardio-pulmonary bypass.
- Patients aged ≤ 17 years of age.
- Patients with a body weight > 2kg.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Glenfield Hospital
Leicester, Leicestershire, LE3 9QP
About this study
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
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.
Read the 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:
- 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:
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.
- Conditions
- Acute Kidney Injury
- Being tested
- cardiac surgery
- Keywords
- Acute Kidney Injury, Microvesicles, microRNA, Paediatric cardiac surgery
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cardiac surgeryProcedure or surgery
cardiac surgery with extracorporeal circulation for congenital heart disease
| Study group | Role | What they receive |
|---|---|---|
| Children undergoing cardiac surgery | Paediatric patients (<17 years with a body weight >2000g) undergoing cardiac surgery for congenital heart disease with extracorporeal circulation Receives: Procedure: cardiac surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
change from baseline in annexin V positive microvesicles
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.
Measured: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
change from baseline in microvesicles derived miRNA
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.
Measured: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Secondary outcomes (10)
Eligibility
Since this is a feasibility study, the investigators will evaluate the rate of patients who are eligible among the whole population of screened patients
Measured: pre-operatively
Recruitment
Since this is a feasibility study, the investigators will evaluate the rate of patients who will be recruited among the whole population of approached patients
Measured: preoperatively
Protocol non-adherence
Since this is a feasibility study, the investigators will evaluate protocol non-adherence defined as the failure to obtain the specified blood volume or urine sample required for analysis at the required time.
Measured: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Acute Kidney Injury
Acute kidney injury defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Measured: preoperatively, postoperatively every day until day 7
Variation in Renal inflammation
Variation in Renal inflammation will be determined by variation in values of urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Liver type- Fatty Acid Binding Protein (L-FABP) and urinary nitric oxide bioavailability .
Measured: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Incidence of Acute Lung Injury - Low Cardiac Output
Acute Lung Injury (PaO2/FiO2<300mmHg)
Measured: preoperatively, postoperatively every day until day 7
Incidence of Low Cardiac Output
Low Cardiac Output (the use of two or more inotropes)
Measured: preoperatively, postoperatively every day until day 7
Variation in pro-coagulant potential of microvesicles
This is a measure of MV tissue factor expression and indicates the likely pro-inflammatory effect of the MV.
Measured: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Variations in sources of microvesicles
Sources of MV: platelet, endothelial and monocyte activation will be determined by flow cytometry.
Measured: Pre-operatively, 6 - 12 hrs post-op and 24 hrs post-op
Variations in systemic inflammatory cytokine response
The systemic inflammatory cytokine response will be quantified by measurement of serum interleukin-8, interleukin-6, tumor necrosis factor -α, monocyte chemotactic protein -1, monocyte chemotactic protein -3, intercellular adhesion molecule, E-selectin.
Measured: Pre-operatively, 6 - 12 hrs post-op and 24 hrs post-op
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2014 (estimated)
- Study startOct 2014
- Primary completionMay 2017
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospitals, Leicester, Heart Link Children's Charity, British Heart Foundation
- Responsible party
- Sponsor
- Investigators
- Gavin J Murphy, Prof, Principal investigator, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02289040
- Sponsor's protocol ID
- 0463
- Other IDs
- 14/EM/1136
- Acronym
- p-MiVAKI
- Status last verified
- May 2017
- First submitted
- 2 Sep 2014
- Last updated
- 30 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 29912813
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02289040
- Acronym / sponsor ID
- p-MiVAKI / 0463
- Conditions
- Acute Kidney Injury
- Keywords
- Acute Kidney Injury, Microvesicles, microRNA, Paediatric cardiac surgery
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Collaborators
- University Hospitals, Leicester, Heart Link Children's Charity, British Heart Foundation
- Study start
- Oct 2014 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 13 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children undergoing cardiac surgery | – | Procedure: cardiac surgeryPaediatric patients (<17 years with a body weight >2000g) undergoing cardiac surgery for congenital heart disease with extracorporeal circulation |
Who may qualify
- Ages
- 1 day to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Children undergoing cardiac surgery in a tertiary academic cardiac surgery unit
Key inclusion criteria (3 listed)
- Patients undergoing congenital heart operations with cardio-pulmonary bypass.
- Patients aged ≤ 17 years of age.
- Patients with a body weight > 2kg.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cardiac surgerycardiac surgery with extracorporeal circulation for congenital heart disease | Procedure or surgery | Children undergoing cardiac surgery |
Primary outcome
change from baseline in annexin V positive microvesicles
Time frame: 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
Time frame: 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.
10 secondary outcomes
Eligibility
Time frame: pre-operatively
Recruitment
Time frame: preoperatively
Protocol non-adherence
Time frame: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Acute Kidney Injury
Time frame: preoperatively, postoperatively every day until day 7
Variation in Renal inflammation
Time frame: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Incidence of Acute Lung Injury - Low Cardiac Output
Time frame: preoperatively, postoperatively every day until day 7
Incidence of Low Cardiac Output
Time frame: preoperatively, postoperatively every day until day 7
Variation in pro-coagulant potential of microvesicles
Time frame: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op
Variations in sources of microvesicles
Time frame: Pre-operatively, 6 - 12 hrs post-op and 24 hrs post-op
Variations in systemic inflammatory cytokine response
Time frame: Pre-operatively, 6 - 12 hrs post-op and 24 hrs post-op
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2020.
- Derived from this study: PubMed 29912813Sullo 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gavin J Murphy, Prof principal investigator
University of Leicester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Kidney Injury, run by University of Leicester at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change from baseline in annexin V positive microvesicles (time frame: Pre-operatively, 6-12 hrs post-op and 24 hrs post-op). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02289040, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2020.