Acute Kidney InjuryMaRACASNCT02315183
An Observational Case Control Study to Identify the Role of MV and MV Derived Micro-RNA in Post CArdiac Surgery AKI
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 25% of cardiac surgical procedures where it increases mortality up to fourfold. The incidence of AKI is increasing, the pathogenesis 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 16 years and older
- Conditions the study is for
- Acute Kidney Injury
- What is being tested?
- This is an observational Study
- How many people
- 96 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2014to Mar 2016
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study will be carried out at a large tertiary academic cardiac surgery unit in the UK; the University Hospitals of Leicester NHS Trust. This unit performs over 1,200 major cardiac procedures per year, of which 300 are expected to develop acute kidney injury.
Who may be able to join
- Adult cardiac surgery patients (>16 years) undergoing coronary artery bypass grafting or valve surgery with moderately hypothermic CPB (32-34°C) blood cardioplegia.
- Identified as being at increased risk for AKI from a modified risk score.
Who cannot join
- Patients with pre-existing inflammatory state: sepsis undergoing treatment, acute kidney injury within 5 days, chronic inflammatory disease, congestive heart failure,
- Emergency or salvage procedure,
- Ejection fraction <30 %,
- Patient in a critical preoperative state (Kidney Disease: Improving Global Outcomes (KDIGO) Stage 3 AKI or requiring ionotropes, ventilation or intra-aortic balloon pump).
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Department of Cardiovascular Sciences.
Leicester, Leicestershire, LE3 9QP
About this study
Official title: An Observational Case Control Study to Identify the Role of MV and MV Derived Micro-RNA in Post CArdiac Surgery Acute Kidney Injury: The MaRACAS Study
Acute kidney injury (AKI) complicates over 25% of cardiac surgical procedures where it increases mortality up to fourfold. The incidence of AKI is increasing, the pathogenesis 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 an NHS priority. The primary aim of this study is to determine how plasma derived microvesicles (MV) or more specifically MV associated microRNAs (miRNA) regulate survival and signalling in post cardiac surgery AKI. The study involves a clinical and experimental research project that will combine laboratory analyses of circulating MV and miRNA from clinical studies. The study will specifically consider how MV and miRNA alter inflammatory signaling in kidneys after cardiac surgery, how these are modified by important clinical risk factors, and whether they may serve as early biomarkers of injury.
Read the detailed description
AKI is characterised by upregulation of competing pro-survival and pro- inflammatory/ apoptotic signaling pathways whereby processes associated with renal recovery; tubular epithelial phenotypic change and proliferation occur simultaneously with those associated with diminished GFR, vascular inflammation, tubular dysfunction and epithelial apoptosis. Protection from AKI can be achieved by altering the balance of these pathways; for example upregulation of the pivotal phosphatidylinositol 3-kinase - serine-threonine protein kinase B (PI3K-Akt) pro-survival pathway following the administration of erythropoietin or insulin like growth factor inhibits experimental AKI following renal ischaemia and reperfusion in rodents and swine. In our own work we have shown that post cardiopulmonary bypass (CPB) AKI in swine can be prevented by the administration of either a phosphodiesterase type 5 (PDE-5) inhibitor which promotes cell survival and endothelial homeostasis via augmentation of endogenous nitric oxide (NO) signalling, or by the inhibition of endothelin-1 (ET-1), an important pro-inflammatory mediator and promoter of oxidative stress in renal injury How these competing pathways are regulated in patients at risk of AKI is poorly understood however, and it is our belief that the identification of these processes will facilitate the development of new and effective prevention and treatment strategies for AKI and improved outcomes for patients
- Conditions
- Acute Kidney Injury
- Being tested
- This is an observational Study
- Keywords
- Post 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.
This is an observational StudyOther
Also called MaRACAS Study
THis study has no intervention
What is being measured
The primary outcome is the main question the study is designed to answer.
AKI defined according to the KDIGO criteria or by urine NGAL levels >150nmol/mg at 6 hours postoperatively.
Measured: 2 Years
Secondary outcomes (7)
Data on demographics, perioperative clinical characteristics and medications.
Measured: 2 Years
MV will be isolated from arterial blood samples collected prior to anaesthetic induction, at chest closure and at 6 and 24 hours postoperatively, and characterised using flow cytometry and NanoSight LM10 (Nanosight, London, UK).
Measured: 2 Years
Likely sources of MV will also be evaluated; Platelet and monocyte activation and aggregation will be determined by flow cytometry, endothelial activation will be determined by ELISA measurement of circulating ICAM and E-selectin in serum.
Measured: 2 Years
MV associated miRNA profiles will be determined using microarray in patients with AKI (n=6 diabetic, n=6 non diabetic) and a matched control group (n=6 diabetic, n=6 non diabetic) without AKI.
Measured: 2 Years
The systemic inflammatory response will be quantified by measurement of serum IL-8 and IL-6.
Measured: 2 Years
Renal inflammation will be determined by urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Liver type- Fatty Acid Binding Protein (L-FABP) measured at baseline, and then at 6 and 24 hours postoperatively.
Measured: 2 Years
MV and MV associated miRNA signaling will be evaluated ex vivo in a micro fluidics model.
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2014 (estimated)
- Study startJan 2014
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gavin Murphy, Prof, Principal investigator, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02315183
- Sponsor's protocol ID
- 0419
- Acronym
- MaRACAS
- Status last verified
- Dec 2014
- First submitted
- 9 Dec 2014
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Case Control Study to Identify the Role of MV and MV Derived Micro-RNA in Post CArdiac Surgery Acute Kidney Injury: The MaRACAS Study
- ClinicalTrials.gov ID
- NCT02315183
- Acronym / sponsor ID
- MaRACAS / 0419
- Conditions
- Acute Kidney Injury
- Keywords
- Post cardiac surgery
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 11 Dec 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 25% of cardiac surgical procedures where it increases mortality up to fourfold. The incidence of AKI is increasing, the pathogenesis 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 an NHS priority. The primary aim of this study is to determine how plasma derived microvesicles (MV) or more specifically MV associated microRNAs (miRNA) regulate survival and signalling in post cardiac surgery AKI. The study involves a clinical and experimental research project that will combine laboratory analyses of circulating MV and miRNA from clinical studies. The study will specifically consider how MV and miRNA alter inflammatory signaling in kidneys after cardiac surgery, how these are modified by important clinical risk factors, and whether they may serve as early biomarkers of injury.
Detailed description
AKI is characterised by upregulation of competing pro-survival and pro- inflammatory/ apoptotic signaling pathways whereby processes associated with renal recovery; tubular epithelial phenotypic change and proliferation occur simultaneously with those associated with diminished GFR, vascular inflammation, tubular dysfunction and epithelial apoptosis. Protection from AKI can be achieved by altering the balance of these pathways; for example upregulation of the pivotal phosphatidylinositol 3-kinase - serine-threonine protein kinase B (PI3K-Akt) pro-survival pathway following the administration of erythropoietin or insulin like growth factor inhibits experimental AKI following renal ischaemia and reperfusion in rodents and swine. In our own work we have shown that post cardiopulmonary bypass (CPB) AKI in swine can be prevented by the administration of either a phosphodiesterase type 5 (PDE-5) inhibitor which promotes cell survival and endothelial homeostasis via augmentation of endogenous nitric oxide (NO) signalling, or by the inhibition of endothelin-1 (ET-1), an important pro-inflammatory mediator and promoter of oxidative stress in renal injury How these competing pathways are regulated in patients at risk of AKI is poorly understood however, and it is our belief that the identification of these processes will facilitate the development of new and effective prevention and treatment strategies for AKI and improved outcomes for patients
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study will be carried out at a large tertiary academic cardiac surgery unit in the UK; the University Hospitals of Leicester NHS Trust. This unit performs over 1,200 major cardiac procedures per year, of which 300 are expected to develop acute kidney injury.
Key inclusion criteria (2 listed)
- Adult cardiac surgery patients (>16 years) undergoing coronary artery bypass grafting or valve surgery with moderately hypothermic CPB (32-34°C) blood cardioplegia.
- Identified as being at increased risk for AKI from a modified risk score.
Key exclusion criteria (5 listed)
- Patients with pre-existing inflammatory state: sepsis undergoing treatment, acute kidney injury within 5 days, chronic inflammatory disease, congestive heart failure,
- Emergency or salvage procedure,
- Ejection fraction <30 %,
- Patient in a critical preoperative state (Kidney Disease: Improving Global Outcomes (KDIGO) Stage 3 AKI or requiring ionotropes, ventilation or intra-aortic balloon pump).
- Pregnancy.
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 |
|---|---|---|
| This is an observational StudyAlso: MaRACAS StudyTHis study has no intervention | Other | – |
Primary outcome
AKI defined according to the KDIGO criteria or by urine NGAL levels >150nmol/mg at 6 hours postoperatively.
Time frame: 2 Years
7 secondary outcomes
Data on demographics, perioperative clinical characteristics and medications.
Time frame: 2 Years
MV will be isolated from arterial blood samples collected prior to anaesthetic induction, at chest closure and at 6 and 24 hours postoperatively, and characterised using flow cytometry and NanoSight LM10 (Nanosight, London, UK).
Time frame: 2 Years
Likely sources of MV will also be evaluated; Platelet and monocyte activation and aggregation will be determined by flow cytometry, endothelial activation will be determined by ELISA measurement of circulating ICAM and E-selectin in serum.
Time frame: 2 Years
MV associated miRNA profiles will be determined using microarray in patients with AKI (n=6 diabetic, n=6 non diabetic) and a matched control group (n=6 diabetic, n=6 non diabetic) without AKI.
Time frame: 2 Years
The systemic inflammatory response will be quantified by measurement of serum IL-8 and IL-6.
Time frame: 2 Years
Renal inflammation will be determined by urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Liver type- Fatty Acid Binding Protein (L-FABP) measured at baseline, and then at 6 and 24 hours postoperatively.
Time frame: 2 Years
MV and MV associated miRNA signaling will be evaluated ex vivo in a micro fluidics model.
Time frame: 2 Years
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 16 May 2024.
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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 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 2 inclusion and 5 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 16 May 2024. 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?
AKI defined according to the KDIGO criteria or by urine NGAL levels >150nmol/mg at 6 hours postoperatively. (time frame: 2 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 May 2024.