Back to resultsThe PRE-OP ENERGY Trial
Primary Purpose
Cardiac Valve Disease, Coronary Artery Disease, Organ Failure, Multiple
Status
Unknown status
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
High energy diet
Sponsored by
About this trial
This is an interventional treatment trial for Cardiac Valve Disease
Eligibility Criteria
Inclusion Criteria:
ALL of the following:
- Adult cardiac surgery patients (≥18 years) undergoing cardiac surgery (CABG, Valve, or CABG and Valve) with cardiopulmonary bypass.
- BMI<30
- Able, in the opinion of the investigator, and willing to give informed consent.
- Do not have diagnosed coeliac disease
- Able to understand English
Exclusion Criteria:
Any of the following:
- Urgent, emergency or salvage procedure
- Patients with end stage renal failure defined as an estimated Glomerular Filtration rate (eGFR) <15 mL/min/1.73 m2 calculated from the Modification of Diet in Renal Disease equation,1 or patients who are on long-term haemodialysis or have undergone renal transplantation.
- Patients with persistent or chronic atrial fibrillation.
- Patients with severe liver dysfunction; hepatitis, cirrhosis, jaundice.
- Women who are pregnant or who may become pregnant in the intraoperative period.
- Patients who are participating in another interventional clinical trial.
- Unable, in the opinion of the investigator, or unwilling to give informed consent.
- Have diagnosed coeliac disease
- Unable to understand English
Exclusion criteria for optional MRI research procedure:
- Permanent pacemaker or ICD
- Brain Aneurysm Clip
- Implanted neural stimulator
- Cochlear implant (specific implant must be checked that it is MR safe)
- Ocular foreign body (e.g. metal shavings) unless removed
- Other implanted medical devices: (e.g. Swan Ganz catheter)
- Insulin pump
- Retained metal shrapnel or bullet
- Claustrophobia
Sites / Locations
- University of LeicesterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Group A: Control
Group B: High energy diet
Arm Description
Standard Care
High energy diet for 8-12 weeks pre-surgery
Outcomes
Primary Outcome Measures
Change of Serum Creatinine level
Measurement of Serum Creatinine level and expressed as umol/L.
Change of Serum Troponin I level
Measurement of Serum Troponin level and expressed as ng/L.
Secondary Outcome Measures
Post-surgery organ injury: Sepsis-related Organ Failure
Sepsis-related Organ Failure Assessment (SOFA) Score. Range 0-3, 3 being the worse score
Post-surgery organ injury: Kidney Injury (Urinary Biomarkers) - NGAL (Neutrophil gelatinase associated lipocalcin)
Urine samples will be analysed for biomarkers of renal injury. Measurement of NGAL level will be expressed as μg/L.
Post-surgery organ injury: Kidney Injury (Urinary Biomarkers) - microRNA (Neutrophil gelatinase associated lipocalcin)
Urine samples will be analysed for biomarkers of renal injury. Measurement of microRNA in urine samples will be represented by the frequency (%) of identified microRNA.
Post-surgery organ injury: Kidney Injury
Absolute change from baseline for serum creatinine
Post-surgery organ injury: Kidney Injury
Serum creatinine and eGFR in all patients using the Modification of Diet in Renal Disease equation. The following is the IDMS-traceable MDRD Study equation (for creatinine methods calibrated to an IDMS reference method) GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American) The equation does not require weight or height variables because the results are reported normalized to 1.73 m2 body surface area, which is an accepted average adult surface area.
Post-surgery organ injury: Lung Injury using the Berlin ARDS Score
Using the Berlin ARDS score, the measurement of Arterial Alveolar oxygen ratio expressed in kPa/L.
Post-surgery organ injury: GI Tract injury (Biomarker) - AST (Aspartate Transaminase)
Measurement of AST levels in serum and expressed in IU/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Post-surgery organ injury: GI Tract injury (Biomarker) - ALT (Alanine Transaminase)
Measurement of ALT levels in serum and expressed in IU/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Post-surgery organ injury: GI Tract injury (Biomarker) - Bilirubin
Measurement of Bilirubin levels in serum and expressed in μmol/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Post-surgery organ injury: GI Tract injury (Biomarker) - Alkaline Phosphatase
Measurement of Alkaline Phosphatase levels in serum and expressed in IU/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Post-surgery organ injury: GI Tract injury (Biomarker) - Serum Amylase
Measurement of Amylase levels in serum and expressed in IU/L. Acute pancreatitis will be defined as a serum amylase concentration >1000 ng/ml.
Assessment of resource use: Extubation
Time until extubation
Assessment of resource use: Intensive Care Unit
Length of stay in Intensive Care Unit. Number of hours between admission and discharge from the High Dependency Unit (HDU)
Assessment of resource use: Hospital Stay
Length of stay in hospital. Number of days between admission and discharge from the hospital
Clinical events: Sepsis
Sepsis will be defined as suspected or documented infection and an acute change in total SOFA score ≥2 points consequent to the infection. For the purposes of the trial suspected or documented infection will be defined as the commencement of intravenous antibiotics. The rise in SOFA score will be assessed within 72 hours of the commencement of antibiotics. Range of SOFA is 0 to 3, 3 being the worse. For the purposes of the study suspected or documented infection will be defined as the commencement of intravenous antibiotics. The rise in SOFA score will be assessed within 72 hours of the commencement of antibiotics.
Clinical events: Peak lactate
Peak lactate within 24 hours of surgery and time to resolution of hyperlactataemia (arterial serum lactate >2.5 mmol/L) post peak.
Clinical events: Acute Lung Injury
Measurement of PaO2/FiO2 ratio and expressed in kPa/L.
Clinical events: Low cardiac output
Low cardiac output, defined as new intra-or postoperative intra-aortic balloon pump insertion or a cardiac index of <2.2 L/min/ m2 refractory to appropriate intravascular volume expansion after correction or attempted correction of any dysrhythmias, or the administration of the inotropes Dobutamine, Enoximone, Milrinone or Levosimendan.
Clinical events: Stroke
Stroke; diagnosed by brain imaging (CT or MRI), in association with new onset focal or generalized neurological deficit (defined as deficit in motor, sensory or co-ordination functions)
Clinical events: Acute Liver Injury - AST (Aspartate Transaminase)
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Clinical events: Acute Liver Injury - ALT (Alanine Transaminase)
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Clinical events: Acute Liver Injury - Bilirubin
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Clinical events: Acute Liver Injury - Alkaline Phosphatase
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Clinical events: Acute Liver Injury - Serum Amylase
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Clinical events: Acute Intestinal Injury
Acute intestinal injury will be defined a radiological, operative or post-mortem evidence of gut ischaemia.
Clinical events: Rate of mortality
Rate of mortality at 30-days and 1 year from the date of surgery
Clinical events: A composite endpoint Organ Injury, Mortality and Sepsis
As above for description of organ injury, mortality and sepsis
Bleeding and Transfusion
The total number of units of red cells and other blood components transfused during the operative period and post-operative hospital stay will be recorded
Mechanism study: Mitochondrial function of microvessels from tissue biopsies
50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.
Mechanism study: microRNA isolation of microvessels from tissue biopsies
The findings will be represented by the frequency (%) of identified microRNA. 50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies.
Mechanism study: Chromatin Immunoprecipitation (ChIP) of microvessels from tissue biopsies
To identify protein binding sites that may help identify functional elements in the genome. Findings will be represented by the number (n) of binding sites. 50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies.
Mechanism study: Mitochondrial function measured in right atrium myocardium tissue biopsies
50-100 mg myocardial biopsies will be obtained from the right atrium at surgery. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.
Mechanism study: microRNA isolation in right atrium myocardium tissue biopsies
50-100 mg myocardial biopsies will be obtained from the right atrium at surgery. The findings will be represented by the frequency (%) of identified microRNA.
Mechanism study: Chromatin Immunoprecipitation (ChIP) in right atrium myocardium tissue biopsies
50-100 mg myocardial biopsies will be obtained from the right atrium at surgery. To identify protein binding sites that may help identify functional elements in the genome. Findings will be represented by the number (n) of binding sites.
Mechanism study: Mitochondrial function measured in adipose tissue biopsies
Adipose tissue collected from epicardial fat at time of surgery. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.
Mechanism study: microRNA isolation in adipose tissue biopsies
Adipose tissue collected from epicardial fat at time of surgery. The findings will be represented by the frequency (%) of identified microRNA.
Mechanism study: Chromatin Immunoprecipitation (ChIP) in adipose tissue biopsies
Adipose tissue collected from epicardial fat at time of surgery. To identify protein binding sites that may help identify functional elements in the genome. Findings will be represented by the number (n) of binding sites.
Mechanism study: Measurement of microvesicles in urine samples
Identification of microvesicles. The findings will be represented by the frequency (%) of each identified microvesicle.
Mechanism study: Measurement of microRNA in urine samples
The findings will be represented by the frequency (%) of identified microRNA.
Mechanism study: Measurement of histone acetylation in urine samples
The findings will be reported as acetylated H3 (ug/mg) over time (hours)
Mechanism study: Measurement of gene expression in urine samples
Whole genome sequencing will be achieved through ATAC sequencing. The identified genes will be characterised by average expression count over ATAC.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04015973
Brief Title
The PRE-OP ENERGY Trial
Official Title
A Randomised Controlled Trial of a Pre-operative High Energy Diet for the Prevention of Organ Injury in Cardiac Surgery: The PRE-OP ENERGY Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
May 7, 2019 (Actual)
Primary Completion Date
April 2022 (Anticipated)
Study Completion Date
July 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Leicester
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The PRE-OP ENERGY Trial proposes to test the overarching hypothesis that a pre-surgery high energy diet will protect patients against organ damage during cardiac surgery with cardiopulmonary bypass.
Detailed Description
PRE-OP ENERGY is a single centre, unblinded, parallel group, randomised controlled trial of a pre-operative high energy diet, versus a control group receiving standard care.
The trial will test a number of specific hypotheses:
A pre-surgery high energy diet will protect against post-cardiac surgery organ failure by altering the pre-surgery cardiometabolic state, a process referred to as 'metabolic preconditioning'.
The effects of the trial intervention will not be attributable to changes in frailty, activity or baseline organ dysfunction.
The trial intervention will not result in long-term adverse changes in cardiometabolic status.
Metabolic preconditioning will confer protection against post-cardiac surgery kidney injury by increasing the expression of genes that promote renal tubular homeostasis.
Metabolic preconditioning will confer protection against post-cardiac surgery myocardial injury by increasing the expression of genes that promote myocardial mitochondrial homeostasis via effects on chromatin histone deacetylation.
Metabolic preconditioning will confer protection against post-cardiac surgery endothelial dysfunction by increasing the expression of genes that promote endothelial homeostasis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Valve Disease, Coronary Artery Disease, Organ Failure, Multiple
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Unblinded randomised controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
116 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A: Control
Arm Type
No Intervention
Arm Description
Standard Care
Arm Title
Group B: High energy diet
Arm Type
Experimental
Arm Description
High energy diet for 8-12 weeks pre-surgery
Intervention Type
Dietary Supplement
Intervention Name(s)
High energy diet
Intervention Description
An overfeeding regime of 135% required energy intake per day, set from baseline energy requirements consisting of high (saturated) fat snacks, added to the usual diet, supervised by a dietitian.
Primary Outcome Measure Information:
Title
Change of Serum Creatinine level
Description
Measurement of Serum Creatinine level and expressed as umol/L.
Time Frame
Baseline, 0-6, 6-12, 24, 48, 72, and up to 96 hours post-operatively
Title
Change of Serum Troponin I level
Description
Measurement of Serum Troponin level and expressed as ng/L.
Time Frame
Baseline, 0-6, 6-12, 24, 48 and 72 hours post-operatively
Secondary Outcome Measure Information:
Title
Post-surgery organ injury: Sepsis-related Organ Failure
Description
Sepsis-related Organ Failure Assessment (SOFA) Score. Range 0-3, 3 being the worse score
Time Frame
Baseline, pre-operatively, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively
Title
Post-surgery organ injury: Kidney Injury (Urinary Biomarkers) - NGAL (Neutrophil gelatinase associated lipocalcin)
Description
Urine samples will be analysed for biomarkers of renal injury. Measurement of NGAL level will be expressed as μg/L.
Time Frame
Baseline, 1 day pre-op, 6-12, 24 and 48 hours post-operatively
Title
Post-surgery organ injury: Kidney Injury (Urinary Biomarkers) - microRNA (Neutrophil gelatinase associated lipocalcin)
Description
Urine samples will be analysed for biomarkers of renal injury. Measurement of microRNA in urine samples will be represented by the frequency (%) of identified microRNA.
Time Frame
Baseline, 1 day pre-op, 6-12, 24 and 48 hours post-operatively
Title
Post-surgery organ injury: Kidney Injury
Description
Absolute change from baseline for serum creatinine
Time Frame
Daily for 5 days from Baseline
Title
Post-surgery organ injury: Kidney Injury
Description
Serum creatinine and eGFR in all patients using the Modification of Diet in Renal Disease equation. The following is the IDMS-traceable MDRD Study equation (for creatinine methods calibrated to an IDMS reference method) GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American) The equation does not require weight or height variables because the results are reported normalized to 1.73 m2 body surface area, which is an accepted average adult surface area.
Time Frame
At 6 weeks and then 3 months post-surgery
Title
Post-surgery organ injury: Lung Injury using the Berlin ARDS Score
Description
Using the Berlin ARDS score, the measurement of Arterial Alveolar oxygen ratio expressed in kPa/L.
Time Frame
Baseline, immediately pre-surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively
Title
Post-surgery organ injury: GI Tract injury (Biomarker) - AST (Aspartate Transaminase)
Description
Measurement of AST levels in serum and expressed in IU/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Time Frame
Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
Title
Post-surgery organ injury: GI Tract injury (Biomarker) - ALT (Alanine Transaminase)
Description
Measurement of ALT levels in serum and expressed in IU/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Time Frame
Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
Title
Post-surgery organ injury: GI Tract injury (Biomarker) - Bilirubin
Description
Measurement of Bilirubin levels in serum and expressed in μmol/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Time Frame
Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
Title
Post-surgery organ injury: GI Tract injury (Biomarker) - Alkaline Phosphatase
Description
Measurement of Alkaline Phosphatase levels in serum and expressed in IU/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Time Frame
Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
Title
Post-surgery organ injury: GI Tract injury (Biomarker) - Serum Amylase
Description
Measurement of Amylase levels in serum and expressed in IU/L. Acute pancreatitis will be defined as a serum amylase concentration >1000 ng/ml.
Time Frame
Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
Title
Assessment of resource use: Extubation
Description
Time until extubation
Time Frame
Time (hours) measured from the start of surgery to extubation (up to 30 days)
Title
Assessment of resource use: Intensive Care Unit
Description
Length of stay in Intensive Care Unit. Number of hours between admission and discharge from the High Dependency Unit (HDU)
Time Frame
Time (hours) measured from the start of surgery to discharge from ICU (up to 30 days)
Title
Assessment of resource use: Hospital Stay
Description
Length of stay in hospital. Number of days between admission and discharge from the hospital
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Sepsis
Description
Sepsis will be defined as suspected or documented infection and an acute change in total SOFA score ≥2 points consequent to the infection. For the purposes of the trial suspected or documented infection will be defined as the commencement of intravenous antibiotics. The rise in SOFA score will be assessed within 72 hours of the commencement of antibiotics. Range of SOFA is 0 to 3, 3 being the worse. For the purposes of the study suspected or documented infection will be defined as the commencement of intravenous antibiotics. The rise in SOFA score will be assessed within 72 hours of the commencement of antibiotics.
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Peak lactate
Description
Peak lactate within 24 hours of surgery and time to resolution of hyperlactataemia (arterial serum lactate >2.5 mmol/L) post peak.
Time Frame
Within 24 hours of surgery
Title
Clinical events: Acute Lung Injury
Description
Measurement of PaO2/FiO2 ratio and expressed in kPa/L.
Time Frame
Baseline, immediately pre-surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively
Title
Clinical events: Low cardiac output
Description
Low cardiac output, defined as new intra-or postoperative intra-aortic balloon pump insertion or a cardiac index of <2.2 L/min/ m2 refractory to appropriate intravascular volume expansion after correction or attempted correction of any dysrhythmias, or the administration of the inotropes Dobutamine, Enoximone, Milrinone or Levosimendan.
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Stroke
Description
Stroke; diagnosed by brain imaging (CT or MRI), in association with new onset focal or generalized neurological deficit (defined as deficit in motor, sensory or co-ordination functions)
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Acute Liver Injury - AST (Aspartate Transaminase)
Description
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Acute Liver Injury - ALT (Alanine Transaminase)
Description
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Acute Liver Injury - Bilirubin
Description
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Acute Liver Injury - Alkaline Phosphatase
Description
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Acute Liver Injury - Serum Amylase
Description
Acute liver injury will be defined as an acute derangement of liver enzymes three times the upper limit of normal, or a serum amylase concentration >1000 ng/m.
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Acute Intestinal Injury
Description
Acute intestinal injury will be defined a radiological, operative or post-mortem evidence of gut ischaemia.
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Clinical events: Rate of mortality
Description
Rate of mortality at 30-days and 1 year from the date of surgery
Time Frame
Within 30-days from surgery and at 1 year from surgery
Title
Clinical events: A composite endpoint Organ Injury, Mortality and Sepsis
Description
As above for description of organ injury, mortality and sepsis
Time Frame
Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Title
Bleeding and Transfusion
Description
The total number of units of red cells and other blood components transfused during the operative period and post-operative hospital stay will be recorded
Time Frame
Blood loss at 6 hours post-operatively
Title
Mechanism study: Mitochondrial function of microvessels from tissue biopsies
Description
50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.
Time Frame
At time of surgery
Title
Mechanism study: microRNA isolation of microvessels from tissue biopsies
Description
The findings will be represented by the frequency (%) of identified microRNA. 50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies.
Time Frame
At time of surgery
Title
Mechanism study: Chromatin Immunoprecipitation (ChIP) of microvessels from tissue biopsies
Description
To identify protein binding sites that may help identify functional elements in the genome. Findings will be represented by the number (n) of binding sites. 50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies.
Time Frame
At time of surgery
Title
Mechanism study: Mitochondrial function measured in right atrium myocardium tissue biopsies
Description
50-100 mg myocardial biopsies will be obtained from the right atrium at surgery. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.
Time Frame
At time of surgery
Title
Mechanism study: microRNA isolation in right atrium myocardium tissue biopsies
Description
50-100 mg myocardial biopsies will be obtained from the right atrium at surgery. The findings will be represented by the frequency (%) of identified microRNA.
Time Frame
At time of surgery
Title
Mechanism study: Chromatin Immunoprecipitation (ChIP) in right atrium myocardium tissue biopsies
Description
50-100 mg myocardial biopsies will be obtained from the right atrium at surgery. To identify protein binding sites that may help identify functional elements in the genome. Findings will be represented by the number (n) of binding sites.
Time Frame
At time of surgery
Title
Mechanism study: Mitochondrial function measured in adipose tissue biopsies
Description
Adipose tissue collected from epicardial fat at time of surgery. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.
Time Frame
At time of surgery
Title
Mechanism study: microRNA isolation in adipose tissue biopsies
Description
Adipose tissue collected from epicardial fat at time of surgery. The findings will be represented by the frequency (%) of identified microRNA.
Time Frame
At time of surgery
Title
Mechanism study: Chromatin Immunoprecipitation (ChIP) in adipose tissue biopsies
Description
Adipose tissue collected from epicardial fat at time of surgery. To identify protein binding sites that may help identify functional elements in the genome. Findings will be represented by the number (n) of binding sites.
Time Frame
At time of surgery
Title
Mechanism study: Measurement of microvesicles in urine samples
Description
Identification of microvesicles. The findings will be represented by the frequency (%) of each identified microvesicle.
Time Frame
Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively.
Title
Mechanism study: Measurement of microRNA in urine samples
Description
The findings will be represented by the frequency (%) of identified microRNA.
Time Frame
Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively.
Title
Mechanism study: Measurement of histone acetylation in urine samples
Description
The findings will be reported as acetylated H3 (ug/mg) over time (hours)
Time Frame
Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively.
Title
Mechanism study: Measurement of gene expression in urine samples
Description
Whole genome sequencing will be achieved through ATAC sequencing. The identified genes will be characterised by average expression count over ATAC.
Time Frame
Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively.
Other Pre-specified Outcome Measures:
Title
Body Composition: Bone Density Scan (DEXA)
Description
Assessments of muscle mass/sarcopenia (Appendicular lean mass taken from the DEXA scan)
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Imaging Assessment of Cardiometabolic Status: Trans-Oesophageal Echo
Description
Diastolic and systolic left ventricular function will be evaluated using intra-operative trans-oesophageal echo in all patients, as per standard care.
Time Frame
At time of surgery
Title
Imaging Assessment (optional): Cardiac Magnetic Resonance Imaging - Cardiac Function
Description
Assessment of cardiac function, by assessing ventricular function. This will be expressed as ejection fraction (%). Intravenous contrast will be administered via an indwelling venous catheter.
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Imaging Assessment (optional): Cardiac Magnetic Resonance Imaging - Cardiac adiposity content
Description
Assessment of cardiac adiposity content. A percentage of adipose tissue over total body mass will be calculated. Intravenous contrast will be administered via an indwelling venous catheter.
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Imaging Assessment (optional): Cardiac Magnetic Resonance Imaging - Visceral adiposity content
Description
Assessment of visceral adiposity content. A percentage of adipose tissue over total body mass will be calculated. Intravenous contrast will be administered via an indwelling venous catheter.
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Fitness, Frailty and Muscle Strength: Six Minute Walk Test
Description
Fitness will be assessed using the 6-minute walk test (6MWT) which is a standardized test that provides a valid assessment of functional performance. It provides a global assessment of exercise capacity and may better reflect daily activity than more traditional laboratory tests.
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Fitness, Frailty and Muscle Strength: Hand Grip Test
Description
Hand grip strength will be measured quantitatively by using a dynamometer. The result provides an objective index of general upper body strength and combined with appendicular lean mass (taken from the DEXA scan) could be used to define sarcopenia.
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Fitness, Frailty and Muscle Strength: PRISMA-7 Questionnaire
Description
Frailty assessment will be by use of the PRISMA-7 Questionnaire. The questions asked are: 1. Are you older than 85 years? 2. Are you male? 3. In general, do you have any health problems that require you to limit your activities? 4. Do you need someone to help you on a regular basis? 5. In general, do you have any health problems that require you to stay at home? 6. If you need help, can you count on someone close to you? 7. Do you regularly use a stick, walker or wheelchair to move about? The participant is asked to answer Yes or No to all 7 questions. SCORING: If the respondent had 3 or more "yes" answers, this indicates an increased risk of frailty and the need for further clinical review.
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Activity Levels and Sleep: Accelerometer Assessments
Description
Activity levels and sleep are measured by the use of seven day accelerometer assessments
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Comorbidity and Inflammation - CRP (C-Reactive-Protein) assay (Abcam)
Description
Pre-existing inflammation, renal impairment and heart failure will be assessed using highly sensitive CRP assay, NT-proBNP (both Abcam), and estimated Glomerular Filtration Rate (from serum creatinine). The acceptable range for CRP values using the abcam kit is 34.29 - 25,000 pg/mL. For values above 25ng/mL, the samples will be diluted and re-assayed. Samples < 34.29 pg/mL will be re-assayed at higher concentration when possible; otherwise the concentrations will be accepted if higher than assay detection limit (2 pg/L). For samples <2pg/mL a no-expression value will be assigned.
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Comorbidity and Inflammation - NT-proBNP (Abcam)
Description
Pre-existing inflammation, renal impairment and heart failure will be assessed using highly sensitive CRP assay, NT-proBNP (both Abcam), and estimated Glomerular Filtration Rate (from serum creatinine). The acceptable range for NT-proBNP values using the abcam kit is 0.14 - 100 ng/mL. For values above 100ng/mL, the samples will be diluted and re-assayed. Samples < 0.14 ng/mL will be re-assayed at higher concentration when possible; otherwise a no-expression value will be assigned.
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Comorbidity and Inflammation - estimated Glomerular Filtration Rate
Description
Pre-existing inflammation, renal impairment and heart failure will be assessed using highly sensitive CRP assay, NT-proBNP (both Abcam), and estimated Glomerular Filtration Rate (from serum creatinine). Formula for GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American) The equation does not require weight or height variables because the results are reported normalized to 1.73 m2 body surface area, which is an accepted average adult surface area.
Time Frame
Baseline, pre-assessment and 3 months post-surgery
Title
Endothelial function: Blood samples
Description
Markers of endothelial activation will be measured in blood samples using flow cytometry.
Time Frame
Baseline, 6-12 and 48 hours post-surgery
Title
Endothelial function: Reactive Hyperaemia Peripheral Arterial Tonometry (RH-PAT)
Description
Regional endothelial dysfunction will be measured as the reactive hyperaemia peripheral arterial tonometry (RH-PAT) index using the Endo-PAT 2000 (Itamar Medical Ltd., Caesarea, Israel)
Time Frame
1 day before surgery and 24 hours post-surgery
Title
Endothelial function: Global endothelial dysfunction
Description
Global endothelial dysfunction will also be measured indirectly as the measured time to resolution of oxygen debt defined as the period of time from the end of surgery until the measured serum arterial lactate level falls below 2.5 mmol/L.
Time Frame
End of surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively (until the timepoint serum arterial lactate falls below 2.5 mmol/L)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
ALL of the following:
Adult cardiac surgery patients (≥18 years) undergoing cardiac surgery (CABG, Valve, or CABG and Valve) with cardiopulmonary bypass.
BMI<30
Able, in the opinion of the investigator, and willing to give informed consent.
Do not have diagnosed coeliac disease
Able to understand English
Exclusion Criteria:
Any of the following:
Urgent, emergency or salvage procedure
Patients with end stage renal failure defined as an estimated Glomerular Filtration rate (eGFR) <15 mL/min/1.73 m2 calculated from the Modification of Diet in Renal Disease equation,1 or patients who are on long-term haemodialysis or have undergone renal transplantation.
Patients with persistent or chronic atrial fibrillation.
Patients with severe liver dysfunction; hepatitis, cirrhosis, jaundice.
Women who are pregnant or who may become pregnant in the intraoperative period.
Patients who are participating in another interventional clinical trial.
Unable, in the opinion of the investigator, or unwilling to give informed consent.
Have diagnosed coeliac disease
Unable to understand English
Exclusion criteria for optional MRI research procedure:
Permanent pacemaker or ICD
Brain Aneurysm Clip
Implanted neural stimulator
Cochlear implant (specific implant must be checked that it is MR safe)
Ocular foreign body (e.g. metal shavings) unless removed
Other implanted medical devices: (e.g. Swan Ganz catheter)
Insulin pump
Retained metal shrapnel or bullet
Claustrophobia
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mustafa Zakkar, PhD
Phone
0116258
Ext
3019
Email
mz207@le.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Hardeep Aujla
Phone
0116250
Ext
2650
Email
ha200@le.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gavin J Murphy, MD
Organizational Affiliation
BHF Professor of Cardiac Surgery, University of Leicester
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mustafa Zakkar, PhD
Organizational Affiliation
Associate Professor, University of Leicester
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Leicester
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE3 9QP
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The PRE-OP ENERGY Trial
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