The PRE-OP ENERGY Trial
- Conditions
- Coronary Artery DiseaseOrgan Failure, MultipleCardiac Valve Disease
- Interventions
- Dietary Supplement: High energy diet
- Registration Number
- NCT04015973
- Lead Sponsor
- University of Leicester
- 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:
1. 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'.
2. The effects of the trial intervention will not be attributable to changes in frailty, activity or baseline organ dysfunction.
3. The trial intervention will not result in long-term adverse changes in cardiometabolic status.
4. Metabolic preconditioning will confer protection against post-cardiac surgery kidney injury by increasing the expression of genes that promote renal tubular homeostasis.
5. 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.
6. Metabolic preconditioning will confer protection against post-cardiac surgery endothelial dysfunction by increasing the expression of genes that promote endothelial homeostasis.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 116
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B: High energy diet High energy diet High energy diet for 8-12 weeks pre-surgery
- Primary Outcome Measures
Name Time Method Change of Serum Troponin I level Baseline, 0-6, 6-12, 24, 48 and 72 hours post-operatively Measurement of Serum Troponin level and expressed as ng/L.
Change of Serum Creatinine level Baseline, 0-6, 6-12, 24, 48, 72, and up to 96 hours post-operatively Measurement of Serum Creatinine level and expressed as umol/L.
- Secondary Outcome Measures
Name Time Method Post-surgery organ injury: GI Tract injury (Biomarker) - Bilirubin Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively. 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: Sepsis-related Organ Failure Baseline, pre-operatively, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively 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) Baseline, 1 day pre-op, 6-12, 24 and 48 hours post-operatively Urine samples will be analysed for biomarkers of renal injury. Measurement of NGAL level will be expressed as μg/L.
Post-surgery organ injury: GI Tract injury (Biomarker) - Serum Amylase Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively. Measurement of Amylase levels in serum and expressed in IU/L. Acute pancreatitis will be defined as a serum amylase concentration \>1000 ng/ml.
Clinical events: Stroke Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) 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: Rate of mortality Within 30-days from surgery and at 1 year from surgery Rate of mortality at 30-days and 1 year from the date of surgery
Bleeding and Transfusion Blood loss at 6 hours post-operatively 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: Chromatin Immunoprecipitation (ChIP) of microvessels from tissue biopsies 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. 50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies.
Mechanism study: Mitochondrial function measured in right atrium myocardium tissue biopsies At time of surgery 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.
Post-surgery organ injury: Lung Injury using the Berlin ARDS Score Baseline, immediately pre-surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively Using the Berlin ARDS score, the measurement of Arterial Alveolar oxygen ratio expressed in kPa/L.
Post-surgery organ injury: GI Tract injury (Biomarker) - Alkaline Phosphatase Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively. 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.
Assessment of resource use: Intensive Care Unit Time (hours) measured from the start of surgery to discharge from ICU (up to 30 days) 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 Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) Length of stay in hospital. Number of days between admission and discharge from the hospital
Clinical events: Acute Liver Injury - ALT (Alanine Transaminase) Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) 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 Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) 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.
Mechanism study: Mitochondrial function of microvessels from tissue biopsies At time of surgery 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 At time of surgery 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) in right atrium myocardium tissue biopsies At time of surgery 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: Chromatin Immunoprecipitation (ChIP) in adipose tissue biopsies At time of surgery 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.
Post-surgery organ injury: GI Tract injury (Biomarker) - ALT (Alanine Transaminase) Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively. 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.
Clinical events: Low cardiac output Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) 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.
Mechanism study: Measurement of microRNA in urine samples Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively. The findings will be represented by the frequency (%) of identified microRNA.
Post-surgery organ injury: Kidney Injury (Urinary Biomarkers) - microRNA (Neutrophil gelatinase associated lipocalcin) Baseline, 1 day pre-op, 6-12, 24 and 48 hours post-operatively 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 At 6 weeks and then 3 months post-surgery 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: GI Tract injury (Biomarker) - AST (Aspartate Transaminase) Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively. 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.
Clinical events: Sepsis Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) 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 Within 24 hours of surgery 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 Liver Injury - Bilirubin Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) 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.
Mechanism study: microRNA isolation in right atrium myocardium tissue biopsies At time of surgery 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.
Assessment of resource use: Extubation Time (hours) measured from the start of surgery to extubation (up to 30 days) Time until extubation
Clinical events: Acute Lung Injury Baseline, immediately pre-surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively Measurement of PaO2/FiO2 ratio and expressed in kPa/L.
Clinical events: Acute Liver Injury - AST (Aspartate Transaminase) Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) 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 Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) 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 Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) Acute intestinal injury will be defined a radiological, operative or post-mortem evidence of gut ischaemia.
Clinical events: A composite endpoint Organ Injury, Mortality and Sepsis Time (days) measured from the start of surgery to discharge from hospital (up to 90 days) As above for description of organ injury, mortality and sepsis
Mechanism study: microRNA isolation in adipose tissue biopsies At time of surgery Adipose tissue collected from epicardial fat at time of surgery. The findings will be represented by the frequency (%) of identified microRNA.
Mechanism study: Measurement of histone acetylation in urine samples Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively. The findings will be reported as acetylated H3 (ug/mg) over time (hours)
Mechanism study: Mitochondrial function measured in adipose tissue biopsies At time of surgery 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: Measurement of microvesicles in urine samples Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively. Identification of microvesicles. The findings will be represented by the frequency (%) of each identified microvesicle.
Mechanism study: Measurement of gene expression in urine samples Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively. Whole genome sequencing will be achieved through ATAC sequencing. The identified genes will be characterised by average expression count over ATAC.
Trial Locations
- Locations (1)
University of Leicester
🇬🇧Leicester, Leicestershire, United Kingdom