Clinical trial NCT04015973: 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
Overall status: RECRUITING
Phase: NA
Conditions: Cardiac Valve Disease
Coronary Artery Disease
Organ Failure, Multiple
Lead sponsor: University of Leicester
Sponsor class: OTHER
First posted: 2019-07-11
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Unblinded randomised controlled trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change of Serum Creatinine level
timeFrame: Baseline, 0-6, 6-12, 24, 48, 72, and up to 96 hours post-operatively
measure: Change of Serum Troponin I level
timeFrame: Baseline, 0-6, 6-12, 24, 48 and 72 hours post-operatively
Secondary outcomes:
measure: Post-surgery organ injury: Sepsis-related Organ Failure
timeFrame: Baseline, pre-operatively, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively
measure: Post-surgery organ injury: Kidney Injury (Urinary Biomarkers) - NGAL (Neutrophil gelatinase associated lipocalcin)
timeFrame: Baseline, 1 day pre-op, 6-12, 24 and 48 hours post-operatively
measure: Post-surgery organ injury: Kidney Injury (Urinary Biomarkers) - microRNA (Neutrophil gelatinase associated lipocalcin)
timeFrame: Baseline, 1 day pre-op, 6-12, 24 and 48 hours post-operatively
measure: Post-surgery organ injury: Kidney Injury
timeFrame: Daily for 5 days from Baseline
measure: Post-surgery organ injury: Kidney Injury
timeFrame: At 6 weeks and then 3 months post-surgery
measure: Post-surgery organ injury: Lung Injury using the Berlin ARDS Score
timeFrame: Baseline, immediately pre-surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively
measure: Post-surgery organ injury: GI Tract injury (Biomarker) - AST (Aspartate Transaminase)
timeFrame: Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
measure: Post-surgery organ injury: GI Tract injury (Biomarker) - ALT (Alanine Transaminase)
timeFrame: Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
measure: Post-surgery organ injury: GI Tract injury (Biomarker) - Bilirubin
timeFrame: Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
measure: Post-surgery organ injury: GI Tract injury (Biomarker) - Alkaline Phosphatase
timeFrame: Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
measure: Post-surgery organ injury: GI Tract injury (Biomarker) - Serum Amylase
timeFrame: Baseline, pre-assessment, pre-operatively, 0-6 and at 6-12, 24, 48, 72 and 96 hours post-operatively.
measure: Assessment of resource use: Extubation
timeFrame: Time (hours) measured from the start of surgery to extubation (up to 30 days)
measure: Assessment of resource use: Intensive Care Unit
timeFrame: Time (hours) measured from the start of surgery to discharge from ICU (up to 30 days)
measure: Assessment of resource use: Hospital Stay
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Sepsis
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Peak lactate
timeFrame: Within 24 hours of surgery
measure: Clinical events: Acute Lung Injury
timeFrame: Baseline, immediately pre-surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-operatively
measure: Clinical events: Low cardiac output
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Stroke
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Acute Liver Injury - AST (Aspartate Transaminase)
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Acute Liver Injury - ALT (Alanine Transaminase)
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Acute Liver Injury - Bilirubin
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Acute Liver Injury - Alkaline Phosphatase
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Acute Liver Injury - Serum Amylase
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Acute Intestinal Injury
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Clinical events: Rate of mortality
timeFrame: Within 30-days from surgery and at 1 year from surgery
measure: Clinical events: A composite endpoint Organ Injury, Mortality and Sepsis
timeFrame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
measure: Bleeding and Transfusion
timeFrame: Blood loss at 6 hours post-operatively
measure: Mechanism study: Mitochondrial function of microvessels from tissue biopsies
timeFrame: At time of surgery
measure: Mechanism study: microRNA isolation of microvessels from tissue biopsies
timeFrame: At time of surgery
measure: Mechanism study: Chromatin Immunoprecipitation (ChIP) of microvessels from tissue biopsies
timeFrame: At time of surgery
measure: Mechanism study: Mitochondrial function measured in right atrium myocardium tissue biopsies
timeFrame: At time of surgery
measure: Mechanism study: microRNA isolation in right atrium myocardium tissue biopsies
timeFrame: At time of surgery
measure: Mechanism study: Chromatin Immunoprecipitation (ChIP) in right atrium myocardium tissue biopsies
timeFrame: At time of surgery
measure: Mechanism study: Mitochondrial function measured in adipose tissue biopsies
timeFrame: At time of surgery
measure: Mechanism study: microRNA isolation in adipose tissue biopsies
timeFrame: At time of surgery
measure: Mechanism study: Chromatin Immunoprecipitation (ChIP) in adipose tissue biopsies
timeFrame: At time of surgery
measure: Mechanism study: Measurement of microvesicles in urine samples
timeFrame: Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively.
measure: Mechanism study: Measurement of microRNA in urine samples
timeFrame: Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively.
measure: Mechanism study: Measurement of histone acetylation in urine samples
timeFrame: Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively.
measure: Mechanism study: Measurement of gene expression in urine samples
timeFrame: Baseline,1 day before surgery, 6-12, 24 and 48 hours post-operatively.
Other outcomes:
measure: Body Composition: Bone Density Scan (DEXA)
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Imaging Assessment of Cardiometabolic Status: Trans-Oesophageal Echo
timeFrame: At time of surgery
measure: Imaging Assessment (optional): Cardiac Magnetic Resonance Imaging - Cardiac Function
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Imaging Assessment (optional): Cardiac Magnetic Resonance Imaging - Cardiac adiposity content
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Imaging Assessment (optional): Cardiac Magnetic Resonance Imaging - Visceral adiposity content
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Fitness, Frailty and Muscle Strength: Six Minute Walk Test
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Fitness, Frailty and Muscle Strength: Hand Grip Test
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Fitness, Frailty and Muscle Strength: PRISMA-7 Questionnaire
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Activity Levels and Sleep: Accelerometer Assessments
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Comorbidity and Inflammation - CRP (C-Reactive-Protein) assay (Abcam)
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Comorbidity and Inflammation - NT-proBNP (Abcam)
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Comorbidity and Inflammation - estimated Glomerular Filtration Rate
timeFrame: Baseline, pre-assessment and 3 months post-surgery
measure: Endothelial function: Blood samples
timeFrame: Baseline, 6-12 and 48 hours post-surgery
measure: Endothelial function: Reactive Hyperaemia Peripheral Arterial Tonometry (RH-PAT)
timeFrame: 1 day before surgery and 24 hours post-surgery
measure: Endothelial function: Global endothelial dysfunction
timeFrame: 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)
Locations:
city: Leicester
country: United Kingdom
facility: University of Leicester
state: Leicestershire
Study officials:
affiliation: BHF Professor of Cardiac Surgery, University of Leicester
name: Gavin J Murphy, MD
role: STUDY_CHAIR
affiliation: Associate Professor, University of Leicester
name: Mustafa Zakkar, PhD
role: PRINCIPAL_INVESTIGATOR
References: