Comparison Between Propofol and Inhalational Anaesthetic Agents on Cardiovascular Outcomes Following Cardiac Surgery (COPIA)

Comparison Between Propofol and Inhalational Anaesthetic Agents on Cardiovascular Outcomes Following Cardiac Surgery - a Randomised Controlled Feasibility Trial

The objective of this research proposal is to find out whether comparing the two different anaesthetic maintenance techniques (Propofol vs volatile anaesthetics) in adult patients undergoing heart surgery is practical for the anaesthetist treating the patients and whether it is feasible for the research team to recruit patients and follow them up after the operation.

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Diseases; Coronary Heart Disease
• Intervention / Treatment: Drug: Isoflurane, Sevoflurane or Desflurane; Drug: Propofol

Detailed Description

All patients undergoing heart bypass surgery are given anaesthetics during the operation. There are two types of anaesthetic commonly given to patients undergoing heart bypass surgery.

Propofol is an anaesthetic that is delivered into the patient's vein. Other anaesthetics which are inhaled include Isoflurane, Sevoflurane and Desflurane and these are called volatile anaesthetics. Preliminary studies over the past ten years suggests that maintenance of general anaesthesia using only volatile anaesthetics has the potential to improve health outcomes after bypass surgery, when compared with propofol.

Volatile anaesthetics have been shown to protect the heart, the kidneys and the brain, however results of studies have been inconclusive. Currently both volatile anaesthetics and propofol are used equally in clinical practice in the UK.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kimberley Potter; Phone Number: 2505 02079272505; Email: kimberley.potter@LSHTM.ac.uk
• Study Contact Backup: Name: Richard Evans; Phone Number: 2665 02072972665; Email: richard.evans@LSHTM.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Kings College Hospital NHS Foundation Trust
    • Contact: Gudrun Kunst
    • Principal Investigator: Gudrun Kunst
  • London, United Kingdom, SE1 7EH
    • Not yet recruiting
    • St Thomas' Hospital
    • Contact: Martin John
    • Principal Investigator: Martin John

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients (male and female) aged 18 years and above
• Written informed consent to participate
• Patients undergoing Coronary Artery Bypass Graft (CABG) surgery on Cardiopulmonary bypass (CPB) with or without valve surgery
• Additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 5 or higher

Exclusion Criteria:

• Pregnant or lactating women
• Allergy to propofol
• Previous diagnosis or suspected malignant hyperthermia
• Patients with a known sensitivity to any of the IMPs or other halogenated anaesthetics
• Concomitant therapy with glibenclamide or nicorandil (medications that may interfere with preconditioning)
• Inclusion in another clinical trial of an investigational medicinal product within the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Volatile anaesthetics arm; Patients randomised to receive volatile anaesthetics will receive either isoflurane, sevoflurane or desflurane during the surgical procedure.	Drug: Isoflurane, Sevoflurane or Desflurane; The volatile anaesthetic agent will be administered via inhalation, i.e. ventilation through alveolar membrane in lungs) during the maintenance of anaesthesia. During CPB the volatile anaesthetic agent will be administered through the oxygenator oxygen inflow of the CPB machine. The maintenance dose of the volatile anaesthetic agent will be titrated to doses deemed necessary in order to provide sufficient depth of anaesthesia and blood pressure. The administration of the volatile anaesthetic agent will be started after induction of anaesthesia and it will be ended at the end of surgery, before the patient is transferred to the CCU.
ACTIVE_COMPARATOR: Propofol anaesthetics arm; Patients randomised to receive propofol will not receive any volatile anaesthetics during the surgical procedure.	Drug: Propofol; Patients will receive propofol only during the surgical procedure. The maintenance dose of the propofol infusion will be titrated to doses deemed necessary in order to provide sufficient depth of anaesthesia (titrated to a depth of anaesthesia with BIS 30-60) and mean arterial pressure (MAP) of 50-80mmHg by the treating anaesthetist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	To identify whether it is feasible to recruit up to 50 patients across 2 tertiary cardiac surgery centres within approximately 10 months.	Collected over the recruitment period of 10 months
To identify barriers to recruitment.	This data will be completed on a screening log.	Collected over the recruitment period of 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of maintaining follow-up rates of over 95%	This data will be gathered in the trial database.	Collected over the recruitment period of 10 months
Assessment of effectiveness of patient identification and screening processes	To record the number of patients screened and potentially eligible for the trial at the two tertiary cardiac surgery centres within a period of 10 months. This data will be gathered on the screening log.	Collected over the recruitment period of 10 months
To investigate whether it is feasible to recruit at least 10% of all potentially eligible patients at the two tertiary cardiac surgery centres within a period of 10 months.	This data will be gathered on screening logs and in the randomisation system.	Collected over the recruitment period of 10 months
To investigate whether it is feasible to maintain routine data collection and follow up rates greater than 90% over the trial period.	This data will be gathered in the randomisation site and trial database.	Collected over the full trial period of 24 months
To investigate whether it is feasible to achieve 95% data collection of Low Cardiac Output Syndrome for the full trial over the trial period.	This data will be gathered in the trial database.	Collected over the full trial period of 24 months
To investigate whether it is feasible to achieve 95% data collection of Myocardial injury, assessed by ischaemic serum markers: hsTnT, MyC, for the full trial over the trial period.	This data will be gathered in the trial database.	Preop, 6 hrs after arrival in CCU, and postop day 1 and 2. Collected over the full trial period of 24 months
To investigate whether it is feasible to achieve 90% data collection of MACCE (stroke, non-fatal myocardial infarction, death from any cause) for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at 30 days post op.
To investigate whether it is feasible to achieve 90% data collection of Cardiac related mortality at 30 days for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at 30 days post op.
To investigate whether it is feasible to achieve 90% data collection of Postoperative in hospital atrial fibrillation requiring treatment for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at 30 days post op.
To investigate whether it is feasible to achieve 90% data collection of Acute Kidney Injury (according to Kidney Disease: Improving Global Outcomes guidelines) for the full trial over the trial period.	AKI will be confirmed by a 1.5 - 1.9 increase of serum creatinine from baseline or an absolute value rise of creatine greater than 0.3mg/dl (27mmol/L) from baseline. This data will be gathered in the trial database.	Data collected at 30 days post op.
To investigate whether it is feasible to achieve 90% data collection of In-hospital postoperative delirium (assessed by the confusion assessment method) for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at 30 days post op.
To investigate whether it is feasible to achieve 90% data collection of Respiratory complications needing prolonged ventilation (>24 hours) for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at 30 days post op.
To investigate whether it is feasible to achieve 90% data collection of Length of stay in the critical care unit (CCU) for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at 30 days post op.
To investigate whether it is feasible to achieve 90% data collection of Length of hospital stay for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at 30 days post op.
To investigate whether it is feasible to achieve 90% data collection of WHO Disability Assessment Schedule (WHODAS) for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at 30 days post op.
To investigate whether it is feasible to achieve 90% data collection of Quality of Life Questionnaire (Euroqol, EQ-5D-5L) for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at Baseline and 30 days postoperative
To investigate whether it is feasible to achieve 90% data collection of Days alive and at home for the full trial over the trial period.	This data will be gathered in the trial database.	Data collected at 30 days postoperative

Collaborators and Investigators

• Sponsor: King's College Hospital NHS Trust
• Collaborators: London School of Hygiene and Tropical Medicine; Guy's and St Thomas' NHS Foundation Trust
• Investigators: Principal Investigator: Dr Gudrun Kunst, King's College Hospital NHS Trust

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 20, 2019
• Primary Completion (ANTICIPATED): November 30, 2021
• Study Completion (ANTICIPATED): January 31, 2022

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (ACTUAL): July 31, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Cardioprotection; Anaesthesia; Coronary Artery Bypass Surgery
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Cardiovascular Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Inhalation; Propofol; Desflurane; Sevoflurane; Isoflurane
• Other Study ID Numbers: KCH-PRO:19/001; 2019-000171-16 (EUDRACT_NUMBER); 216646 (OTHER: IRAS ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymous participant data may be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No