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

• ClinicalTrials.gov Identifier: NCT04039854
• Recruitment Status: Unknown
• First Posted: July 31, 2019
• Last Update Posted: February 24, 2021
• Sponsor: King's College Hospital NHS Trust
• Collaborators: London School of Hygiene and Tropical Medicine; Guy's and St Thomas' NHS Foundation Trust
• Information provided by (Responsible Party): King's College Hospital NHS Trust

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Coronary Heart Disease; Cardiovascular Diseases	Drug: Isoflurane, Sevoflurane or Desflurane; Drug: Propofol	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Comparison Between Propofol and Inhalational Anaesthetic Agents on Cardiovascular Outcomes Following Cardiac Surgery - a Randomised Controlled Feasibility Trial
• Actual Study Start Date: November 20, 2019
• Estimated Primary Completion Date: November 30, 2021
• Estimated Study Completion Date: January 31, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Feasibility of maintaining follow-up rates of over 95% [ Time Frame: Collected over the recruitment period of 10 months ]
   This data will be gathered in the trial database.
2. Assessment of effectiveness of patient identification and screening processes [ Time Frame: Collected over the recruitment period of 10 months ]
   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.
3. 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. [ Time Frame: Collected over the recruitment period of 10 months ]
   This data will be gathered on screening logs and in the randomisation system.
4. To investigate whether it is feasible to maintain routine data collection and follow up rates greater than 90% over the trial period. [ Time Frame: Collected over the full trial period of 24 months ]
   This data will be gathered in the randomisation site and trial database.
5. To investigate whether it is feasible to achieve 95% data collection of Low Cardiac Output Syndrome for the full trial over the trial period. [ Time Frame: Collected over the full trial period of 24 months ]
   This data will be gathered in the trial database.
6. 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. [ Time Frame: Preop, 6 hrs after arrival in CCU, and postop day 1 and 2. Collected over the full trial period of 24 months ]
   This data will be gathered in the trial database.
7. 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. [ Time Frame: Data collected at 30 days post op. ]
   This data will be gathered in the trial database.
8. 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. [ Time Frame: Data collected at 30 days post op. ]
   This data will be gathered in the trial database.
9. 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. [ Time Frame: Data collected at 30 days post op. ]
   This data will be gathered in the trial database.
10. 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. [ Time Frame: Data collected at 30 days post op. ]
    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.
11. 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. [ Time Frame: Data collected at 30 days post op. ]
    This data will be gathered in the trial database.
12. 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. [ Time Frame: Data collected at 30 days post op. ]
    This data will be gathered in the trial database.
13. 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. [ Time Frame: Data collected at 30 days post op. ]
    This data will be gathered in the trial database.
14. To investigate whether it is feasible to achieve 90% data collection of Length of hospital stay for the full trial over the trial period. [ Time Frame: Data collected at 30 days post op. ]
    This data will be gathered in the trial database.
15. 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. [ Time Frame: Data collected at 30 days post op. ]
    This data will be gathered in the trial database.
16. 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. [ Time Frame: Data collected at Baseline and 30 days postoperative ]
    This data will be gathered in the trial database.
17. 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. [ Time Frame: Data collected at 30 days postoperative ]
    This data will be gathered in the trial database.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Kimberley Potter; 02079272505 ext 2505; kimberley.potter@LSHTM.ac.uk

Contact: Richard Evans; 02072972665 ext 2665; richard.evans@LSHTM.ac.uk

Locations

United Kingdom

St Thomas' Hospital; Not yet recruiting

London, United Kingdom, SE1 7EH

Contact: Martin John

Principal Investigator: Martin John

Kings College Hospital NHS Foundation Trust; Recruiting

London, United Kingdom, SE5 9RS

Contact: Gudrun Kunst

Principal Investigator: Gudrun Kunst

Sponsors and Collaborators

King's College Hospital NHS Trust

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

More Information

• Responsible Party: King's College Hospital NHS Trust
• ClinicalTrials.gov Identifier: NCT04039854
• Other Study ID Numbers: KCH-PRO:19/001; 2019-000171-16 ( EudraCT Number ); 216646 ( Other Identifier: IRAS ID )
• First Posted: July 31, 2019
• Last Update Posted: February 24, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymous participant data may be shared with other researchers

• 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

Keywords provided by King's College Hospital NHS Trust:

Anaesthesia; Coronary Artery Bypass Surgery; Cardioprotection

Additional relevant MeSH terms:

Cardiovascular Diseases; Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Propofol; Sevoflurane; Desflurane; Isoflurane; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Anesthetics, Inhalation