Coronary Artery Bypass SurgeryPhase 4NCT00244283
A Comparison of Two Anaesthetic Methods of Protecting Heart Tissue During Cardiac Surgery
A Phase 4 study testing Sevoflurane and High thoracic epidural analgesia in people with Coronary Artery Bypass Surgery, run by Golden Jubilee National Hospital at 1 site in United Kingdom.
Trial summary
To compare two different methods of protecting heart muscle from damage caused by a decreased blood supply. Exposure to the anaesthetic agent sevoflurane can allow the heart muscle to resist longer periods of low blood or oxygen supply without sustaining the amount of damage that it would otherwise expect to. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Coronary Artery Bypass Surgery
- What is being tested?
- Sevoflurane and High thoracic epidural analgesia
- Type of treatment
- Surgery or procedure
- How many people
- 150 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2006to Jan 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients presenting for elective CABG operations, with >40 % left ventricular ejection fraction, aged 40-80.
Who cannot join
- Patients at risk of epidural haematomas (i.e. platelets <100, coagulopathies, on anticoagulant therapies, INR>1.4) or unsuited to HTEA (patient refusal, spinal deformities).
- Patients on drugs shown to manipulate the preconditioning phenomenon will also be excluded. This includes those on diazoxide, nicorandil, oral sulfonylureas and theophyllines.
- Patients with preoperative ECG morphologies likely to make interpretation difficult or impossible including: left bundle branch block, cardiac pacemaker dependence.
- Haemodynamically compromised patients requiring inotropic or balloon pump support preoperatively.
- Significant valvular disease. Preoperative elevated levels of troponin I or CKMB. Unstable angina or angina in 24 hours preop
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Golden Jubilee National Hospital
Glasgow, G81 4HX
Martin F McCormick, MB ChB, 44 141 951 5600, Martin.McCormick@gjnh.scot.nhs.uk
Stefan Schraag, MD PhD, 44 141 951 5609, Stefan.Schraag@gjnh.scot.nhs.uk
About this study
Official title: A Comparison of Myocardial Protection Using Preconditioning With Sevoflurane Against High Thoracic Epidural Analgesia for CABG Surgery
To compare two different methods of protecting heart muscle from damage caused by a decreased blood supply. Exposure to the anaesthetic agent sevoflurane can allow the heart muscle to resist longer periods of low blood or oxygen supply without sustaining the amount of damage that it would otherwise expect to. The use of thoracic epidural analgesia improves the blood flow to the heart muscle and has also been shown to reduce the amount of damage the heart muscle may otherwise sustain. The aim of this study is to compare these two methods.
Read the detailed description
Coronary artery bypass grafting (CABG) is a common procedure performed to improve blood flow to the heart in patients with severe ischaemic heart disease. Commonly, the heart has to be stopped to allow this procedure to be performed and this is often achieved with cooling the heart and perfusing it with a solution that stops the activity of the heart muscle. These techniques stop the heart from beating which allows the surgery to be performed and also reduce the oxygen requirements of the heart. This in turn reduces the damage the heart suffers from the reduced blood flow to it which occurs while the arteries are being operated on. Unfortunately, however, these techniques do not completely eliminate the risk of heart muscle damage and so new methods of further reducing damage to the heart are continually being investigated. Two methods relating to the anaesthetic techniques used have recently been identified as potentially of benefit in this regard - the use of volatile anaesthetic agents and the use of high thoracic epidural analgesia.
Volatile anaesthetic agents have been extensively investigated in the past few years with regard to their apparent ability to mimic ischaemic preconditioning. Ischaemic preconditioning refers to the phenomenon that if heart tissue is exposed to frequent, short episodes of reduced blood or oxygen supply, followed by a longer spell, the heart is likely to suffer a smaller area of damage than if it had never been exposed to the brief ischaemic spells. This can be related clinically to the observation that patients with angina, who subsequently suffer a heart attack, have a better prognosis than those patients who suffer a heart attack without ever experiencing angina prior to the event. There have been numerous studies demonstrating that the volatile anaesthetic agents (isoflurane, sevoflurane, desflurane) appear to mimic this phenomenon, both in animal and human models. Numerous studies have demonstrated favourable postoperative blood concentrations of cardiac troponin I (a sensitive marker of heart damage), CK-MB (another marker of heart damage), atrial and brain natriueretic peptides (markers of heart function) compared to those who did not receive preconditioning. It has therefore been suggested that this may improve outcome following cardiac surgery.
High thoracic epidural analgesia (HTEA) has also been shown to be beneficial following cardiac surgery. This involves placing a small catheter near the nerves as they leave the spinal cord. Local anaesthetic ccan be administered down this catheter to numb the areas of the body supplied by these nerves. This provides very good pain relief and is widely used in our hospital for this operation. It has been shown to be associated with a shorter time of required artificial ventilation compared to standard pain relief with drugs such as morphine. It has also been suggested that it may influence outcome with improved heart function following the operation compared to those without HTEA. It appears to do this by improving the blood flow to the heart. It has also been associated with a lower postoperative concentration of cardiac troponin , CK-MB, atrial and brain natriuretic peptides. There has not been any direct comparison of the two techniques, however, to assess if one is superior to the other, or if the benefits of the two techniques are additive.
Comparison:
This study aims to assess if one technique confers more benefit than the other and if the benefits are additive. This is important as many centres do not use thoracic epidural analgesia for cardiac surgery and not all clinicians currently use volatile anaesthetics for cardiac surgery.
- Conditions
- Coronary Artery Bypass Surgery
- Being tested
- Sevoflurane, High thoracic epidural analgesia
- Keywords
- Myocardial preconditioning, anesthetics, epidural anesthesia, sevoflurane, NT proBNP
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SevofluraneDrug
High thoracic epidural analgesiaProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentration of NT-proBNP as a biochemical marker of ventricular dysfunction
Secondary outcomes (2)
Changes in plasma measurements of cardiac troponin I and CK-MB from baseline over the first two poatoperative days.
Cardiac morbidity/ mortality as defined by incidence of death, inotrope requirements, arrhythmias, left ventricular dysfunction, pulmonary oedema or myocardial infarction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2005 (estimated)
- Study startJan 2006
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery Bypass SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants
Sponsor and investigators
- Lead sponsor
- Golden Jubilee National Hospital
- Sponsor type
- Other government
- Collaborators
- European Society for Intravenous Anaesthesia
- Investigators
- Stefan Schraag, MD PhD, Study director, Golden Jubilee National HospitalMartin F McCormick, MB ChB, Principal investigator, Golden Jubilee National Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00244283
- Sponsor's protocol ID
- gjnh/mccormick/01
- Other IDs
- EUDRACT no. 2005-004398-76
- Status last verified
- Oct 2005
- First submitted
- 24 Oct 2005
- Last updated
- 26 Oct 2005
- Results posted
- No
Publications
Julier K, da Silva R, Garcia C, Bestmann L, Frascarolo P, Zollinger A, Chassot PG, Schmid ER, Turina MI, von Segesser LK, Pasch T, Spahn DR, Zaugg M. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo-controlled, multicenter study. Anesthesiology. 2003 Jun;98(6):1315-27. doi: 10.1097/00000542-200306000-00004.
PubMed 12766638Berendes E, Schmidt C, Van Aken H, Hartlage MG, Wirtz S, Reinecke H, Rothenburger M, Scheld HH, Schluter B, Brodner G, Walter M. Reversible cardiac sympathectomy by high thoracic epidural anesthesia improves regional left ventricular function in patients undergoing coronary artery bypass grafting: a randomized trial. Arch Surg. 2003 Dec;138(12):1283-90; discussion 1291. doi: 10.1001/archsurg.138.12.1283.
PubMed 14662525
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparison of Myocardial Protection Using Preconditioning With Sevoflurane Against High Thoracic Epidural Analgesia for CABG Surgery
- ClinicalTrials.gov ID
- NCT00244283
- Acronym / sponsor ID
- gjnh/mccormick/01
- Conditions
- Coronary Artery Bypass Surgery
- Keywords
- Myocardial preconditioning, anesthetics, epidural anesthesia, sevoflurane, NT proBNP
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants
- Lead sponsor
- Golden Jubilee National HospitalOther government
- Collaborators
- European Society for Intravenous Anaesthesia
- Study start
- Jan 2006
- Study completion
- Jan 2008
- First posted
- 26 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare two different methods of protecting heart muscle from damage caused by a decreased blood supply. Exposure to the anaesthetic agent sevoflurane can allow the heart muscle to resist longer periods of low blood or oxygen supply without sustaining the amount of damage that it would otherwise expect to. The use of thoracic epidural analgesia improves the blood flow to the heart muscle and has also been shown to reduce the amount of damage the heart muscle may otherwise sustain. The aim of this study is to compare these two methods.
Detailed description
Coronary artery bypass grafting (CABG) is a common procedure performed to improve blood flow to the heart in patients with severe ischaemic heart disease. Commonly, the heart has to be stopped to allow this procedure to be performed and this is often achieved with cooling the heart and perfusing it with a solution that stops the activity of the heart muscle. These techniques stop the heart from beating which allows the surgery to be performed and also reduce the oxygen requirements of the heart. This in turn reduces the damage the heart suffers from the reduced blood flow to it which occurs while the arteries are being operated on. Unfortunately, however, these techniques do not completely eliminate the risk of heart muscle damage and so new methods of further reducing damage to the heart are continually being investigated. Two methods relating to the anaesthetic techniques used have recently been identified as potentially of benefit in this regard - the use of volatile anaesthetic agents and the use of high thoracic epidural analgesia.
Volatile anaesthetic agents have been extensively investigated in the past few years with regard to their apparent ability to mimic ischaemic preconditioning. Ischaemic preconditioning refers to the phenomenon that if heart tissue is exposed to frequent, short episodes of reduced blood or oxygen supply, followed by a longer spell, the heart is likely to suffer a smaller area of damage than if it had never been exposed to the brief ischaemic spells. This can be related clinically to the observation that patients with angina, who subsequently suffer a heart attack, have a better prognosis than those patients who suffer a heart attack without ever experiencing angina prior to the event. There have been numerous studies demonstrating that the volatile anaesthetic agents (isoflurane, sevoflurane, desflurane) appear to mimic this phenomenon, both in animal and human models. Numerous studies have demonstrated favourable postoperative blood concentrations of cardiac troponin I (a sensitive marker of heart damage), CK-MB (another marker of heart damage), atrial and brain natriueretic peptides (markers of heart function) compared to those who did not receive preconditioning. It has therefore been suggested that this may improve outcome following cardiac surgery.
High thoracic epidural analgesia (HTEA) has also been shown to be beneficial following cardiac surgery. This involves placing a small catheter near the nerves as they leave the spinal cord. Local anaesthetic ccan be administered down this catheter to numb the areas of the body supplied by these nerves. This provides very good pain relief and is widely used in our hospital for this operation. It has been shown to be associated with a shorter time of required artificial ventilation compared to standard pain relief with drugs such as morphine. It has also been suggested that it may influence outcome with improved heart function following the operation compared to those without HTEA. It appears to do this by improving the blood flow to the heart. It has also been associated with a lower postoperative concentration of cardiac troponin , CK-MB, atrial and brain natriuretic peptides. There has not been any direct comparison of the two techniques, however, to assess if one is superior to the other, or if the benefits of the two techniques are additive.
Comparison:
This study aims to assess if one technique confers more benefit than the other and if the benefits are additive. This is important as many centres do not use thoracic epidural analgesia for cardiac surgery and not all clinicians currently use volatile anaesthetics for cardiac surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients presenting for elective CABG operations, with >40 % left ventricular ejection fraction, aged 40-80.
Key exclusion criteria (5 listed)
- Patients at risk of epidural haematomas (i.e. platelets <100, coagulopathies, on anticoagulant therapies, INR>1.4) or unsuited to HTEA (patient refusal, spinal deformities).
- Patients on drugs shown to manipulate the preconditioning phenomenon will also be excluded. This includes those on diazoxide, nicorandil, oral sulfonylureas and theophyllines.
- Patients with preoperative ECG morphologies likely to make interpretation difficult or impossible including: left bundle branch block, cardiac pacemaker dependence.
- Haemodynamically compromised patients requiring inotropic or balloon pump support preoperatively.
- Significant valvular disease. Preoperative elevated levels of troponin I or CKMB. Unstable angina or angina in 24 hours preop
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sevoflurane | Drug | – |
| High thoracic epidural analgesia | Procedure or surgery | – |
Primary outcome
Plasma concentration of NT-proBNP as a biochemical marker of ventricular dysfunction
2 secondary outcomes
Changes in plasma measurements of cardiac troponin I and CK-MB from baseline over the first two poatoperative days.
Cardiac morbidity/ mortality as defined by incidence of death, inotrope requirements, arrhythmias, left ventricular dysfunction, pulmonary oedema or myocardial infarction
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2005.
- Background: PubMed 12766638Julier K, da Silva R, Garcia C, Bestmann L, Frascarolo P, Zollinger A, Chassot PG, Schmid ER, Turina MI, von Segesser LK, Pasch T, Spahn DR, Zaugg M. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo-controlled, multicenter study. Anesthesiology. 2003 Jun;98(6):1315-27. doi: 10.1097/00000542-200306000-00004.
- Background: PubMed 14662525Berendes E, Schmidt C, Van Aken H, Hartlage MG, Wirtz S, Reinecke H, Rothenburger M, Scheld HH, Schluter B, Brodner G, Walter M. Reversible cardiac sympathectomy by high thoracic epidural anesthesia improves regional left ventricular function in patients undergoing coronary artery bypass grafting: a randomized trial. Arch Surg. 2003 Dec;138(12):1283-90; discussion 1291. doi: 10.1001/archsurg.138.12.1283.
Related trials for Coronary Artery Bypass Surgery
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
RecruitingEarly Phase 1
Thiamine Intervention and Coronary Artery Bypass Grafting
Coronary Heart Disease, Coronary Artery Bypass Grafting
Not yet recruitingObservational study
Preoperative Gastric Ultrasound and Anaesthetic Management in Patients Undergoing Coronary Artery Bypass Grafting
Preoperative Fasting, Pulmonary Aspiration During Anesthetic Induction
Active, not recruiting
Investigation of the Effects of Respiratory Muscle Training Combined With Otago Exercises in Elderly Patients Undergoing Coronary Artery Bypass Graft Surgery
Coronary Artery Bypass Graft (CABG)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Schraag, MD PhD study director
Golden Jubilee National Hospital
Martin F McCormick, MB ChB principal investigator
Golden Jubilee National Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sevoflurane and High thoracic epidural analgesia in people with Coronary Artery Bypass Surgery, run by Golden Jubilee National Hospital at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Oct 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Martin F McCormick, MB ChB (44 141 951 5600, Martin.McCormick@gjnh.scot.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma concentration of NT-proBNP as a biochemical marker of ventricular dysfunction. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00244283, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2005.