Plain English Summary
Background and study aims
Almost 2.3 million people in the UK are living heart disease and > 36,000 cardiac surgery operations are carried out each year. During surgery the heart is isolated from the rest of the circulation and a heart-lung machine is used to supply oxygen to the blood and pump it around the body. The heart is stopped and provided with nutrients by a cardioplegic solution that is injected directly into the heart arteries. This allows the surgeon to operate on the heart while it is still and not filled with blood, but looking after the heart in this way during surgery is not ideal. The heart muscle can become short of oxygen, and when the heart is restarted, and blood starts to flow again the muscle can be harmed.
The damage is believed to be caused mainly by the formation of highly reactive molecules known as ‘free radicals’ in the heart muscle during the time it is short of oxygen. Propofol is a general anaesthetic widely used in cardiac surgery and research suggests that propofol could protect the heart muscle against damage from free radicals. We want to investigate whether adding propofol to the cardioplegic solution in patients having isolated coronary artery bypass grafting (CABG) surgery using the heart-lung machine is beneficial and if the benefit is greater the more propofol that is used.
Who can participate?
Anyone having elective or urgent isolated CABG with cardiopulmonary bypass (CPB)
What does the study involve?
During heart surgery, it is important that the heart be kept still while the surgical team are working on it. This is done by injecting a solution called cardioplegia. We believe that adding propofol to this solution will protect the heart muscle during its period of inactivity, and this in turn may lead to fewer complications after the operation.
The purpose of this study is to compare the results from three different approaches: adding a low dose of propofol to the cardioplegia solution, adding a higher dose, and not adding any at all. Propofol is widely used as an anaesthetic, and you will receive this anyway as part of usual general anaesthesia.
What are the possible benefits and risks of participating?
Whilst we cannot promise taking part in this study will help you, the information gained will help us make decisions which could potentially improve the treatment of heart surgery patients in the future.
Patients in all groups are at risk of operative and postoperative complications, your doctor will discuss this with you prior to your operation and inform you of the possible side effects of propofol as part of routine care. However, no extra complications are expected due to adding the propofol to the cardioplegia solution with propofol, but if you would like further information, please ask a member of the research team.
Where is the study run from?
The University of Bristol is the sponsor for this study and has overall responsibility for the study. The study is managed by the Bristol Trials Centre (CTEU).
When is the study starting and how long is it expected to run for?
August 2018 to May 2021
Who is funding the study?
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC)
Who is the main contact?
Rachael Heys
Prompt2-trial@bristol.ac.uk
Trial website
Contact information
Type
Public
Primary contact
Miss Rachael Heys
ORCID ID
Contact details
Bristol Trials Centre (CTEU)
Bristol Medical School
University of Bristol
Bristol Royal Infirmary
Level 7
Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom
-
Prompt2-trial@bristol.ac.uk
Additional identifiers
EudraCT number
2018-000169-35
ClinicalTrials.gov number
Nil known
Protocol/serial number
CPMS 37464
Study information
Scientific title
Efficacy of propofol-supplemented cardioplegia on biomarkers of organ injury in patients having cardiac surgery using cardiopulmonary bypass: Propofol cardioplegia for myocardial protection randomised controlled trial: the PROMPT2 Study
Acronym
Study hypothesis
Adding propofol to the cardioplegic solution used during cardiac surgery reduces organ damage
Ethics approval
Approved 12/10/2018, South Central - Berkshire B Research Ethics Committee (Whitefriars, Level 3, Block B Lewins Mead, Bristol BS1 2NT; nrescommittee.southcentral-berkshire@nhs.net; 0207 104 8059), ref: 18/SC/0472
Study design
Interventional Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Reperfusion injury of the heart following coronary artery bypass grafting (CABG) surgery
Intervention
Study patients will be randomly allocated in a 1:1:1 ratio to one of the following:
Placebo: Blood cardioplegia with sham supplementation (normal saline 0.9% weight/volume sodium chloride, NaCl),
Propofol - LD: Blood cardioplegia with low dose (6mcg/ml) propofol supplementation
Propofol - HD: Blood cardioplegia with high dose (12mcg/ml) propofol supplementation
The total duration of treatment is for as long as the cardiac surgery takes.
The follow-up period is at 3 and 12 months, by QoL questionnaires.
Randomisation will be carried out as close to the planned operation as possible, after eligibility has been confirmed and written informed consent given. Randomisation will be performed by a member of the research team not involved in data collection using a secure internet-based randomisation system ensuring allocation concealment. Randomisation will take place as soon as it is confirmed the surgery will go ahead, which is typically 30 minutes before the patient is taken to theatre. Patients will be allocated in a 1:1:1 ratio to either i) high dose propofol supplementation or ii) low dose propofol supplementation or iii) sham supplementation. The allocation will be computer-generated and stratified by centre. Baseline quality of life (QoL) will be collected from the patients prior to randomisation.
Intervention type
Drug
Phase
Phase II
Drug names
Propofol
Primary outcome measure
Myocardial injury, assessed by serial measurements of cTnT in serum from blood samples collected pre-operatively and during the first 48-hours post chest closure.
Secondary outcome measures
1. Systemic metabolic stress as measured by blood lactate at pre-op, 10 mins post cross clamp, 1, 6, 12, 24, 48 hours post chest closure
2. Renal function, as measured by creatinine in serum at pre-op, 1, 6, 12, 24, 48 hours post chest closure
3. Markers of Inflammation and oxidative stress as measured by tumour necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-8, IL-6 and myeloperoxidase (MPO) in serum (Bristol cohort only) at pre-op, 1, 6, 12, 24, 48 hours post chest closure
4. Blood pH at pre-op, 1, 6, 12, 24, 48 hours post chest closure
5. Investigate the association between cTnT and circulating level of cardiac -released microRNA-1 and exosomal microRNA-1 content at pre-op, 1, 6, 12, 24, 48 hours post chest closure.
6. Examine whether the association between cTnT and microRNA and exosomal microRNA-1 content differs between groups (i.e. differs with the propofol supplementation received) at pre-op, 1, 6, 12, 24, 48 hours post chest closure.
7. Length of intensive care unit (ICU) stay
8. Length of postoperative hospital stay
9. Clinical outcomes and serious adverse events, i.e. serious post-operative complications (e.g. MI, permanent stroke, acute kidney injury) and death from any cause.
10. QoL measured using the Coronary Revascularisation Outcome Questionnaire (CROQ) and the EQ-5D-5L questionnaire at baseline, 3-months and 12-months.
Overall trial start date
01/12/2017
Overall trial end date
01/01/2022
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged >= 18 years
2. Having elective or urgent isolated CABG with CPB
3. Ability to give informed consent
Women only:
4. Negative pregnancy test, or be surgically or post-menopausal for >12 months
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 240; UK Sample Size: 240
Participant exclusion criteria
Current participant exclusion criteria as of 20/05/2020:
1. Previous cardiac surgery
2. Planned concomitant procedure
3. Emergency or salvage operation
4. Long-term steroid therapy (taking tablets on a daily basis for at least 1 month prior to
surgery)
5. Pre-operative estimated glomerular filtration rate ≤ 30 ml/min/1.73m2
6. Current congestive heart failure
7. Left ventricular (LV) ejection fraction <30% (i.e. poor LV function)
8. Allergy to peanuts, eggs, egg products, soybeans or soy products
9. Already participating in another interventional clinical study
10. Prisoners
11. Patients taking immunosuppressants (e.g. methotrexate or azathioprine)
12. Patients known to have cTnT level >500 ng/l (or cTnI level >600 ng/l) in the last 4 days (prior to eligibility check)
Women only:
13. Breast feeding
Previous participant exclusion criteria:
1. Previous cardiac surgery
2. Planned concomitant procedure
3. Emergency or salvage operation
4. Long-term steroid therapy
5. Pre-operative estimated glomerular filtration rate < = 60 mls/min/1.73m2
6. Current congestive heart failure
7. Left ventricular (LV) ejection fraction < 30% (i.e. poor LV function)
8. Allergy to peanuts, eggs, egg products, soybeans or soy products
9. Already participating in another interventional clinical study
10. Prisoners
Women only:
11. Breast feeding
Recruitment start date
31/08/2018
Recruitment end date
31/01/2021
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Bristol Heart Institute
Marlborough Street
Bristol
BS2 8HW
United Kingdom
Trial participating centre
National Heart and Lung Institute
Hammersmith Hospital
Du Cane Road
London
W12 0HS
United Kingdom
Trial participating centre
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
Trial participating centre
Harefield Hopsital
Hill End Road
Harefield
UB9 6JH
United Kingdom
Trial participating centre
New Royal Infirmary of Edinburgh
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom
Trial participating centre
Wythenshawe Hospital
Southmoor Rd
Roundthorn Industrial Estate
Wythenshawe
M23 9LT
United Kingdom
Funders
Funder type
Government
Funder name
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 15/180/55
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal
IPD sharing statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Anonymised individual patient data (baseline, intervention, outcome data and adverse events) will be made available for secondary research, conditional on assurance from the secondary researcher that the proposed use of the data is compliant with the with the UK Policy Framework for Health and Social Care Research and MRC Policy on Data Preservation and Sharing regarding scientific quality, ethical requirements and value for money. Please contact Prof. Chris Rogers (prompt2-trial@bristol.ac.uk ) to discuss any data requests. Data will be made available after the study has been closed and the primary publication is out. It will be made available indefinitely. Only data from patients who have consented for their data to be shared with other researchers will be provided.
Intention to publish date
01/07/2022
Participant level data
Available on request
Basic results (scientific)
Publication list