Propofol in cardiac surgery: ProMPT-2
| ISRCTN | ISRCTN15255199 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15255199 |
| EudraCT/CTIS number | 2018-000169-35 |
| Secondary identifying numbers | CPMS 37464 |
- Submission date
- 11/03/2019
- Registration date
- 26/03/2019
- Last edited
- 27/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
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 March 2024
Who is funding the study?
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC)
Who is the main contact?
Beth Fitzgerald, Prompt2-trial@bristol.ac.uk
Contact information
Public
Bristol Trials Centre
University of Bristol
1-5 Whiteladies Road
Bristol
BS8 1NU
United Kingdom
| Prompt2-trial@bristol.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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 |
| Study acronym | ProMPT 2 |
| Study objectives | Adding propofol to the cardioplegic solution used during cardiac surgery reduces organ damage |
| Ethics approval(s) | 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; +44 (0)207 104 8059), ref: 18/SC/0472 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 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 | Current secondary outcome measures as of 06/06/2023: 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. Length of intensive care unit (ICU) stay 6. Length of postoperative hospital stay 7. 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 8. QoL measured using the Coronary Revascularisation Outcome Questionnaire (CROQ) and the EQ-5D-5L questionnaire at baseline, 3 months and 12 months _____ Previous secondary outcome measures as of 27/05/2022: 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 (Bristol cohort only) 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 (Bristol cohort only) 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 _____ Previous 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 study start date | 01/12/2017 |
| Completion date | 31/03/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 240; UK Sample Size: 240 |
| Total final enrolment | 240 |
| Key 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 |
| Key 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. Breastfeeding |
| Date of first enrolment | 31/08/2018 |
| Date of final enrolment | 07/11/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Bristol
BS2 8HW
United Kingdom
Du Cane Road
London
W12 0HS
United Kingdom
Leicester
LE3 9QP
United Kingdom
Harefield
UB9 6JH
United Kingdom
Roundthorn Industrial Estate
Wythenshawe
M23 9LT
United Kingdom
Bath
BA1 3NG
United Kingdom
Taunton
TA1 5DA
United Kingdom
Sponsor information
University/education
Beacon House
Queens Road
Bristol
BS8 1TH
England
United Kingdom
"ROR" |
https://ror.org/0524sp257 |
|---|
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 30/04/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 16/02/2023 | 17/02/2023 | Yes | No | |
| HRA research summary | 26/07/2023 | No | No | ||
| Statistical Analysis Plan | 29/02/2024 | 01/03/2024 | Yes | No |
Editorial Notes
27/03/2025: The intention to publish date was changed from 31/05/2024 to 30/04/2025.
01/03/2024: Publication reference added. The intention to publish date was changed from 30/04/2024 to 31/05/2024.
18/12/2023: The study contact was updated.
03/11/2023: The following changes were made to the trial record:
1. The overall end date was changed from 30/11/2023 to 31/03/2024.
2. The intention to publish date was changed from 31/01/2024 to 30/04/2024.
3. The plain English summary was updated to reflect these changes.
06/06/2023: The following changes were made to the trial record:
1. The overall end date was changed from 30/09/2023 to 30/11/2023.
2. The secondary outcome measures were changed.
3. The total final enrolment was added.
4. The recruitment end date was changed from 30/09/2022 to 07/11/2022.
5. The plain English summary was updated to reflect these changes.
17/02/2023: Publication reference added.
27/05/2022: The following changes have been made:
1. The public contact has been changed.
2. The secondary outcome measures have been changed.
3. The intention to publish date has been changed from 01/07/2022 to 31/01/2024.
4. Royal United Hospitals Bath and Musgrove Park Hospital have been added to the trial participating centres.
31/03/2022: The following changes have been made:
1. The recruitment end date has been changed from 31/01/2021 to 30/09/2022.
2. The overall trial end date has been changed from 01/01/2022 to 30/09/2023 and the plain English summary has been updated to reflect this change.
3. The acronym has been added.
26/04/2021: New Royal Infirmary of Edinburgh has been removed from the trial participating centres.
17/06/2020: The public contact details have been made publicly visible.
20/05/2020: The following changes have been made:
1. The intervention phase has been changed from "Not applicable" to "Phase II".
2. The participant exclusion criteria have been updated.
3. The trial participating centres "Glenfield Hospital", "Harefield Hospital", "New Royal Infirmary of Edinburgh" and "Wythenshawe Hospital" have been added.
4. The study manager listed in the plain English summary has been updated from "Clinical Trials and Evaluation Unit" to "Bristol Trials Centre".
5. The trial contact has been updated.
6. The plain English summary has been updated to reflect the changes above.
11/04/2019: The condition has been changed from "Specialty: Cardiovascular Disease, Primary sub-specialty: Cardiac Surgery; Health Category: Cardiovascular; Disease/Condition: Ischaemic heart diseases" to "Reperfusion injury of the heart following coronary artery bypass grafting (CABG) surgery" following a request from the NIHR.
