Ischemic Heart DiseaseTHERMIC-4NCT05996120
Study on Optimal Temperature During Cardiopulmonary Bypass (THERMIC-4)
A study testing Hypothermic Cardiopulmonary Bypass and Normothermic Cardiopulmonary Bypass in people with Ischemic Heart Disease and Valvular Heart Disease, run by University of Leicester at 11 sites in United Kingdom.
Trial summary
In order to perform heart surgery, a machine called cardiopulmonary bypass (CPB), or more commonly known as a heart-lung machine, is used to maintain the circulation of oxygenated blood needed by the rest of the body and its organs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Heart Disease, Valvular Heart Disease, Cardiovascular Diseases
- What is being tested?
- Hypothermic Cardiopulmonary Bypass and Normothermic Cardiopulmonary Bypass
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 11 sitesUnited Kingdom
- Study dates
- 20 May 2024to Feb 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants may enter the trial if all of the following apply
- Adult patients (≥ 18 years) scheduled for coronary artery bypass surgery and/or valve replacement/ repair, either in the elective or urgent setting.
- European System for Cardiac Operative Risk Evaluation (EuroSCORE) II of 2 or higher.
- Able to understand and communicate to provide informed consent.
- Able to read and understand the English language.
Who cannot join
- Participants may not enter the trial if any of the following apply:
- Patients undergoing coronary artery bypass surgery in combination with other procedures including cardiac or vascular procedures that require deep hypothermic arrest.
- Patients undergoing emergency or salvage surgery.
- Patients undergoing off-pump cardiac surgery.
- Patients who are participating in another interventional trial.
- Unable to provide informed consent.
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Ann Cheng, MBChB, MSc contact
11 sites in 1 country
United Kingdom11 sites, 11 recruiting
- Not yet recruiting
Blackpool Victoria Hospital, Blackpool Teaching Hospitals NHS Foundation Trust
Blackpool, FY3 8NR
Marcus Taylor, marcus.taylor1@nhs.net
- Recruiting
University Hospitals Bristol and Weston NHS Foundation Trust
Bristol, BS1 3NU
Luke Rogers, ljrogers@doctors.org.uk
- Recruiting
Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust
Cottingham, HU16 5JQ
Mohamed Sherif, mohamed.sherif3@nhs.net
- Recruiting
Golden Jubilee National Hospital, NHS Golden Jubilee
Glasgow, G81 4DY
- Recruiting
Glenfield Hospital, University Hospitals of Leicester NHS Trust
Leicester, Leicestershire, LE3 9QP
Ann Cheng, ann.cheng1@nhs.net
- Recruiting
King's College Hospital, King's College Hospital NHS Foundation Trust
London, SE5 9RS
Naomi Watson, naomi.watson5@nhs.net
- Not yet recruiting
Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust
London, SW3 6NP
Ricky Vaja, r.vaja@rbht.nhs.uk
- Not yet recruiting
Harefield Hospital, Guy's and St Thomas' NHS Foundation Trust
London, UB9 6JH
- Recruiting
John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 9DU
Ali Ansaripour, ali.ansaripou@ouh.nhs.uk
- Recruiting
Derriford Hospital, Plymouth University Hospitals NHS Trust
Plymouth, PL6 8DH
Omar Zibdeh, o.zibdeh@nhs.net
- Recruiting
Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, S5 7AU
Olaniran Omodara, olaniran.omodara@nhs.net
About this study
Official title: Normothermic Versus Hypothermic Cardiopulmonary Bypass in Adult Cardiac Surgery: a Multicentre Feasibility Randomised Controlled Trial
In order to perform heart surgery, a machine called cardiopulmonary bypass (CPB), or more commonly known as a heart-lung machine, is used to maintain the circulation of oxygenated blood needed by the rest of the body and its organs.
Historically, when a patient is connected to CPB, their body is cooled below the normal body temperature. This is known as hypothermia. This is because scientific studies have previously shown that reduced body temperature lowers metabolism and therefore offers more protection to the brain and other organs due to the reduced oxygen requirement. The evidence supporting this practice, however, has been challenged throughout the history of cardiac surgery, with studies supporting that normothermia, or normal body temperature, is a safe alternative. Despite this, the practice of hypothermia has persisted. Published data from a survey of 139 cardiac surgeons in the United Kingdom showed that 84% still routinely employ hypothermic CPB during surgery.
To assess whether normothermic or hypothermic CPB is safer, a clinical trial requiring a large sample size and high recruitment rates will be required. Therefore, the investigators aim to assess firstly the feasibility of trial recruitment and allocation adherence in this study. 100 adults across 10 different cardiac surgery centres in the United Kingdom will be recruited to a multicentre feasibility randomised controlled trial comparing normothermia (active comparator) against hypothermia (control comparator) during cardiopulmonary bypass in cardiac surgery. This study will also test the ability of the Cardiothoracic Interdisciplinary Research Network (CIRN), a trainee-led research collaborative, to collect pilot data on Major Adverse Cardiac and Cerebrovascular Events (MACCE) using a regulation-approved electronic application HealthBitⓇ. Participants will also be asked to complete quality of life surveys. The results of this study will subsequently inform a large, adequately powered randomised controlled trial for optimal temperature management during CPB.
Read the detailed description
Primary Objective
To assess the feasibility of trial recruitment and delivery to target in the United Kingdom of a multicentre randomised controlled trial on normothermia versus hypothermia during cardiopulmonary bypass in adult cardiac surgery.
Secondary Objective
To assess the feasibility of conducting a multicentre randomized controlled trial (RCT) using a novel Good Clinical Practice (GCP) approved remote data capture as the primary trial database alongside analysis of routinely collected healthcare data.
To obtain pilot data, undertaken by the Cardiothoracic Interdisciplinary Research Network (CIRN), to inform a subsequent large, adequately powered RCT for optimal temperature management during CPB.
- Conditions
- Ischemic Heart Disease, Valvular Heart Disease, Cardiovascular Diseases, Surgery-Complications
- Being tested
- Hypothermic Cardiopulmonary Bypass, Normothermic Cardiopulmonary Bypass
- Keywords
- cardiopulmonary bypass, hypothermia, myocardial protection, neurologic protection
- Medical subject headings
- Myocardial Ischemia, Heart Valve Diseases, Cardiovascular Diseases, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypothermic Cardiopulmonary BypassProcedure or surgery
Mild hypothermia (between 32 - 35 °C) during cardiopulmonary bypass
Normothermic Cardiopulmonary BypassProcedure or surgery
Normothermia (active maintenance of temperature between 36.5 °C to 37.5°C; no active cooling below 36.5 °C) during cardiopulmonary bypass
| Study group | Role | What they receive |
|---|---|---|
| Hypothermic Cardiopulmonary Bypass | Active comparator | Patients allocated to this arm will undergo standard care for coronary artery bypass grafting and/or valve surgery with mild hypothermia during CPB. Receives: Procedure: Hypothermic Cardiopulmonary Bypass |
| Normothermic Cardiopulmonary Bypass | Active comparator | Patients allocated to this arm will undergo intervention care for coronary artery bypass grafting and/or valve surgery with normothermia hypothermia during CPB. Receives: Procedure: Normothermic Cardiopulmonary Bypass |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total number of participants recruited over a 6 month period
The target recruitment rate is 1 participant per week per centre. The feasibility trial will be considered positive if 80% of target met, together with outcome 2.
Measured: 6 months
Adherence rate to allocation
The feasibility trial will be considered positive if 74%* of target adherence to trial allocation is met, together with outcome 1.
*74% is derived from 80% of target adherence of 92% as per Warm Heart Study
Measured: 6 months
Secondary outcomes (10)
Incidence of 6-week composite endpoint of Major Adverse Cardiac and Cerebrovascular Events (MACCE)
MACCE is defined as any post-operative death, stroke, new intra-aortic balloon pump insertion, new renal replacement therapy, re-operation and major bleeding in this feasibility trial.
Measured: 6 weeks
Incidence of deep sternal wound infection, with or without treatment
Deep sternal wound infection is defined with at least one of the following criteria:
(I) an organism is isolated from culture of mediastinal tissue or fluid (II) evidence of mediastinitis seen intraoperatively (III) presence of chest pain, sternal instability, or fever (> 38 °C), and purulent drainage from the mediastinum or isolation of organism present in a blood culture or from the mediastinal area.
Measured: 6 weeks
Incidence of all adverse events
Composite of all reported adverse events. Examples of adverse events include: low cardiac output, suspected myocardial infarction, arrhythmias, infections, haemorrhage, and pulmonary embolus.
Measured: 6 weeks
Critical care length of stay
Number of days a participant is admitted in cardiac critical care unit
Measured: 6 weeks
Post-operative length of stay
Number of days a participant is an in-patient after index operation
Measured: 6 weeks
Frequency of post-discharge healthcare resource utilisation
Number of visits to general practitioner (GP) and/or hospital, either district general hospital or tertiary hospital, will be recorded via HealthBitⓇ.
Measured: 6 weeks
Quality of life post-operation: Medical Outcomes Study Short-Form 36 (SF-36)
Quality of life questionnaire (SF-36) will administered before surgery and at 6-week follow up
Measured: 6 weeks
Quality of life post-operation: European Quality of Life-5 Dimensions (EQ-5D)
Quality of life questionnaire (EQ-5D) will administered before surgery and at 6-week follow up
Measured: 6 weeks
Quality of life post-operation: World Health Organisation Disability Assessment Schedule (WHODAS)
Quality of life questionnaire (WHODAS) will administered before surgery and at 6-week follow up
Measured: 6 weeks
Clinical Frailty Scale (CFS) post-operation
Clinical Frailty Scale will be recorded before surgery and at 6-week follow up
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2023
- Study start20 May 2024
- Primary completionNov 2025 (estimated)
- Study completionFeb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic Heart DiseaseStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel group, open label, statistician blinded, multicentre, randomised controlled feasibility trial.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Collaborators
- NHS National Waiting Times Centre Board, Sheffield Teaching Hospitals NHS Foundation Trust, Oxford University Hospitals NHS Trust, Hull University Teaching Hospitals NHS Trust, University Hospitals Bristol and Weston NHS Foundation Trust, University Hospitals, Leicester, Royal Brompton & Harefield NHS Foundation Trust, King's College Hospital NHS Trust, University Hospital Plymouth NHS Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05996120
- Sponsor's protocol ID
- 0910
- Other IDs
- IRAS
- Acronym
- THERMIC-4
- Status last verified
- Mar 2025
- First submitted
- 2 Jul 2023
- Last updated
- 3 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Fully anonymised individual participant data can be made available on request for future studies with ethics approval.
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Normothermic Versus Hypothermic Cardiopulmonary Bypass in Adult Cardiac Surgery: a Multicentre Feasibility Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT05996120
- Acronym / sponsor ID
- THERMIC-4 / 0910
- Conditions
- Ischemic Heart Disease, Valvular Heart Disease, Cardiovascular Diseases, Surgery-Complications
- Keywords
- cardiopulmonary bypass, hypothermia, myocardial protection, neurologic protection
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Collaborators
- NHS National Waiting Times Centre Board, Sheffield Teaching Hospitals NHS Foundation Trust, Oxford University Hospitals NHS Trust, Hull University Teaching Hospitals NHS Trust, University Hospitals Bristol and Weston NHS Foundation Trust, University Hospitals, Leicester, Royal Brompton & Harefield NHS Foundation Trust, King's College Hospital NHS Trust, University Hospital Plymouth NHS Trust
- Study start
- 20 May 2024 (actual)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 16 Aug 2023 (actual)
- 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.
In order to perform heart surgery, a machine called cardiopulmonary bypass (CPB), or more commonly known as a heart-lung machine, is used to maintain the circulation of oxygenated blood needed by the rest of the body and its organs.
Historically, when a patient is connected to CPB, their body is cooled below the normal body temperature. This is known as hypothermia. This is because scientific studies have previously shown that reduced body temperature lowers metabolism and therefore offers more protection to the brain and other organs due to the reduced oxygen requirement. The evidence supporting this practice, however, has been challenged throughout the history of cardiac surgery, with studies supporting that normothermia, or normal body temperature, is a safe alternative. Despite this, the practice of hypothermia has persisted. Published data from a survey of 139 cardiac surgeons in the United Kingdom showed that 84% still routinely employ hypothermic CPB during surgery.
To assess whether normothermic or hypothermic CPB is safer, a clinical trial requiring a large sample size and high recruitment rates will be required. Therefore, the investigators aim to assess firstly the feasibility of trial recruitment and allocation adherence in this study. 100 adults across 10 different cardiac surgery centres in the United Kingdom will be recruited to a multicentre feasibility randomised controlled trial comparing normothermia (active comparator) against hypothermia (control comparator) during cardiopulmonary bypass in cardiac surgery. This study will also test the ability of the Cardiothoracic Interdisciplinary Research Network (CIRN), a trainee-led research collaborative, to collect pilot data on Major Adverse Cardiac and Cerebrovascular Events (MACCE) using a regulation-approved electronic application HealthBitⓇ. Participants will also be asked to complete quality of life surveys. The results of this study will subsequently inform a large, adequately powered randomised controlled trial for optimal temperature management during CPB.
Detailed description
Primary Objective
To assess the feasibility of trial recruitment and delivery to target in the United Kingdom of a multicentre randomised controlled trial on normothermia versus hypothermia during cardiopulmonary bypass in adult cardiac surgery.
Secondary Objective
To assess the feasibility of conducting a multicentre randomized controlled trial (RCT) using a novel Good Clinical Practice (GCP) approved remote data capture as the primary trial database alongside analysis of routinely collected healthcare data.
To obtain pilot data, undertaken by the Cardiothoracic Interdisciplinary Research Network (CIRN), to inform a subsequent large, adequately powered RCT for optimal temperature management during CPB.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Parallel group, open label, statistician blinded, multicentre, randomised controlled feasibility trial.
| Arm | Type | Receives |
|---|---|---|
| Hypothermic Cardiopulmonary Bypass | Active comparator | Procedure: Hypothermic Cardiopulmonary BypassPatients allocated to this arm will undergo standard care for coronary artery bypass grafting and/or valve surgery with mild hypothermia during CPB. |
| Normothermic Cardiopulmonary Bypass | Active comparator | Procedure: Normothermic Cardiopulmonary BypassPatients allocated to this arm will undergo intervention care for coronary artery bypass grafting and/or valve surgery with normothermia hypothermia during CPB. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Participants may enter the trial if all of the following apply
- Adult patients (≥ 18 years) scheduled for coronary artery bypass surgery and/or valve replacement/ repair, either in the elective or urgent setting.
- European System for Cardiac Operative Risk Evaluation (EuroSCORE) II of 2 or higher.
- Able to understand and communicate to provide informed consent.
- Able to read and understand the English language.
Key exclusion criteria (6 listed)
- Patients undergoing coronary artery bypass surgery in combination with other procedures including cardiac or vascular procedures that require deep hypothermic arrest.
- Patients undergoing emergency or salvage surgery.
- Patients undergoing off-pump cardiac surgery.
- Patients who are participating in another interventional trial.
- Unable to provide informed consent.
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 |
|---|---|---|
| Hypothermic Cardiopulmonary BypassMild hypothermia (between 32 - 35 °C) during cardiopulmonary bypass | Procedure or surgery | Hypothermic Cardiopulmonary Bypass |
| Normothermic Cardiopulmonary BypassNormothermia (active maintenance of temperature between 36.5 °C to 37.5°C; no active cooling below 36.5 °C) during cardiopulmonary bypass | Procedure or surgery | Normothermic Cardiopulmonary Bypass |
Primary outcome
Total number of participants recruited over a 6 month period
Time frame: 6 months
The target recruitment rate is 1 participant per week per centre. The feasibility trial will be considered positive if 80% of target met, together with outcome 2.
Adherence rate to allocation
Time frame: 6 months
The feasibility trial will be considered positive if 74%* of target adherence to trial allocation is met, together with outcome 1. *74% is derived from 80% of target adherence of 92% as per Warm Heart Study
10 secondary outcomes
Incidence of 6-week composite endpoint of Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Time frame: 6 weeks
Incidence of deep sternal wound infection, with or without treatment
Time frame: 6 weeks
Incidence of all adverse events
Time frame: 6 weeks
Critical care length of stay
Time frame: 6 weeks
Post-operative length of stay
Time frame: 6 weeks
Frequency of post-discharge healthcare resource utilisation
Time frame: 6 weeks
Quality of life post-operation: Medical Outcomes Study Short-Form 36 (SF-36)
Time frame: 6 weeks
Quality of life post-operation: European Quality of Life-5 Dimensions (EQ-5D)
Time frame: 6 weeks
Quality of life post-operation: World Health Organisation Disability Assessment Schedule (WHODAS)
Time frame: 6 weeks
Clinical Frailty Scale (CFS) post-operation
Time frame: 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2025.
- Individual participant dataSharing planned: Yes. Fully anonymised individual participant data can be made available on request for future studies with ethics approval.
Related trials for Ischemic Heart Disease
Recruiting
Heart@Home Safety and Efficacy of Hospital-at-Home Care Versus Standard Hospitalization in Cardiac Patients
Myocardial Infarction, Myocarditis Acute
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
Not yet recruiting
ADVA ACE Coronary Stent System in Coronary Artery Disease Patients (ADVANCE)
Coronary Artery Disease, De Novo Stenosis Lesion
Not yet recruiting
Out-Patient Proactive Observation With Wearable-Assisted Tracking for Cardiovascular Health Management
Chronic Coronary Syndrome
RecruitingObservational study
Mechanical Dyssynchrony and Microvascular Dysfunction by SPECT
Myocardial Blood Flow Reserve, Mechanical Dyssynchrony
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.
Ann Cheng, MBChB, MSc contact
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hypothermic Cardiopulmonary Bypass and Normothermic Cardiopulmonary Bypass in people with Ischemic Heart Disease and Valvular Heart Disease, run by University of Leicester at 11 sites 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 5 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 3 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gavin J Murphy, FRCS, MD, MBChB, BSc (0116 258 3054, gjm19@le.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total number of participants recruited over a 6 month period (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Apr 2025.