Study on Optimal Temperature During Cardiopulmonary Bypass (THERMIC-4) (THERMIC-4)

March 31, 2025 updated by: University of Leicester

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Gavin J Murphy, FRCS, MD, MBChB, BSc
  • Phone Number: 0116 258 3054
  • Email: gjm19@le.ac.uk

Study Contact Backup

Study Locations

  • United Kingdom
      • Blackpool, United Kingdom, FY3 8NR
        • Not yet recruiting
        • Blackpool Victoria Hospital, Blackpool Teaching Hospitals NHS Foundation Trust
        • Contact:
      • Bristol, United Kingdom, BS1 3NU
        • Recruiting
        • University Hospitals Bristol and Weston NHS Foundation Trust
        • Contact:
      • Cottingham, United Kingdom, HU16 5JQ
        • Recruiting
        • Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust
        • Contact:
      • Glasgow, United Kingdom, G81 4DY
        • Recruiting
        • Golden Jubilee National Hospital, NHS Golden Jubilee
      • London, United Kingdom, SW3 6NP
        • Not yet recruiting
        • Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust
        • Contact:
      • London, United Kingdom, UB9 6JH
        • Not yet recruiting
        • Harefield Hospital, Guy's and St Thomas' NHS Foundation Trust
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • King's College Hospital, King's College Hospital NHS Foundation Trust
        • Contact:
      • Oxford, United Kingdom, OX3 9DU
        • Recruiting
        • John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust
        • Contact:
      • Plymouth, United Kingdom, PL6 8DH
        • Recruiting
        • Derriford Hospital, Plymouth University Hospitals NHS Trust
        • Contact:
      • Sheffield, United Kingdom, S5 7AU
        • Recruiting
        • Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
        • Contact:
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE3 9QP
        • Recruiting
        • Glenfield Hospital, University Hospitals of Leicester NHS Trust
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA

Participants may enter the trial if all of the following apply

  1. Adult patients (≥ 18 years) scheduled for coronary artery bypass surgery and/or valve replacement/ repair, either in the elective or urgent setting.
  2. European System for Cardiac Operative Risk Evaluation (EuroSCORE) II of 2 or higher.
  3. Able to understand and communicate to provide informed consent.
  4. Able to read and understand the English language.

EXCLUSION CRITERIA

Participants may not enter the trial if any of the following apply:

  1. Patients undergoing coronary artery bypass surgery in combination with other procedures including cardiac or vascular procedures that require deep hypothermic arrest.
  2. Patients undergoing emergency or salvage surgery.
  3. Patients undergoing off-pump cardiac surgery.
  4. Patients who are participating in another interventional trial.
  5. Unable to provide informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Hypothermic Cardiopulmonary Bypass
Patients allocated to this arm will undergo standard care for coronary artery bypass grafting and/or valve surgery with mild hypothermia during CPB.
Procedure: Hypothermic Cardiopulmonary Bypass
Mild hypothermia (between 32 - 35 °C) during cardiopulmonary bypass
Active Comparator: Normothermic Cardiopulmonary Bypass
Patients allocated to this arm will undergo intervention care for coronary artery bypass grafting and/or valve surgery with normothermia hypothermia during CPB.
Procedure: Normothermic Cardiopulmonary Bypass
Normothermia (active maintenance of temperature between 36.5 °C to 37.5°C; no active cooling below 36.5 °C) during cardiopulmonary bypass

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months
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
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of 6-week composite endpoint of Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Time Frame: 6 weeks
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.
6 weeks
Incidence of deep sternal wound infection, with or without treatment
Time Frame: 6 weeks

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.
6 weeks
Incidence of all adverse events
Time Frame: 6 weeks
Composite of all reported adverse events. Examples of adverse events include: low cardiac output, suspected myocardial infarction, arrhythmias, infections, haemorrhage, and pulmonary embolus.
6 weeks
Critical care length of stay
Time Frame: 6 weeks
Number of days a participant is admitted in cardiac critical care unit
6 weeks
Post-operative length of stay
Time Frame: 6 weeks
Number of days a participant is an in-patient after index operation
6 weeks
Frequency of post-discharge healthcare resource utilisation
Time Frame: 6 weeks
Number of visits to general practitioner (GP) and/or hospital, either district general hospital or tertiary hospital, will be recorded via HealthBitⓇ.
6 weeks
Quality of life post-operation: Medical Outcomes Study Short-Form 36 (SF-36)
Time Frame: 6 weeks
Quality of life questionnaire (SF-36) will administered before surgery and at 6-week follow up
6 weeks
Quality of life post-operation: European Quality of Life-5 Dimensions (EQ-5D)
Time Frame: 6 weeks
Quality of life questionnaire (EQ-5D) will administered before surgery and at 6-week follow up
6 weeks
Quality of life post-operation: World Health Organisation Disability Assessment Schedule (WHODAS)
Time Frame: 6 weeks
Quality of life questionnaire (WHODAS) will administered before surgery and at 6-week follow up
6 weeks
Clinical Frailty Scale (CFS) post-operation
Time Frame: 6 weeks
Clinical Frailty Scale will be recorded before surgery and at 6-week follow up
6 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Data completeness
Time Frame: 6 months
Data recorded on HealthBitⓇ will be assessed for percentage of completion
6 months
Attrition rate
Time Frame: 6 months
For ascertainment of the primary outcome and for planning of future large-scale study
6 months
User satisfaction of ResearchApp
Time Frame: 6 months
Participants will be invited to complete optional survey on user satisfaction of ResearchApp
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Leicester

Collaborators

King's College Hospital NHS Trust
Sheffield Teaching Hospitals NHS Foundation Trust
University Hospitals, Leicester
Royal Brompton & Harefield NHS Foundation Trust
University Hospitals Bristol and Weston NHS Foundation Trust
Hull University Teaching Hospitals NHS Trust
Oxford University Hospitals NHS Trust
University Hospital Plymouth NHS Trust
NHS National Waiting Times Centre Board

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 20, 2024

Primary Completion (Estimated)

November 1, 2025

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

July 2, 2023

First Submitted That Met QC Criteria

August 10, 2023

First Posted (Actual)

August 16, 2023

Study Record Updates

Last Update Posted (Actual)

April 3, 2025

Last Update Submitted That Met QC Criteria

March 31, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0910
  • IRAS (Other Identifier: 348018)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Fully anonymised individual participant data can be made available on request for future studies with ethics approval.

IPD Sharing Time Frame

The investigators will retain the fully anonymised dataset indefinitely. The duration for which this will be shared will be determined on a case-by-case basis and defined in a Data Sharing Agreement.

IPD Sharing Access Criteria

Requests must be from studies with appropriate ethics approval in place.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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