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

Not Applicable

Recruiting

• Conditions: Ischemic Heart Disease; Surgery-Complications; Cardiovascular Diseases; Valvular Heart Disease
• Interventions: Procedure: Normothermic Cardiopulmonary Bypass; Procedure: Hypothermic Cardiopulmonary Bypass

• Registration Number: NCT05996120
• Lead Sponsor: University of Leicester

Brief 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.

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 Timeline

• Study First Submitted: 2023-07-02
• Status Verified: 2023-08
• Study First Submitted QC: 2023-08-10
• Study First Posted: 2023-08-16
• Study Start: 2024-05-20
• Last Update Submitted: 2024-08-20
• Last Update Posted: 2024-08-21
• Primary Completion: 2024-11
• Study Completion: 2025-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normothermic Cardiopulmonary Bypass	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.
Hypothermic Cardiopulmonary Bypass	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.

Primary Outcome Measures

Name	Time	Method
Total number of participants recruited over a 6 month period	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	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

Secondary Outcome Measures

Name	Time	Method
Incidence of all adverse events	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.
Quality of life post-operation: Medical Outcomes Study Short-Form 36 (SF-36)	6 weeks	Quality of life questionnaire (SF-36) will administered before surgery and at 6-week follow up
Quality of life post-operation: European Quality of Life-5 Dimensions (EQ-5D)	6 weeks	Quality of life questionnaire (EQ-5D) will administered before surgery and at 6-week follow up
Incidence of 6-week composite endpoint of Major Adverse Cardiac and Cerebrovascular Events (MACCE)	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.
Frequency of post-discharge healthcare resource utilisation	6 weeks	Number of visits to general practitioner (GP) and/or hospital, either district general hospital or tertiary hospital, will be recorded via HealthBitⓇ.
Incidence of deep sternal wound infection, with or without treatment	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.
Critical care length of stay	6 weeks	Number of days a participant is admitted in cardiac critical care unit
Clinical Frailty Scale (CFS) post-operation	6 weeks	Clinical Frailty Scale will be recorded before surgery and at 6-week follow up
Post-operative length of stay	6 weeks	Number of days a participant is an in-patient after index operation
Quality of life post-operation: World Health Organisation Disability Assessment Schedule (WHODAS)	6 weeks	Quality of life questionnaire (WHODAS) will administered before surgery and at 6-week follow up

Trial Locations

Locations (11)

Glenfield Hospital, University Hospitals of Leicester NHS Trust; 🇬🇧 Leicester, Leicestershire, United Kingdom

Blackpool Victoria Hospital, Blackpool Teaching Hospitals NHS Foundation Trust; 🇬🇧 Blackpool, United Kingdom

Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust; 🇬🇧 Cottingham, United Kingdom

King's College Hospital, King's College Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom

Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom

Derriford Hospital, Plymouth University Hospitals NHS Trust; 🇬🇧 Plymouth, United Kingdom

Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust; 🇬🇧 Sheffield, United Kingdom

John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust; 🇬🇧 Oxford, United Kingdom

Harefield Hospital, Guy's and St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom

Golden Jubilee National Hospital, NHS Golden Jubilee; 🇬🇧 Glasgow, United Kingdom

University Hospitals Bristol and Weston NHS Foundation Trust; 🇬🇧 Bristol, United Kingdom