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

Cardiovascular Diseases Clinical Trial

— THERMIC-4  

Official title:

Normothermic Versus Hypothermic Cardiopulmonary Bypass in Adult Cardiac Surgery: a Multicentre Feasibility Randomised Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05996120
• Other study ID #: 0910
• Secondary ID: IRAS
• Status: Recruiting
• Phase: N/A
• Start date: May 20, 2024
• Est. completion date: February 2025

Study information

• Verified date: June 2023
• Source: University of Leicester
• Contact: Gavin J Murphy, FRCS, MD, MBChB, BSc
• Phone: 0116 258 3054
• Email: gjm19[@]le.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Artery Disease
• Heart Diseases
• Heart Valve Diseases
• Ischemic Heart Disease
• Myocardial Ischemia
• Valvular Heart Disease

Intervention

Procedure:
• Hypothermic Cardiopulmonary Bypass
Mild hypothermia (between 32 - 35 °C) during cardiopulmonary bypass
• 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

Locations

Country	Name	City	State
United Kingdom	University Hospitals Bristol and Weston NHS Foundation Trust	Bristol
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester	Leicestershire

Sponsors (9)

Lead Sponsor	Collaborator
University of Leicester	Blackpool Teaching Hospitals NHS Foundation Trust, Guy's and St Thomas' NHS Foundation Trust, Hull University Teaching Hospitals NHS Trust, NHS National Waiting Times Centre Board, Oxford University Hospitals NHS Trust, Sheffield Teaching Hospitals NHS Foundation Trust, University Hospitals Bristol and Weston NHS Foundation Trust, University Hospitals, Leicester

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Data completeness	Data recorded on HealthBit? will be assessed for percentage of completion	6 months
Other	Attrition rate	For ascertainment of the primary outcome and for planning of future large-scale study	6 months
Other	User satisfaction of ResearchApp	Participants will be invited to complete optional survey on user satisfaction of ResearchApp	6 months
Primary	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.	6 months
Primary	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	6 months
Secondary	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.	6 weeks
Secondary	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.	6 weeks
Secondary	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.	6 weeks
Secondary	Critical care length of stay	Number of days a participant is admitted in cardiac critical care unit	6 weeks
Secondary	Post-operative length of stay	Number of days a participant is an in-patient after index operation	6 weeks
Secondary	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?.	6 weeks
Secondary	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	6 weeks
Secondary	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	6 weeks
Secondary	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	6 weeks
Secondary	Clinical Frailty Scale (CFS) post-operation	Clinical Frailty Scale will be recorded before surgery and at 6-week follow up	6 weeks