Neuroprotective Effect of Mild Hypothermia Versus Normothermia During Cardiopulmonary Bypass of Coronary Artery Surgery

NCT07316868 | Not Yet Recruiting DMC

• 1 other identifier: VARHA/4272/13.02.02/2025
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

In high-income countries, coronary artery bypass grafting (CABG) remains a common procedure, with approximately 36.7 operations per 100,000 inhabitants annually, corresponding to about 136,000 procedures in the European Union. This highlights the substantial healthcare burden and the need to optimize surgical outcomes. Cardiopulmonary bypass (CPB) is a fundamental component of cardiac surgery, ensuring extracorporeal perfusion of vital organs. Hypothermic CPB has historically been widely used for organ protection due to its presumed neuroprotective mechanisms. However, evidence demonstrating its superiority over normothermic CPB remains inconclusive. In its 2024 guidelines, the European Association for Cardio-Thoracic Surgery recommends considering normothermia (≥35 °C) to reduce postoperative neurocognitive dysfunction (Class II, Level A). This recommendation is primarily based on two meta-analyses, but the underlying studies show methodological heterogeneity, outdated practices, and limited applicability to contemporary cardiac surgery. Importantly, the guidelines acknowledge the need for large randomized controlled trials to define optimal target temperature management (TTM) during CPB. Previous diffusion-weighted MRI studies have demonstrated silent ischemic brain lesions in approximately 30% of CABG patients, with postoperative neurocognitive decline occurring in a similar proportion. However, no significant differences have been shown between normothermic and hypothermic CPB. Diffusion tensor imaging (DTI) extends conventional diffusion imaging by enabling detailed assessment of white matter microstructure and tractography. Fractional anisotropy (FA), a key DTI metric, has demonstrated prognostic value in various neurological conditions but has not yet been applied in CABG patients. Blood-based biomarkers, including glial fibrillary acidic protein, neurofilament light chain, neuron-specific enolase, and total tau, offer complementary insights into brain injury but have not been studied in combination with DTI in this population. This study will compare mild hypothermic (33-34 °C) and normothermic (36.5 °C) CPB to evaluate their neuroprotective effects using advanced MRI techniques and blood-based biomarkers. The primary aim is to determine whether mild hypothermia provides superior neuroprotection following CABG. Secondary objectives include assessing white matter injury evolution, global ischemic burden, associations with biomarkers and neurocognitive decline, and developing integrated prognostic models to improve outcomes in CABG patients.

Conditions

Coronary Artery Disease; Brain Injury

Keywords

hypothermia; normothermia; cardiopulmonary bypass; coronary artery bypass grafting; diffusion tensor imaging; neuroprotection; biomarkers

Outcome Measures

Primary Outcomes (1)

• Global fractional anisotropy of brain white matter of diffusion tensor imaging (DTI)

  Fractional anisotropy measures white matter microintegrity. It is assessed with brain magnetic resonance diffusion tenson imaging (DTI)

  Postoperative Day 6 +/- 1 day

Secondary Outcomes (17)

• Change in hippocampal volume in milliliters (ml) from preoperative day 4 (+/- 3 days) to postoperative day 6 (+/-1 day) between the control and the intervention group

  Change of hippocampal volume between preoperative day 4 +/- 3 days and postoperative day 6 +/- 1day

• Number of participants with treatment related adverse events as assessed by CTCAE v 4.0

  From enrollment to the end of follow-up at 1 year

• Change in hippocampal ischemic injury from preoperative day 4 +/- 3 days to postoperative day 6 +/- 1 day between the control group and the intervention group.

  The change of hippocampal ischemic injury from the preoperative day 4 +/-3 days to postoperative day 6 +/- 1 day

• Change in ischemic injury of basal ganglia from preoperative day 4 +/- 3 days to postoperative day 6+/- 1 day between the control group and the intervention group

  The change of ischemic injury in basal ganglia from the ppreoperative day 4 +/- 3 days to postoperative day 6 +/- 1 day

• Change of global white matter injury as assessed with diffusion tensor imaging between the control group and the intervention group from preoperative day 4 +/- 3 days to postoperative day 6 +/- 1 day and to 3 months +/- 7 days

  Change of global ischemic white matter injury from preoperative day 4 +/- 3 to postoperative day 6 +/-1 day and to 3 months +/- 7 days

Study Arms (2)

Intervention group

ACTIVE COMPARATOR

Intervention group: normothermic cardiopulmonary bypass with nasopharyngeal temperature of 36.5 ± 0.2°C

Procedure: Normothermic cardiopulmonary bypass

Control group

ACTIVE COMPARATOR

Control group: mild hypothermic cardiopulmonary bypass with nasopharyngeal temperature of 33 ± 0.2°C

Procedure: Hypothermic cardiopulmonary bypass

Interventions

Normothermic cardiopulmonary bypass PROCEDURE

normothermic cardiopulmonary bypass with nasopharyngeal temperature of 36.5 ± 0.2°C

Also known as: 36.5 ± 0.2°C

Intervention group

Hypothermic cardiopulmonary bypass PROCEDURE

mild hypothermic cardiopulmonary bypass with nasopharyngeal temperature of 33 ± 0.2°C

Also known as: 33 ± 0.2°C

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent obtained
• Age of \>18 years
• Undergoing elective or subacute coronary artery bypass grafting

You may not qualify if:

• An emergency case
• A history of stroke
• A history of intracranial bleeding
• A history of transient ischemic attack (TIA)
• A history of neurodegenerative diseases such as Alzheimer's, multiple sclerosis
• The subject is known to have a clinically significant laboratory abnormality, medical condition (such as decompensated liver disease or severe chronic obstructive pulmonary disease), or social circumstance that, in the investigator's opinion, makes it inappropriate for the subject to participate in this clinical trial.
• Presence of implants or foreign bodies which are not known to be MRI safe

Sponsors & Collaborators

• Turku University Hospital: lead

Study Sites (1)

Turku University Hospital

Turku, FIN-20521, Finland

Location

MeSH Terms

Conditions

Coronary Artery Disease; Brain Injuries; Hypothermia

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Timo Laitio, MD, PhD

  Turku University Hospital, Wellbeing Services County of Southwest Finland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timo Laitio, M.D., PhD

CONTACT

+358504731639; timo.laitio@varha.fi

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a single-blinded randomized clinical trial

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: January 5, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: from January 1, 2027 to December 31, 2029
• Access Criteria: The data of this study will be available to investigators whose proposed use of the data has been approved by an independent review committee. Individual participant data that underlie the results reported in this Article will be shared (text, tables, figures, and appendices), after de-identification, along with the study protocol. These data will be available 6 months after the Article's publication and will be available for 12 months from publication. Data can be used for individual participant data meta-analysis. Requests and proposals should be directed to timo.laitio@elisanet.fi. To gain access, data requestors will need to sign a data access agreement.

Locations

FI (1)