An interventional study of Normothermic cardiopulmonary bypass and Hypothermic cardiopulmonary bypass in Coronary Artery Disease and Brain Injury, sponsored by Turku University Hospital. Not yet recruiting at 1 site in Finland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-05.
Sponsored by Turku University Hospital · Not applicable, Interventional, and Treatment
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recommendation is primarily based on two meta-analyses, but the underlying studies show methodological heterogeneity, outdated practices, and limited applicability to contemporary cardiac surgery.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.
In high-income countries, 36.7 coronary artery bypass grafting (CABG) procedures are performed per 100,000 population each year, translating to approximately 136,000 procedures in the European Union, and thereby underscoring the significant healthcare burden and importance of optimizing surgical outcomes. During cardiac surgery, cardiopulmonary bypass (CPB), a cornerstone of cardiac surgery, ensures extracorporeal perfusion to critical organs.
Historically, hypothermic CPB has been employed in the majority of cardiac operations and remains one of the most common methods for organ protection in routine cardiac surgery. The biological rationale for hypothermia is grounded in its multiple mechanisms of neuroprotection. Despite these findings, the superiority of hypothermic CPB over normothermic CPB in terms of neuroprotection remains uncertain.
In its 2024 guidelines, the European Association for Cardio-Thoracic Surgery recommends considering normothermia (defined as temperatures ≥ 35°C) to reduce the risk of postoperative neurocognitive dysfunction (Class II, Level A recommendation). Hypothermia, in this context, is defined as a core temperature below 35°C. The recommendation is based on two recent meta-analyses: Abbasciano et al. 2022 and Linassi et al. 2022. However, the 2024 recommendation is underpinned by evidence that remains limited in quality and relevance. The key studies included in these meta-analyses exhibit methodological inconsistencies and rely on outdated definitions and clinical practices, thereby limiting the generalizability and applicability of the findings to current cardiac surgical and anesthetic practice. Notably, the recommendation itself acknowledges the need for large randomized controlled trials to determine the optimal target temperature management (TTM) during cardiopulmonary bypass (CPB).
Previous studies using diffusion-weighted imaging (DWI) in magnetic resonance imaging (MRI) have revealed silent ischemic brain lesions, predominantly deep white matter lesions, in approximately 30% of patients following CABG. Furthermore, postoperative neurocognitive decline occurs in an average of 30.2% of CABG patients. However, earlier DWI and neurocognitive studies have not demonstrated statistically significant differences between normothermic and hypothermic CPB.
Diffusion tensor imaging (DTI) extends the capabilities of DWI and offers several advantages. Unlike DWI, which measures diffusion magnitude, DTI provides detailed quantitative insights into white matter architecture and allows for visualization and quantification of white matter tracts through tractography. Fractional anisotropy (FA), a key DTI parameter, quantifies the magnitude and directionality of water diffusion within white matter tracts. FA has shown independent prognostic value for neurological outcomes in patients with traumatic brain injury, subarachnoid hemorrhage, or cardiac arrest. Despite its potential, DTI has not yet been applied to CABG patients. This technique could significantly enhance our understanding of white matter microintegrity evolution and overall injury burden following CABG, insights necessary for optimizing TTM during CPB.
In addition to brain imaging with DTI, blood-based biomarkers such as glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), neuron-specific enolase (NSE), and total tau (T-tau) provide complementary tools for monitoring brain injury progression and improving prognostication of long-term neurological outcomes. Each biomarker are expressed in different cellular origins and exhibit distinct characteristics and temporal dynamics, potentially offering unique insights into the extent of brain injury post-CABG. However, their ability to independently or synergistically measure white and gray matter injury in combination with DTI parameters remains unexplored in CABG patients.
To optimize TTM during CPB, this study will investigate the neuroprotective effects of hypothermic (33-34 °C) and normothermic (36.5 °C) CPB by evaluating their impact on white matter injury, cerebral perfusion, and whole-brain neural networks using advanced MRI techniques.
The primary aim of this study is to evaluate whether mild hypothermic CPB offers superior neuroprotection compared to normothermic CPB. This will be assessed using brain DTI and blood-based biomarkers following CABG. Secondary objectives include evaluating the evolution of white matter architecture, the extent of global ischemic injury to white matter microintegrity, and the association between these factors, postoperative blood-based biomarker levels, and neurocognitive decline. In addition, an objective is to develop innovative and highly precise prognostic models by integrating advanced brain imaging technologies with comprehensive biomarker analysis. Ultimately, the overarching goal is to identify factors that can improve the treatment outcomes for patients undergoing CABG.
4,857 studies on the registry are indexed under Coronary Artery Disease; 890 are open to participants now.
This study's planned enrollment of 160 is above the median of 124 across 3,006 interventional studies indexed under Coronary Artery Disease.
Browse Coronary Artery Disease studies →Turku University Hospital is the lead sponsor of 287 studies on the registry; 67 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Intervention group: normothermic cardiopulmonary bypass with nasopharyngeal temperature of 36.5 ± 0.2°C
Procedure: Normothermic cardiopulmonary bypass
Control group: mild hypothermic cardiopulmonary bypass with nasopharyngeal temperature of 33 ± 0.2°C
Procedure: Hypothermic cardiopulmonary bypass
normothermic cardiopulmonary bypass with nasopharyngeal temperature of 36.5 ± 0.2°C
Also known as: 36.5 ± 0.2°C
mild hypothermic cardiopulmonary bypass with nasopharyngeal temperature of 33 ± 0.2°C
Also known as: 33 ± 0.2°C
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)
Time frame: Postoperative Day 6 +/- 1 day
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
The volume of hippocampus will be measured with voxel-based morphometry of magnetic resonance imaging at preoperative day 4 +/- 3 days and at postoperative day 6 +/- 1day.
Time frame: 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
Time frame: 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 ischemic injury in the hippocampus will be measured with magnetic resonance diffusion tensor imaging
Time frame: 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 ischemic injury in basal ganglia will be measured with the magnetic resonance diffusion tensor imaging
Time frame: 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
The global (i.e. the whole brain) ischemic white matter injury will be measured with fractional anisotropy and with radial, axial and mean diffusivity of the magnetic resonance diffusion tensor imaging. These parameters are always measured simultaneously and cannot be separated.
Time frame: Change of global ischemic white matter injury from preoperative day 4 +/- 3 to postoperative day 6 +/-1 day and to 3 months +/- 7 days
Change of global gray matter injury 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
The global (i.e. the whole brain) gray matter injury will be measured with mean diffusivity of diffusion tensor imaging
Time frame: Change of global gray matter injury from preoperative day 4 +/- 3 days to postoperative day 6 +/- 1 day and to 3 months +/- 7 days after operation
Difference of blood-based neuron specific enolase (NSE) between the control group and the intervention group
NSE is analyzed from a blood sample
Time frame: NSE is analysed immediately prior to anesthesia induction and at postoperative 24, 48 and at 72 hours
Difference of blood-based neurofilament light chain (NfL) between the control group and the intervention group
NfL is analyzed from a blood sample
Time frame: NfL is analyzed immediately prior to anesthesia induction and at postoperative 24, 48 and at 72 hours
Difference of blood-based glial fibrillary acidic protein (GFAP) between the control group and the intervention group
GFAP is analyzed from a blood sample
Time frame: GFAP is analyzed immediately prior to anesthesia induction and at postoperative 24, 48 and at 72 hours
Difference of blood-based total tau between the control group and the intervention group
total tau is analyzed from a blood sample
Time frame: total tau is analyzed immediately prior to anesthesia induction and at postoperative 24, 48 and at 72 hours
Difference of neurocognitive outcomes between the control group and the intervention group as assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB)
Time frame: CANTAB will be assessed at preoperative day 2 +/- 1 day and postoperatively at 3 and at 12 months
Difference of intraoperative Near-Infrared Spectroscopy NIRS values between the control and the intervention group during .
Time frame: NIRS will be measured intraoperatively
Difference in the need for vasoactive medication between the control group and the intervention group.
Vasoactive medication includes norepinephrine, epinephrine, vasopressin, levosimendan and nitroglycerin
Time frame: 96 hours after start of anesthesia induction
The need for antipyretic medication between the contorl group and the interventin group
Time frame: 96 hours after start of anesthesia induction
Blood lactate levels between the control group and the intervention group
Time frame: Lactate will be measured intraoperatively at 1-hour intervals and at intervals of 2 to 6 hours from the start to the end of postoperative intensive care
Difference of a quantity of blood products and hemostatic agents between the control and the intervention group
Time frame: 96 hours after start of anesthesia induction
Difference of the length of intensive care unit stay between the control group and the intervention group
Time frame: 96 hours after start of anesthesia induction
Plan to share: Yes — Primary endpoint
Supporting information: Clinical study report
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.
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