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BiomarkersNCT07231731

Dynamics of microRNA Expression and Systemic Inflammatory Response in POCD After Cardiac Surgery

An observational study of Biomarkers and Coronary Artery Bypass Surgery, run by Osijek University Hospital at 1 site in Croatia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Postoperative cognitive decline (POCD) is one of the most common complications after cardiac surgery. It is characterized by impaired memory, attention, and executive functions and can have long-term consequences. Read more about this study

Who is it for?
Ages 65 to 80 years
How many people
48 participants
Where
1 siteCroatia
Study dates
31 May 2022to 26 Oct 2023
How long will I take part?
7 Days
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 to 80 years
  • All sexes
  • No healthy volunteers
  • Older adult

Study population: Patients undergoing coronary artery bypass grafting surgery at the Department of Cardiac and Thoracic Surgery of the Clinic for Surgery, Clinical Hospital Center Osijek.

Who may be able to join

  • patients undergoing coronary artery bypass graft surgery to treat coronary artery disease
  • two or more coronary bypass surgery with the use of extracorporeal circulation
  • patients between the ages of 65 and 80
  • patients according to the classification of the American Society of Anesthesiologists (ASA) classified in groups III and IV
  • patients who agreed to participate in the research and signed an informed consent

Who cannot join

  • patients with communication difficulties (severe visual, hearing and speech impairment)
  • illiterate patients
  • patients with a history of dementia, schizophrenia, Parkinson's disease, Alzheimer's disease, alcoholism
  • patients with previously known liver failure of any grade according to the Child-Pough classification
  • patients with previously known renal failure greater than grade 2
  • patients taking immunosuppressive, corticosteroid and anticholinergic therapy
Show all 9Show fewer
  • intraoperatively used cell-saver and/or hemofilter
  • patients in whom the planned procedure is not performed
  • patients in whom it is not possible to assess cognitive functions postoperatively (patients sedated due to intra- or postoperative surgical complications)

Trial locations and contacts

1 site in 1 country.

Croatia1 site
  • University Hospital Osijek

    Osijek, 31000

Other trials in Croatia

About this study

Official title: Association of MicroRNA-151-5p Expression With Systemic Inflammatory Response and Cognitive Status in Patients After Coronary Artery Bypass Surgery (MiRNACOG)

Postoperative cognitive decline (POCD) is one of the most common complications after cardiac surgery. It is characterized by impaired memory, attention, and executive functions and can have long-term consequences. The goal of this observational study was to investigate the mechanisms of cognitive decline after cardiac surgery and potential biomarkers that could aid in the diagnosis, prevention, and treatment of POCD. The investigators focused on the role of microRNAs (miRNAs) and systemic inflammatory response to surgery, extracorporeal circulation, and anesthesia as potential factors involved in the development of the neuroinflammatory response and subsequent POCD. The main question this study aims to answer is whether perioperative miRNA 151-5p expression is associated with POCD after surgery. The second aim is to examine the association between miRNA-151-5p and systemic inflammation. The investigators measured circulating miRNA-151-5p levels and plasma levels of inflammatory biomarkers in patients undergoing surgical myocardial revascularization. To assess cognitive function, participants completed the Montreal Cognitive Assessment (MoCA Test). Changes in the measured values of miRNA-151-5p expression and inflammatory markers, as well as changes in cognitive status after surgery, were assessed in relation to the preoperative state.

Read the detailed description

Surgical myocardial revascularization is a procedure used in patients with ischemic heart disease to bypass atherosclerotic narrowings or blockages of the coronary arteries using an arterial or venous graft (Coronary Artery Bypass Grafting - CABG). One of the most common complications after cardiac surgery is postoperative cognitive decline (POCD). It is characterized by impaired memory, attention, and executive functions and can have long-term consequences, such as delayed physical therapy and mobilization, prolonged stay in the intensive care unit and hospital, more frequent discharge to nursing homes, reduced quality of life, and increased mortality.

The causes of POCD are multifactorial. The systemic inflammatory response to surgery, extracorporeal circulation, and anesthesia is considered a factor in the development of the neuroinflammatory response and subsequent POCD. Neuroinflammation can cause dysfunction or death of brain cells and damage to the blood-brain barrier, leading to an increase in the level of biochemical markers of brain injury in the blood. Studies indicate that numerous microRNAs (miRNAs) play a role in controlling the inflammatory response. MiRNAs are small, endogenous, non-coding RNA molecules, typically 18-25 nucleotides long, that regulate gene expression at the post-transcriptional level. They are central mediators of cellular proliferation, differentiation, and apoptosis. MiRNA levels in tissues and peripheral blood are similar, and circulating miRNAs are stable and suitable for measurement. Specific miRNAs (miRNA 151-5p, 505, 499, 625, and others) may be potential early biomarkers of brain damage after a mild traumatic brain injury. Anesthesia and surgery also, through complex mechanisms, can cause changes in brain cells that can lead to the release of specific miRNAs, and these miRNAs can be detected in blood and various biological fluids.

Hypothesis: Higher levels of perioperative miRNA-151-5p expression are associated with the systemic inflammatory response and with the development of POCD.

Aim of this study is:

  1. To investigate the association between miRNA-151-5p expression levels and biochemical parameters of systemic inflammation, as well as the association of both with cognitive status in patient undergoing CABG surgery.
  2. To investigate the association between patients' demographic and clinical characteristics and miRNA-151-5p expression levels, the level of biochemical parameters of systemic inflammation, and patients' cognitive status.

Research plan:

The research was carried out at the Clinical Hospital Centre Osijek. Respecting the inclusion and exclusion criteria for participation in the study, the research included patients aged 65 to 80 years who, according to the American Society of Anesthesiologists (ASA) classification, are classified into groups III and IV, and who are undergoing CABG surgery with the use of extracorporeal circulation. Surgeries were performed according to the standard protocol for balanced anesthesia, cardiac surgery, and extracorporeal circulation. All participants underwent the same anesthetic procedure and anesthesia based on midazolam, propofol, sufentanyl, rocuronium and sevoflurane. The depth of anesthesia was monitored using Patient State Index (PSI). All surgeries were performed using extracorporeal circulation with the maintenance of normothermia (36 °C).

Blood samples for determination of levels of cholinesterase, interleukin-6, protein S100B, miRNA-151-5p expression and routine laboratory parameters (complete blood count, levels of troponin I, C-reactive protein, procalcitonin, glucose, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, total bilirubin, albumin, electrolytes, lactate, coagulation tests, and arterial blood gas analysis) were taken at three time points: before surgery prior to induction of anesthesia, immediately after the procedure upon admission to the intensive care unit, and 48 hours after the surgical procedure.

Cognitive function testing was performed the day before surgery and postoperatively, once daily every day until the 6th postoperative day. The investigators used a validated scoring scale for assessing cognitive functions, the Montreal Cognitive Assessment - MoCA Test. Demographic and clinical data were recorded for all subjects. Subjects were followed up 7 days.

Keywords
Anesthesia, General, Blood-Brain Barrier, Cardiac Surgical Procedures, Cardiopulmonary Bypass, Cholinesterases, Cognitive Disorders, Cognitive Dysfunction, Coronary Artery Bypass, Coronary Artery Disease, Critical Care, Extracorporeal Circulation, Gene Expression, Inflammation, Interleukins, Mental Disorders, Myocardial Revascularization, Nervous System Diseases, Neurocognitive Disorders, Neuroinflammatory Diseases, Neuropsychological Tests
Medical subject headings
Postoperative Cognitive Complications, Systemic Inflammatory Response Syndrome, Cognitive Dysfunction, Coronary Artery Disease, Inflammation, Mental Disorders, Nervous System Diseases, Neurocognitive Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07231731
Study groupRoleWhat they receive
Coronary Artery Bypass Graft (CABG) groupThe study include a cohort of patients, between the ages of 65 and 80, who undergo coronary artery bypass graft surgery to treat coronary artery disease, receiving 2 or more coronary artery bypass grafts with the use of extracorporeal circulation.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Perioperative changes in microRNA 151-5p expression.

    MicroRNA-151-5p expression levels will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU. Levels of microRNA expression will be calculated relative to reference microRNA-16-5p using 2-∆∆cT method.

    Measured: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

  2. Perioperative changes in cognitive function measured by Montreal Cognitive Assessment (MoCA Test).

    Cognitive function will be assessed in all patients at enrollment one day before surgery, and daily for the following six postoperative days using the Montreal Cognitive Assessment (MoCA test).

    Montreal Cognitive Assessment scale: minimum score is 0 and maximum score is 30 points, a score of 26 or above is considered normal, while scores below this may indicate cognitive impairment. A score of 18-25 suggests mild cognitive impairment, 10-17 suggests moderate impairment, and a score 0-9 suggests severe impairment.

    Measured: 1 day before surgery and once daily postoperatively, up to the 6th postoperative day.

Secondary outcomes (7)
  1. Perioperative changes in levels of white blood cells.

    Levels of white blood cells will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.

    Measured: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission.

  2. Perioperative changes in levels of C-reactive protein.

    Levels of C-reactive protein will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.

    Measured: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

  3. Perioperative changes in levels of procalcitonin.

    Levels of procalcitonin will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.

    Measured: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

  4. Perioperative changes in levels of interleukin-6.

    Levels of interleukin-6 will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.

    Measured: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

  5. Perioperative changes in levels of cholinesterase.

    Levels of cholinesterase will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.

    Measured: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

  6. Perioperative changes in levels of protein S-100B.

    Levels of protein S-100B will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU.

    Measured: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission

  7. Patient demographic data.

    Patient demographic data: age, gender, education, and previous medical history will be recorded and correlated with microRNA expression levels, inflammatory biomarkers and the Montreal Cognitive Assessment (MoCA test) scores.

    Montreal Cognitive Assessment scale: minimum score is 0 and maximum score is 30 points, a score of 26 or above is considered normal, while scores below this may indicate cognitive impairment. A score of 18-25 suggests mild cognitive impairment, 10-17 suggests moderate impairment, and a score 0-9 suggests severe impairment.

    Measured: From enrollment to the end of cognitive testing at 6th postoperative day.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2025
  2. Study start31 May 2022
  3. Primary completion23 Jun 2023
  4. Study completion26 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
48 participants (actual)
Target duration
7 Days
IDs, dates and publications
ClinicalTrials.gov ID
NCT07231731
Sponsor's protocol ID
microRNA-POCD
Status last verified
Nov 2025
First submitted
13 Nov 2025
Last updated
19 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: After study completion, upon reasonable request, data may be shared with other researchers.

Publications

  • van Harten AE, Scheeren TW, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia. 2012 Mar;67(3):280-93. doi: 10.1111/j.1365-2044.2011.07008.x.

    PubMed 22321085
  • Kok WF, Koerts J, Tucha O, Scheeren TW, Absalom AR. Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery. Anaesthesia. 2017 Mar;72(3):359-369. doi: 10.1111/anae.13712. Epub 2016 Dec 17.

    PubMed 27987229
  • Berger M, Terrando N, Smith SK, Browndyke JN, Newman MF, Mathew JP. Neurocognitive Function after Cardiac Surgery: From Phenotypes to Mechanisms. Anesthesiology. 2018 Oct;129(4):829-851. doi: 10.1097/ALN.0000000000002194.

    PubMed 29621031
  • Greaves D, Psaltis PJ, Ross TJ, Davis D, Smith AE, Boord MS, Keage HAD. Cognitive outcomes following coronary artery bypass grafting: A systematic review and meta-analysis of 91,829 patients. Int J Cardiol. 2019 Aug 15;289:43-49. doi: 10.1016/j.ijcard.2019.04.065. Epub 2019 Apr 24.

    PubMed 31078353
  • Kapoor MC. Neurological dysfunction after cardiac surgery and cardiac intensive care admission: A narrative review part 1: The problem; nomenclature; delirium and postoperative neurocognitive disorder; and the role of cardiac surgery and anesthesia. Ann Card Anaesth. 2020 Oct-Dec;23(4):383-390. doi: 10.4103/aca.ACA_138_19.

    PubMed 33109792
  • Polito F, Fama F, Oteri R, Raffa G, Vita G, Conti A, Daniele S, Macaione V, Passalacqua M, Cardali S, Di Giorgio RM, Gioffre M, Angileri FF, Germano A, Aguennouz M. Circulating miRNAs expression as potential biomarkers of mild traumatic brain injury. Mol Biol Rep. 2020 Apr;47(4):2941-2949. doi: 10.1007/s11033-020-05386-7. Epub 2020 Mar 26.

    PubMed 32219772
  • Pozniak T, Shcharbin D, Bryszewska M. Circulating microRNAs in Medicine. Int J Mol Sci. 2022 Apr 3;23(7):3996. doi: 10.3390/ijms23073996.

    PubMed 35409354

Questions about this trial

What is this clinical trial studying?

An observational study of Biomarkers and Coronary Artery Bypass Surgery, run by Osijek University Hospital at 1 site in Croatia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Perioperative changes in microRNA 151-5p expression. (time frame: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07231731, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2025.

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