The Role of Neuroinflammation on Neurocognitive Outcome in Cardiac Surgery

NCT07200726 | Recruiting

• 1 other identifier: Z-2025013
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Postoperative cognitive changes are common after cardiac surgery and can be categorised into three main types: postoperative delirium (POD), delayed neurocognitive recovery (DNCR) and postoperative neurocognitive disorder (PNCD). DNCR is diagnosed until postoperative day 30 and PNCD is diagnosed at least 30 days after the operation. Both conditions can be mild or major, and can affect the quality of life of these patients. The incidence of PNCD in cardiac surgery is around 40%. Despite this high incidence, screening for PNCD is absent in current postoperative care since the diagnosis of PNCD is difficult and very time intensive. Furthermore, the underlying pathogenesis is incompletely understood. The identification of a biomarker and/or validated short diagnostic instrument would be of paramount importance to easily identify patients at risk, or to diagnose patients with PNCD in order to identify therapeutical pathways for this disease. OBJECTIVES: The main objective of this prospective clinical trial is to evaluate the performance of the short NPA and/or biochemical markers for the diagnosis of DNCR and PNCD in cardiac surgery patients aged 60 years or older. STUDY DESIGN: Single-centre interventional observational study STUDY INTERVENTIONS: Patients will undergo a neurophysiological assessment (NPA) pre-operatively and at two timepoints post-operatively, namely 6 (+/-1) days and 40 (+/- 10) days after surgery. During the stay at the intensive care unit, they will be screened daily for delirium, using the CAM-ICU and 3D-CAM. To evaluate whether the development of DNCR or POD has an important effect on quality of recovery , the quality of recovery scale 15 (QOR-15), muscle strength (handgrip strength) and the Chalder fatigue score will be scored post-operative (postop day 1, 3 and 5). To evaluate whether PNCD has an effect on quality of live the EQ5D5L score will be measured at 40 (+/- 10) days after surgery, compared to preoperative values. On several time points, blood samples will be drawn to measure markers of neuroinflammation. The time points will be preoperatively, at the moment of arrival on ICU, postoperative day 1, 2 and 3, if still on ICU. Two repeat blood sample will be taken at the moment of NPA performed after 6 (+/- 1) days and 40 (+/- 10) days after surgery, if the patient is willing (not obligatory). STUDY POPULATION: Patients aged 60 years or older who are scheduled for cardiac surgery. Inclusion criteria:

• aged 60 years or older;
• scheduled for cardiac surgery. Exclusion criteria:
• dementia, as diagnosed by a neurologist;
• urgent, not elective surgery. MAIN STUDY ENDPOINTS: Primary outcome PNCD defined as a decline of \> 1 SD on \> 2 tests in one or more cognitive domains or a decline of \> 1 SD on total cognitive domain score. Secondary outcomes Postoperative delirium - CAM-ICU will be evaluated twice daily (morning and evening) on every day when the patient is awake (not intubated) on the ICU. This is standard of care and is part of the routine clinical care in the hospital. Furthermore, once daily a 3D-CAM will be performed on day 1, 3 and 5. Quality of recovery
• QOR-15, a validated measurement of quality of recovery in the short term postoperative recovery, will be evaluated pre-operatively and postoperatively day 1, 3 and 5.
• EQ5D5L, a validated measurement of quality of recovery in the long term postoperative recovery, will be evaluated preoperatively and at the moment of the third NPA measurement.
• Postoperative muscle function (upper extremity, by hand grip strength) on day 1, 3 and 5 after surgery and at the moment of the second and third NPA measurement (being day 6 (+/-1) and day 40 (+/-10) postoperatively), as compared to preoperative values.
• Chalder Fatigue questionnaire on day 1, 3 and day 5 and on the second and third NPA measurement, as compared to preoperative. Biochemical analysis \- Blood samples will be drawn for analysis before induction of anaesthesia (preoperatively), at the end of the operation (immediately postoperatively on arrival in ICU), on day 1, 2 and 3 postoperatively (if still at the ICU) and at the time of the postoperative follow-up visits with the NPA testing (day 6 (+/-1) and day 40 (+/-10) days post-surgery). At each time point, markers of neuroinflammation and -degeneration will be determined. Tertiary outcomes
• Length of CPB
• Duration of mechanical ventilation
• Administered anaesthetic drugs during surgery
• Transfusion need
• Length of ICU stay (days)
• Length of in-hospital stay (days)
• Readmission to ICU or hospital within 28 days after surgery
• Cardiovascular outcome: atrial fibrillation, , thrombo-embolic events, myocardial injury, myocardial infarction, cardiac arrest, cardiac death
• Pulmonary outcome: postoperative pulmonary complications, postoperative pneumonia, postoperative respiratory failure
• Postoperative infection within 28 days after surgery

Conditions

Major Surgery Under General Anesthesia; Major Surgery in Adult Patients; Elderly Patients; Quality of Recovery; Postoperative Neurocognitive Dysfunction; Postoperative Neurocognitive Disorder; Postoperative Fatigue; Cardiac Surgery

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative neurocognitive disorder (PNCD) after cardiac surgery using the NPA.

  The neuropsychological assessment (NPA) consists of 17 subsets which can be divided into five cognitive domains: speed and attention, memory, language, executive and visuospatial functioning. The outcomes are 21 scores, namely the scores of the 17 subsets and 4 combined scores. These are reported in T-scores after correction for age and educational level by comparison with a norm group. PNCD is defined as a decline of \> 1 SD on \> 2 tests in one or more cognitive domains or a decline of \> 1 SD on total cognitive domain score.

  The NPA will be taken preoperatively and postoperatively on day 40 (+/- 10).

Secondary Outcomes (10)

• Delayed neurocognitive recovery (DNCR)

  Day 6 (+/- 1) following surgery.

• Postoperative delirium (CAM-ICU)

  Twice daily (morning and evening) day 1 - day 5 following surgery if the patient is still in the ICU.

• Postoperative delirium (3D-CAM)

  Postoperative day 1, day 3 and day 5.

• Quality of recovery (QoR-15)

  Preoperative, postoperative day 1, day 3 and day 5.

• Postoperative muscle strength (HGS)

  Preoperative, postoperative day 1, day 3, day 5, day 6 (+/- 1), and day 40 (+/- 10).

Interventions

Observational study design - no intervention OTHER

Observational study design - no intervention

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Since, compared to younger patients undergoing major surgery, elderly patients are more prone to develop PNCD and are at greater risk of morbidity, we will therefore include patients aged 60 years or older scheduled for cardiac surgery.

You may qualify if:

• aged 60 years or older;
• scheduled for cardiac surgery.

You may not qualify if:

• dementia, as diagnosed by a specialist, since this would make detection of PNCD impossible;
• urgent, not elective surgery.

Sponsors & Collaborators

• Ziekenhuis Oost-Limburg: lead

Study Sites (1)

Ziekenhuis Oost-Limburg

Genk, Limburg, 3600, Belgium

RECRUITING

Central Study Contacts

Steven Thiessen, MD, PhD

CONTACT

3289804646; steven.thiessen@zol.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2025
• First Posted: October 1, 2025
• Study Start: October 21, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 8, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)