Clinical trial NCT02979782: Neurological Outcome After Minimal Invasive Coronary Artery Bypass Graft
Official title: Neurological Outcome After Minimal Invasive Coronary Artery Bypass Graft: a Single-centre Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Postoperative Cognitive Dysfunction
Cerebrovascular Accident
Delirium
Keywords: cardiac surgery
neurological outcome
minimal invasive coronary artery bypass graft (Endo-CABG)
Lead sponsor: Jessa Hospital
Sponsor class: OTHER
Collaborators: name: Hasselt University
First posted: 2016-12-02
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The population will be divided into three groups. The first group will be the Endo-CABG group which consist of the patients who undergo minimal invasive coronary artery bypass grafting.

The second group consists of patients who will get an elective PCI intervention. this is a comparative group which is included to check whether the assessed prevalences in the Endo-CABG group are not related to underlying cardiac anomalies or to other cardiac intervention procedures.

The third group consists of healthy volunteers. This control group will be included to eliminate natural variation in neurophysiological testing and to exclude the learning effect which can occur when repeated neurophysiological testing is performed.

Brief summary: Primary objectives:

Assessment of the incidence of postoperative cognitive dysfunction (POCD), cerebrovascular accident (CVA), and delirium after minimal invasive coronary artery bypass grafting (Endo-CABG).

Secondary objectives:

* Quality of life, three months after endo-CABG
* Patient satisfaction with endo-CABG and the tests performed
* The influence of various demographic and peri-operative variables on neurological outcome after endo-CABG
* Incidence of fear and depression, 3 months after endo-CABG

Detailed description: Introduction:

Major improvements in surgical techniques, perfusion systems, and perioperative policies have led to improved quality of life of the patient, lower hospitalisation costs, and lower mortality rates in the field of cardiac surgery. However, despite these improvements and improved postoperative care, the neurological outcome after cardiac surgery remains a recurrent issue of interest. The most common neurological disorders after cardiac surgery are postoperative cognitive dysfunction (POCD), cerebrovascular accident (CVA), and delirium. After conventional cardiac surgery (invasive sternotomy procedure) the incidence of these neurological disorders is well studied. POCD has an incidence of 25-50%, CVA has an incidence of 1-5% and delirium has an incidence of 5-15%. These numbers prove that neurological outcome still is a major problem after cardiac surgery.

Postoperative cognitive dysfunction (POCD) is the most common neurological disorder after cardiac surgery. POCD is defined as a disturbance of the brain function, which is causally related to surgery. Due to the multifactorial nature of POCD it is difficult to pinpoint one major cause. testing of POCD is not standardised and is based on the '1995 statement of concensus on assessment of neurobehavioural outcomes after cardiac surgery'. This consensus statement describes the most reliable tests and study design to study POCD in clinical studies.

A battery of tests is described in the consensus statement:

* Rey auditory verbal learning test for verbal memory
* Trailmaking A and B for attention
* Grooved pegboard test for fine motor function

In this study, two additional tests will be performed to assess POCD:

the digit span test to test the short term verbal memory. the digit symbol-coding test to test the processing speed and memory of the patient.

Additional recommendations of the consensus statement to conduct reliable POCD testing are:

* Baseline testing
* At least on assessment of POCD three months postoperatively
* A control group and a comparative group
* The same person tests both pre- and postoperatively
* a clinical neurological investigation is necessary

Cerebrovascular accident (CVA or stroke) is caused by disturbances of the brain blood supply. The main causes of these disturbances are clotted vessels, hypoperfusion, or ruptured vessels in the brain. The risk of CVA is high in the first few days after cardiac surgery. CVA is diagnosed based on neurological evaluation and signs on CT or MRI scan.

Delirium is characterised by attention disorders and fluctuating changes in the mental state of the patient. Delirium is mainly related to surgery and can be diagnosed with the CAM-ICU (confusion assessment method for the intensive care unit).

These neurological complications have a negative effect on the quality of life, healthcare costs and mortality rate after cardiac surgery.

Recently, new developments in cardiac surgery hav led to the introduction of minimal invasive cardiac procedures into practice. These minimal invasive cardiac procedures are proven to be beneficial for the patient. Neurological outcome after minimal invasive cardiac surgery however, is not well studied.

Therefore, the main goal of this study is to examine the neurological outcome after endoscopic coronary artery bypass grafting (Endo-CABG). Endo-CABG is a minimal invasive cardiac procedure based on the conventional coronary artery bypass grafting (CABG) procedure.

Study design and study tests:

This study will be a single-centre prospective cohort study. The goal of the study is to assess the neurological outcome after endoscopic coronary artery bypass grafting (Endo-CABG). Three study groups will be included (described in section study groups), which will be tested for POCD, CVA and delirium.

Secondary outcomes in this research are quality of life of the patient (EQ-5D-5L), Fear and depression outcomes (VVO; CES-D), and assessment of demographic and peri-operative predictors of poor neurological outcome after endo-CABG.

Study tests:

Baseline tests will be performed in both intervention groups (Endo-CABG and PCI) and the healthy control group.

In the intervention groups the baseline preoperative tests will include:

* Baseline neurocognitive status: mini mental test
* Baseline EQ-5D: Quality of life
* Baseline fear and depression state (VVO; CES-D)
* Preoperative clinical neurological investigation
* Baseline POCD status (Rey auditory verbal learning test,Trailmaking A \& B, Grooved pegboard test, Digit span test, Digit symbol-coding test)

For the healthy volunteers the same baseline tests will be performed, with exception of the neurological clinical evaluation.

Postoperative tests in the intervention groups will include:

* Postoperative neurologic clinical evaluation (CT scan if CVA suspected), CAM-ICU): these tests will be performed at the ICU or ward
* 3 months after surgery: EQ-5d (quality of life), Fear and depression, POCD follow-up (Rey auditory verbal learning test, Trailmaking A \& B, Grooved pegboard test, Digit span test, Digit symbol-coding test)

For the healthy volunteers, the following tests will be performed 3 months after baseline testing:

* EQ-5d: quality of life
* Stroke follow-up
* Fear and depression
* POCD status (Rey auditory verbal learning test,Trailmaking A \& B, Grooved pegboard test, Digit span test, Digit symbol-coding test)

Statistical analysis:

In this study POCD is defined as a decline in score between baseline and follow-up neurophysiological test, which should be higher than the natural variation. In this setting the natural learning effect will also be taken into account. To perform statistical analysis for POCD testing, Z-scores (or reliable change index (RCI)) will be used. The Z-score is a unit which indicates how the difference between the baseline score and the follow-up test behaves compared to the mean scores of the control group.

Thus, the individual RCI scores will be calculated as follows:

* For each patient, the baseline score from each test will be subtracted from the follow-up score, giving Δx. The same will be done in the control group, giving Δxc. The mean change on that test in the control group will then be subtracted from Δx to eliminate practice effects.
* This result will then be divided by the standard deviation of Δxc to eliminate the effect of natural variation in test performance. This is called a Z-score.

The RCI is the sum of the Z-scores of all tests.

We defined POCD in an individual patient as an RCI equal to or less than -1.645 (significance level 5%), or Z-score equal to or less than -1.645 in at least two different tests.

The group RCI scores will be compared using ANOVA or Kruskall-Wallis.

The quality of life will be tested using a mann-whitney U test at significance level 5%.

Eligibility criteria: Inclusion Criteria:

* Minimum age of 18
* Elective Endo-CABG procedure (group 1)
* Elective PCI procedure (group 2)
* Elective healthy volunteer

Exclusion Criteria:

* Medical history of:
* Postoperative cognitive dysfunction, delirium or cerebrovascular accident
* symptomatic carotid artery disease
* Dementia
* Renal dysfunction: glomular filtration rate (GFR) \< 30 ml/min
* Hepatic dysfunction: serum glutamic-oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST), or serum glutamic-pyruvic transaminase (SGPT)/ alanine aminotransferase (ALT), more than three timer higher than normal limits
* History of medication and alcohol abuse
* Language barrier or incapability to communicate
* Physical condition making participation impossible
* Participation in other clinical trials of a drug or medical instrument
* Surgical revision or intra-operative major cardial event (Endo-CABG group)
* Conversion to cardiac surgery or intra-operative major event (PCI group)

Primary outcomes:
measure: Prevalence of postoperative cognitive dysfunction
timeFrame: 3 months after intervention
measure: Prevalence of delirium
timeFrame: 3 months after intervention
measure: Prevalence of cerebrovascular accident
timeFrame: 3 months after intervention
Secondary outcomes:
measure: Quality of life of the patient
timeFrame: 3 months after intervention
measure: assessment of predictors of poor neurological outcome after minimal invasive coronary artery bypass grafting
timeFrame: 3 months after intervention
measure: Incidence of depression after minimal invasive coronary artery bypass grafting
timeFrame: 3 months after intervention
measure: Incidence of fear after minimal invasive coronary artery bypass grafting
timeFrame: 3 months after intervention
Other outcomes:
Locations:
city: Hasselt
country: Belgium
facility: Jessa Hospital
state: Limburg
city: Hasselt
country: Belgium
facility: Jessaziekenhuis Hasselt
state: Limburg
Study officials:
affiliation: bjornstessel@hotmail.com
name: Björn Stessel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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