A Pilot Trial Evaluating the Effect of Tropisetron on Postoperative Cognitive Dysfunction After Cardiac Surgery

Study Overview
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Brief Summary
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The purpose of this study is to assess the feasibility of a randomized, double-blind, placebo-controlled pilot trial evaluating the effect of tropisetron on prevention of postoperative cognitive dysfunction in patients after cardiac surgery.

Detailed Description
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Postoperative cognitive dysfunction is a common complication during postoperative period，especially in elderly patients. It is characterized by cognitive decline, inattention and abnormal mental status following surgery. The presence of postoperative cognitive dysfunction is independently associated with poor recovery, increased hospital length of stay and increased mortality. Tropisetron is a 5-HT3A receptor antagonist and is widely used to treat postoperative nausea and vomiting. Previous studies found that tropisetron has positive effect on cognitive function. We have designed a randomized, double-blind, placebo-controlled trial to determine if tropisetron has a positive effect on postoperative coginitive function in patients after cardiac surgery. Several assessements which are related to delirium, cognitive function, sleep and functional status, blood sample collection and EEG recordings will be involved in the trial. Moreover, we have assumed a few long-term follow-ups. Given the complexity of the trial, we have decided to implement a pilot trial to assess the feasibility and provide vital data for future formal trial.

Official Title
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A Randomized, Double-blind, Placebo-controlled Pilot Trial Evaluating the Effect of Tropisetron on Prevention of Postoperative Cognitive Dysfunction in Patients After Cardiac Surgery

Conditions
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Postoperative Cognitive Dysfunction, Postoperative Delirium

Intervention / Treatment
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* Drug: Tropisetron
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written consent given Scheduled to undergo elective coronary artery bypass graft surgery under general anesthesia ASA Physical Score I-IV Exclusion Criteria: Inability to give informed consent. Contraindications to tropisetron. Critical preoperative state, including preoperative left ventricular ejection fraction less than 30%, ventricular tachycardia or ventricular fibrillation, preoperative cardiopulmonary resuscitation, preoperative intra-aortic balloon pump (IABP) or mechanical circulatory requirement. History of neuropsychiatric diseases (such as dementia, epilepsy, Parkinson's disease, or schizophrenia). History of antipsychotic drug use. Pre-existing severe cognitive impairment at baseline, defined as a Montreal Cognitive Assessment (MoCA) score below 10

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tropisetron<br>Patients allocated to this arm will receive intravenous Tropisetron (5mg) before anesthesia induction and once daily for 7 days after surgery. | Drug: Tropisetron<br>* Investigators administrated intravenously Tropisetron 5mg before anesthesia and once daily for 7 days after surgery.<br>|
| Placebo Comparator: Placebo<br>Patients allocated to this arm will receive an identical volume of normal saline before anesthesia and once daily for 7 days after surgery. | Drug: Placebos<br>* Investigators administrated intravenously saline solution as a placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The feasibility of tropisetron intervention on POCD in patients after cardiac surgery | The feasibility will mainly be determined by the percentage of participants who completed the whole study procedure from recruitment to the 1-month follow-up. | Within 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative cognitive dysfunction | Screening of the patients regarding a POCD by Repeatable Battery Neuropsychological Status (RBANS). Besides, the changes in SCWT and IRI scores will be an additional indication of POCD. | One day before surgery, discharge from hospital and 1 month after surgery | 
| Incidence of postoperative delirium | Screening of the patients regarding a postoperative delirium by The Confusion Assessment Method for The Intensive Care Unit (CAM-ICU) | Within 7 days after surgery | 
| Functional status measurement | Screening of the patients by Barthel Index scale ranging from 0 to 100, where less than 20 indicates total dependence, 20-35 scores indicate severe dependence, 40-55 scores indicate moderate dependence, equal or over 60 indicates mild dependency and 100 indicates independence. | One day before surgery and 1 month after surgery | 
| EEG frequency spectrum | Electroencephalography will be recorded at different points of time as follows and EEG characteristics including power in alpha, beta, theta, delta, gamma, spectrum will be extracted using MATLAB: before anesthesia introduction during anesthesia 1 day after surgery 2 days after surgery 3 days after surgery | Within 3 days after surgery | 
| Postoperative Pain | Visual Analogue Scale will be used to assess postoperative pain of patients. Numerical rating scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst pain. | Within 7 days after surgery | 
| Sleep Quality | Sleep diary and subjective sleep quality scores（Visual Analogue Scale） will be used to assess postoperative sleep quality of patients within 7 days after surgery. Chinese version of the Pittsburgh sleep quality index (PSQI) will be used to assess sleep quality and disturbances. Nineteen individual items generate seven component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. The total score is between 0 and 21. The total score ≤ 5 indicates good sleep quality，> 5 indicates poor sleep quality. PSQI will be recorded at different points of time as follows： 1 day before surgery 30 days after surgery | Within 30 days after surgery | 
| Incidence of postoperative nausea and vomiting |  | Within 7 days after surgery | 
| Length of ICU stay |  | From the date of admission until discharged from ICU, up to 30 days | 
| Length of Hospital stay |  | From the date of admission until discharged from hospital, up to 30 days | 
| Incidence of major adverse cardiac and cerebral events | MACCE comprises all-cause mortality, myocardial infarction, repeat unplanned revascularization (surgical revision or percutaneous transluminal coronary angioplasty), and stroke | Within 30 days after surgery | 
| Inflammatory biomarkers | lood samples will be collected at different points of time as follows: before anesthesia introduction 1 day after surgery 3 days after surgery 7 days after surgery Levels of serum biomarkers, including but not limited to, interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)α, Interferon (IFN)γ, Tau, vascular endothelial growth factor (VEGF)D and brain-derived neurotrophic factor (BDNF) will be examined using these specimens | Within 7 days after surgery |