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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Delirium; Postoperative Cognitive Dysfunction
• Intervention / Treatment: Drug: Tropisetron; Drug: Placebos

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100020
    • Recruiting
    • Beijing Chaoyang Hospital, Capital Medical University
    • Contact: Anshi Wu; Phone Number: +8685231330; Email: wuanshi1965@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written consent given
2. Scheduled to undergo elective coronary artery bypass graft surgery under general anesthesia
3. ASA Physical Score I-IV

Exclusion Criteria:

1. Inability to give informed consent.
2. Contraindications to tropisetron.
3. 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.
4. History of neuropsychiatric diseases (such as dementia, epilepsy, Parkinson's disease, or schizophrenia).
5. History of antipsychotic drug use.
6. Pre-existing severe cognitive impairment at baseline, defined as a Montreal Cognitive Assessment (MoCA) score below 10

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tropisetron; Patients allocated to this arm will receive intravenous Tropisetron (5mg) before anesthesia induction and once daily for 7 days after surgery.	Drug: Tropisetron; Investigators administrated intravenously Tropisetron 5mg before anesthesia and once daily for 7 days after surgery.
Placebo Comparator: Placebo; 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; Investigators administrated intravenously saline solution as a placebo

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of major adverse cardiac and cerebral events	Other adverse events within 30 days after surgery were noted	Within 30 days after surgery

Collaborators and Investigators

• Sponsor: Beijing Chao Yang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: November 27, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): January 5, 2022
• Last Update Submitted That Met QC Criteria: January 4, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Postoperative Complications; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Postoperative Cognitive Complications; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Tropisetron
• Other Study ID Numbers: 29847819

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No