A Lithium-Based Medication to Improve Neurological Outcomes After Surgical Carotid Reconstruction

Carotid Artery Diseases Clinical Trial

Official title:

A Lithium-Based Medication to Improve Neurological Outcomes After Surgical Carotid Reconstruction: A Double-Blind, Placebo Control Randomized Trial (BINOS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05126238
• Other study ID #: BINOS
• Status: Recruiting
• Phase: Phase 3
• Start date: November 20, 2021
• Est. completion date: November 20, 2026

Study information

• Verified date: January 2024
• Source: Negovsky Reanimatology Research Institute
• Contact: Valery Likhvantsev, PhD
• Phone: +79036235982
• Email: lik0704[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There are 10.3 million cases of stroke registered in the world every year; 63% of them lead to death. According to World Health Organization, stroke is one of the most important risk factors of death and early disability.

Carotid artery surgery is a gold standard of hemodynamically significant carotid artery disease treatment. According to some trials, carotid artery surgery decreases the 2-years mortality.

The most important part of carotid artery surgery is a temporary absence of blood flow in the carotid artery. The duration of this period is a crucial characteristic of this type of surgery. The absence of blood flow leads to brain ischemia which is the risk factor of postoperative neurocognitive disorders such as emergence delirium, postoperative delirium and postoperative cognitive dysfunction.

Some surgical and non-surgical methods for brain protection were evaluated. According to recent data, there is no evidence of effective pharmacological protective methods that can decrease brain damage during carotid artery surgery.

Nevertheless, some trials demonstrated that using lithium-based medications for patients with a stroke can reduce the volume of the stroke. Therefore, the investigators want to check the hypothesis that using lithium-based medication in the preoperative period can reduce brain damage during carotid artery surgery.

The objectives of this trial:

1. To determine if Lithium carbonate is superior to placebo for the occurrence of emergence delirium, agitation, postoperative delirium and postoperative cognitive dysfunction.

2. To determine if Lithium carbonate is non-inferior to placebo for the occurrence of a new arrhythmia, leukocytosis, acute kidney injury, seizure disorders, diarrhea, nausea, and vomit.

Description:

There are 10.3 million cases of stroke registered in the world every year; 63% of them lead to death. According to World Health Organization, stroke is one of the most important risk factors of death and early disability.

Carotid artery surgery is a gold standard of hemodynamically significant carotid artery disease treatment. According to some trials, carotid artery surgery decreases the 2-years mortality.

The most important part of carotid artery surgery is a temporary absence of blood flow in the carotid artery. The duration of this period is a crucial characteristic of this type of surgery. The absence of blood flow leads to brain ischemia which is the risk factor of postoperative neurocognitive disorders such as emergence delirium, postoperative delirium and postoperative cognitive dysfunction.

Some surgical and non-surgical methods for brain protection were evaluated. According to recent data, there is no evidence of effective pharmacological protective methods that can decrease brain damage during carotid artery surgery.

Nevertheless, some trials demonstrated that using lithium-based medications for patients with a stroke can reduce the volume of the stroke. Therefore, the investigators want to check the hypothesis that using lithium-based medication in the preoperative period can reduce brain damage during carotid artery surgery.

The objectives of this trial:

To determine if Lithium carbonate is superior to placebo for the occurrence of emergence delirium, agitation, postoperative delirium and postoperative cognitive dysfunction.

To determine if Lithium carbonate is non-inferior to placebo for the occurrence of a new arrhythmia, leukocytosis, acute kidney injury, seizure disorders, diarrhea, nausea, and vomit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: November 20, 2026
• Est. primary completion date: December 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• age > 18 years

• elective carotid artery surgery

• general anesthesia

• written informed consent

Exclusion Criteria:

• urgent surgery

• recent ( < 1 month) overt stroke

• Mini-mental State Examination < 20 points

• The presence of any mental disorder according to the International Classification of Diseases 11th Revision which is confirmed by a psychiatrist.

• The presence of any neuromuscular disease according to the International Classification of Diseases 11th Revision

• Hypersensitivity or known allergy to lithium carbonate

• History of seizure disorder

• History of leukemia

• Estimated glomerular filtration rate < 30 ml/min/1.73 m2

• Left ventricular ejection fraction < 30%

• Heart failure equal 3 or 4 class according to the New York Heart Association Functional Classification

• Pregnant or breast-feeding women

• Inability to undergo a preoperative assessment for any reason

• Previously enrolled in this trial

Related Conditions & MeSH terms

• Carotid Artery Diseases
• Carotid Artery Stenosis
• Carotid Stenosis

Intervention

Drug:
• Lithium Carbonate
In preoperative period patients will take 300 mg of lithium carbonate on 1-1-1 regimen during 2 days prior to surgery. On the day of surgery they will take 300mg of lithium carbonate 2 hours before surgery.
• Placebo
In preoperative period patients will take placebo on 1-1-1 regimen during 2 days prior to surgery. On the day of surgery they will placebo 2 hours before surgery.

Locations

Country	Name	City	State
Russian Federation	Demikhov Municipal Clinical Hospital 68	Moscow
Russian Federation	Vishnevsky Center of Surgery	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
Negovsky Reanimatology Research Institute	Demikhov Municipal Clinical Hospital 68

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of emergence delirium	Number of patients with positive the confusion assessment method for the intensive care unit as soon as they reach Aldrete score of 9 points	30 days
Secondary	Frequency of agitation	Richmond agitation-sedation scale more or equal +2 evaluated from the end of volatile anesthetic supply to the moment when a patient reaches Aldrete score of 9 points; Richmond agitation-sedation scale: minimum value = -5 (Unarousable - no response to voice or physical stimulation) maximum value = +4 (Combative - overtly combative or violent; immediate danger to staff) Adequate patients have the results of Richmond agitation-sedation score equal 0 (Alert and calm; Spontaneously pays attention to caregiver)	30 days
Secondary	Frequency of postoperative delirium	Number of patients with even one positive confusion assessment method for the intensive care unit or 3-minute confusion assessment method	30 days
Secondary	Length of postoperative delirium	30 days - number of days in which patient had positive confusion assessment method for the intensive care unit or 3-minute confusion assessment method	until 1 month after surgery
Secondary	Frequency of overt strokes	Number of overt strokes	1 year
Secondary	Frequency of covert strokes	Number of covert strokes	1 year
Secondary	Length of stay in intensive care unit	Number of days in intensive care unit	1 month
Secondary	Length of hospitalization	Number of days in hospital	1 month
Secondary	Frequency of cardiac death	Number of of cardiac deaths	1 year
Secondary	Frequency of non-fatal cardiac arrest	Number of non-fatal cardiac arrests	1 year
Secondary	Frequency of major adverse cardiac event	Number of major adverse cardiac events	1 year
Secondary	Frequency of major adverse cardiac and cognitive event	Number of major adverse cardiac and cognitive events	1 year
Secondary	30-days mortality	Number of deaths in period of 30 days after surgery	30 days
Secondary	1-year mortality	Number of deaths in period of 1 year after surgery	1 year
Secondary	Frequency of new postoperative arrhythmia	Number of new postoperative arrhythmias	1 month
Secondary	Frequency of leukocytosis	Number of patients with leukocytosis	From 2 days before surgery to the day of surgery
Secondary	Frequency of acute diarrhea	Number of patients with acute diarrhea	From 2 days before surgery to the day of surgery
Secondary	Frequency of postoperative nausea and vomit	Number of patients with postoperative nausea and vomit	1 month
Secondary	Frequency of preoperative nausea and vomit	Number of patients with preoperative nausea and vomit	From 2 days before surgery to the day of surgery
Secondary	Frequency of acute kidney injury	Number of patients with acute kidney injury	1 month
Secondary	Frequency of myasthenia	Number of patients with myasthenia	From 2 days before surgery to the day of surgery
Secondary	Frequency of preoperative seizure	Number of patients with seizure	From 2 days before surgery to the day of surgery
Secondary	Frequency of postoperative seizure	Number of patients with seizure	1 month
Secondary	Serum level of S100 beta protein	Serum level of S100 beta protein	2 days after surgery
Secondary	Serum level of neuron-specific enolase	Serum level of neuron-specific enolase	2 days after surgery
Secondary	Serum level of Tau-protein	Serum level of Tau-protein	2 days after surgery
Secondary	Serum level of Neurofilament light polypeptide	Serum level of Neurofilament light polypeptide	2 days after surgery
Secondary	Serum level of Glial fibrillary acidic protein	Serum level of Glial fibrillary acidic protein	2 days after surgery