Clinical trial NCT05126238: A Lithium-Based Medication to Improve Neurological Outcomes After Surgical Carotid Reconstruction
Official title: A Lithium-Based Medication to Improve Neurological Outcomes After Surgical Carotid Reconstruction: A Double-Blind, Placebo Control Randomized Trial (BINOS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Carotid Artery Diseases
Carotid Artery Stenosis
Keywords: Carotid artery diseases
Carotid artery stenosis
Carotid artery surgery
Lithium
Neurocognitive disorders
Postoperative cognitive disorders
Postoperative delirium
Emergence delirium
Agitation
Stroke
Neuroinflammation
Lead sponsor: Negovsky Reanimatology Research Institute
Sponsor class: OTHER_GOV
Collaborators: name: Demikhov Municipal Clinical Hospital 68
First posted: 2021-11-18
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of emergence delirium
timeFrame: 30 days
Secondary outcomes:
measure: Frequency of agitation
timeFrame: 30 days
measure: Frequency of postoperative delirium
timeFrame: 30 days
measure: Length of postoperative delirium
timeFrame: until 1 month after surgery
measure: Frequency of overt strokes
timeFrame: 1 year
measure: Frequency of covert strokes
timeFrame: 1 year
measure: Length of stay in intensive care unit
timeFrame: 1 month
measure: Length of hospitalization
timeFrame: 1 month
measure: Frequency of cardiac death
timeFrame: 1 year
measure: Frequency of non-fatal cardiac arrest
timeFrame: 1 year
measure: Frequency of major adverse cardiac event
timeFrame: 1 year
measure: Frequency of major adverse cardiac and cognitive event
timeFrame: 1 year
measure: 30-days mortality
timeFrame: 30 days
measure: 1-year mortality
timeFrame: 1 year
measure: Frequency of new postoperative arrhythmia
timeFrame: 1 month
measure: Frequency of leukocytosis
timeFrame: From 2 days before surgery to the day of surgery
measure: Frequency of acute diarrhea
timeFrame: From 2 days before surgery to the day of surgery
measure: Frequency of postoperative nausea and vomit
timeFrame: 1 month
measure: Frequency of preoperative nausea and vomit
timeFrame: From 2 days before surgery to the day of surgery
measure: Frequency of acute kidney injury
timeFrame: 1 month
measure: Frequency of myasthenia
timeFrame: From 2 days before surgery to the day of surgery
measure: Frequency of preoperative seizure
timeFrame: From 2 days before surgery to the day of surgery
measure: Frequency of postoperative seizure
timeFrame: 1 month
measure: Serum level of S100 beta protein
timeFrame: 2 days after surgery
measure: Serum level of neuron-specific enolase
timeFrame: 2 days after surgery
measure: Serum level of Tau-protein
timeFrame: 2 days after surgery
measure: Serum level of Neurofilament light polypeptide
timeFrame: 2 days after surgery
measure: Serum level of Glial fibrillary acidic protein
timeFrame: 2 days after surgery
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Vishnevsky Center of Surgery
city: Moscow
country: Russian Federation
facility: Demikhov Municipal Clinical Hospital 68
Study officials:
affiliation: Negovsky Reanimatology Research Institute
name: Valery Likhvantsev, PhD
role: PRINCIPAL_INVESTIGATOR
References: