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

Negovsky Reanimatology Research Institute

Status and phase: Terminated; Phase 3

Conditions: Carotid Artery Stenosis; Carotid Artery Diseases

Treatments: Drug: Lithium Carbonate; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05126238

BINOS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 107 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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107 participants in 2 patient groups, including a placebo group

Lithium

Experimental group

Description:

In preoperative period patients will take 300mg 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. After the surgery, patients will take 300mg of lithium carbonate in the afternoon and 300mg of lithium carbonate in the evening.

Treatment:

Drug: Lithium Carbonate

Placebo

Placebo Comparator group

Description:

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 take placebo 2 hours before surgery. After the surgery, patients will take placebo in the afternoon and in the evening.

Treatment:

Drug: Placebo