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

NCT05126238 | Terminated Phase 3 DMC

• 1 other identifier: BINOS
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

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. 1.To determine if Lithium carbonate is superior to placebo for the occurrence of emergence delirium, agitation, postoperative delirium and postoperative cognitive dysfunction.
2. 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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (27)

• Frequency of agitation

  30 days

• Frequency of postoperative delirium

  30 days

• Length of postoperative delirium

  until 1 month after surgery

• Frequency of overt strokes

  1 year

• Frequency of covert strokes

  1 year

Study Arms (2)

Lithium

EXPERIMENTAL

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.

Drug: Lithium Carbonate

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Lithium Carbonate DRUG

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.

Lithium

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age \> 18 years
• elective carotid artery surgery
• general anesthesia
• written informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Negovsky Reanimatology Research Institute: lead
• Demikhov Municipal Clinical Hospital 68: collaborator

Study Sites (1)

Demikhov Municipal Clinical Hospital 68

Moscow, Russia

Location

MeSH Terms

Conditions

Carotid Artery Diseases; Carotid Stenosis; Neurocognitive Disorders; Postoperative Cognitive Complications; Emergence Delirium; Psychomotor Agitation; Stroke; Neuroinflammatory Diseases

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arterial Occlusive Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Cognition Disorders; Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Dyskinesias; Psychomotor Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Inflammation

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Valery Likhvantsev, PhD

  Negovsky Reanimatology Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Research V. Negovsky Reanimatology Research Institute

Study Record Dates

• First Submitted: October 1, 2021
• First Posted: November 18, 2021
• Study Start: November 20, 2021
• Primary Completion: May 19, 2025
• Study Completion: May 19, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-09

Locations

RU (1)