Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05126238
Recruitment Status : Recruiting
First Posted : November 18, 2021
Last Update Posted : March 18, 2022
Sponsor:
Collaborator:
Demikhov Municipal Clinical Hospital 68
Information provided by (Responsible Party):
Valery Likhvantsev, MD, Negovsky Reanimatology Research Institute

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.

Condition or disease Intervention/treatment Phase
Carotid Artery Diseases Carotid Artery Stenosis Drug: Lithium Carbonate Drug: Placebo Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Lithium-Based Medication to Improve Neurological Outcomes After Surgical Carotid Reconstruction: A Double-Blind, Placebo Control Randomized Trial (BINOS)
Actual Study Start Date : November 20, 2021
Estimated Primary Completion Date : December 20, 2023
Estimated Study Completion Date : November 20, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Lithium
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
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 Comparator: 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 take placebo 2 hours before surgery. After the surgery, patients will take placebo in the afternoon and in the evening.
Drug: 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.




Primary Outcome Measures :
  1. Frequency of emergence delirium [ Time Frame: 30 days ]
    Number of patients with positive the confusion assessment method for the intensive care unit as soon as they reach Aldrete score of 9 points


Secondary Outcome Measures :
  1. Frequency of agitation [ Time Frame: 30 days ]

    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)


  2. Frequency of postoperative delirium [ Time Frame: 30 days ]
    Number of patients with even one positive confusion assessment method for the intensive care unit or 3-minute confusion assessment method

  3. Length of postoperative delirium [ Time Frame: until 1 month after surgery ]
    30 days - number of days in which patient had positive confusion assessment method for the intensive care unit or 3-minute confusion assessment method

  4. Frequency of overt strokes [ Time Frame: 1 year ]
    Number of overt strokes

  5. Frequency of covert strokes [ Time Frame: 1 year ]
    Number of covert strokes

  6. Length of stay in intensive care unit [ Time Frame: 1 month ]
    Number of days in intensive care unit

  7. Length of hospitalization [ Time Frame: 1 month ]
    Number of days in hospital

  8. Frequency of cardiac death [ Time Frame: 1 year ]
    Number of of cardiac deaths

  9. Frequency of non-fatal cardiac arrest [ Time Frame: 1 year ]
    Number of non-fatal cardiac arrests

  10. Frequency of major adverse cardiac event [ Time Frame: 1 year ]
    Number of major adverse cardiac events

  11. Frequency of major adverse cardiac and cognitive event [ Time Frame: 1 year ]
    Number of major adverse cardiac and cognitive events

  12. 30-days mortality [ Time Frame: 30 days ]
    Number of deaths in period of 30 days after surgery

  13. 1-year mortality [ Time Frame: 1 year ]
    Number of deaths in period of 1 year after surgery

  14. Frequency of new postoperative arrhythmia [ Time Frame: 1 month ]
    Number of new postoperative arrhythmias

  15. Frequency of leukocytosis [ Time Frame: From 2 days before surgery to the day of surgery ]
    Number of patients with leukocytosis

  16. Frequency of acute diarrhea [ Time Frame: From 2 days before surgery to the day of surgery ]
    Number of patients with acute diarrhea

  17. Frequency of postoperative nausea and vomit [ Time Frame: 1 month ]
    Number of patients with postoperative nausea and vomit

  18. Frequency of preoperative nausea and vomit [ Time Frame: From 2 days before surgery to the day of surgery ]
    Number of patients with preoperative nausea and vomit

  19. Frequency of acute kidney injury [ Time Frame: 1 month ]
    Number of patients with acute kidney injury

  20. Frequency of myasthenia [ Time Frame: From 2 days before surgery to the day of surgery ]
    Number of patients with myasthenia

  21. Frequency of preoperative seizure [ Time Frame: From 2 days before surgery to the day of surgery ]
    Number of patients with seizure

  22. Frequency of postoperative seizure [ Time Frame: 1 month ]
    Number of patients with seizure

  23. Serum level of S100 beta protein [ Time Frame: 2 days after surgery ]
    Serum level of S100 beta protein

  24. Serum level of neuron-specific enolase [ Time Frame: 2 days after surgery ]
    Serum level of neuron-specific enolase

  25. Serum level of Tau-protein [ Time Frame: 2 days after surgery ]
    Serum level of Tau-protein

  26. Serum level of Neurofilament light polypeptide [ Time Frame: 2 days after surgery ]
    Serum level of Neurofilament light polypeptide

  27. Serum level of Glial fibrillary acidic protein [ Time Frame: 2 days after surgery ]
    Serum level of Glial fibrillary acidic protein



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05126238


Contacts
Layout table for location contacts
Contact: Valery Likhvantsev, PhD +79036235982 lik0704@gmail.com
Contact: Levan Berikashvili, MD +79263308968 levan.berikashvili@mail.ru

Locations
Layout table for location information
Russian Federation
Demikhov Municipal Clinical Hospital 68 Recruiting
Moscow, Russian Federation
Contact: Levan Berikashvili    +79263308968    levan.berikashvili@mail.ru   
Sponsors and Collaborators
Negovsky Reanimatology Research Institute
Demikhov Municipal Clinical Hospital 68
Investigators
Layout table for investigator information
Principal Investigator: Valery Likhvantsev, PhD Negovsky Reanimatology Research Institute
Layout table for additonal information
Responsible Party: Valery Likhvantsev, MD, Head of the Research V. Negovsky Reanimatology Research Institute, Negovsky Reanimatology Research Institute
ClinicalTrials.gov Identifier: NCT05126238    
Other Study ID Numbers: BINOS
First Posted: November 18, 2021    Key Record Dates
Last Update Posted: March 18, 2022
Last Verified: March 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Valery Likhvantsev, MD, Negovsky Reanimatology Research Institute:
Carotid artery diseases
Carotid artery stenosis
Carotid artery surgery
Lithium
Neurocognitive disorders
Postoperative cognitive disorders
Postoperative delirium
Emergence delirium
Agitation
Stroke
Neuroinflammation
Additional relevant MeSH terms:
Layout table for MeSH terms
Carotid Stenosis
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs