A Lithium-Based Medication to Improve Neurological Outcomes After Surgical Carotid Reconstruction
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| ClinicalTrials.gov Identifier: NCT05126238 |
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Recruitment Status :
Recruiting
First Posted : November 18, 2021
Last Update Posted : March 18, 2022
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Carotid Artery Diseases Carotid Artery Stenosis | Drug: Lithium Carbonate Drug: Placebo | Phase 3 |
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.
| 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 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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. |
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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.
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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. |
- 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
- 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)
- 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
- 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
- Frequency of overt strokes [ Time Frame: 1 year ]Number of overt strokes
- Frequency of covert strokes [ Time Frame: 1 year ]Number of covert strokes
- Length of stay in intensive care unit [ Time Frame: 1 month ]Number of days in intensive care unit
- Length of hospitalization [ Time Frame: 1 month ]Number of days in hospital
- Frequency of cardiac death [ Time Frame: 1 year ]Number of of cardiac deaths
- Frequency of non-fatal cardiac arrest [ Time Frame: 1 year ]Number of non-fatal cardiac arrests
- Frequency of major adverse cardiac event [ Time Frame: 1 year ]Number of major adverse cardiac events
- Frequency of major adverse cardiac and cognitive event [ Time Frame: 1 year ]Number of major adverse cardiac and cognitive events
- 30-days mortality [ Time Frame: 30 days ]Number of deaths in period of 30 days after surgery
- 1-year mortality [ Time Frame: 1 year ]Number of deaths in period of 1 year after surgery
- Frequency of new postoperative arrhythmia [ Time Frame: 1 month ]Number of new postoperative arrhythmias
- Frequency of leukocytosis [ Time Frame: From 2 days before surgery to the day of surgery ]Number of patients with leukocytosis
- Frequency of acute diarrhea [ Time Frame: From 2 days before surgery to the day of surgery ]Number of patients with acute diarrhea
- Frequency of postoperative nausea and vomit [ Time Frame: 1 month ]Number of patients with postoperative nausea and vomit
- 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
- Frequency of acute kidney injury [ Time Frame: 1 month ]Number of patients with acute kidney injury
- Frequency of myasthenia [ Time Frame: From 2 days before surgery to the day of surgery ]Number of patients with myasthenia
- Frequency of preoperative seizure [ Time Frame: From 2 days before surgery to the day of surgery ]Number of patients with seizure
- Frequency of postoperative seizure [ Time Frame: 1 month ]Number of patients with seizure
- Serum level of S100 beta protein [ Time Frame: 2 days after surgery ]Serum level of S100 beta protein
- Serum level of neuron-specific enolase [ Time Frame: 2 days after surgery ]Serum level of neuron-specific enolase
- Serum level of Tau-protein [ Time Frame: 2 days after surgery ]Serum level of Tau-protein
- Serum level of Neurofilament light polypeptide [ Time Frame: 2 days after surgery ]Serum level of Neurofilament light polypeptide
- Serum level of Glial fibrillary acidic protein [ Time Frame: 2 days after surgery ]Serum level of Glial fibrillary acidic protein
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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
| Contact: Valery Likhvantsev, PhD | +79036235982 | lik0704@gmail.com | |
| Contact: Levan Berikashvili, MD | +79263308968 | levan.berikashvili@mail.ru |
| Russian Federation | |
| Demikhov Municipal Clinical Hospital 68 | Recruiting |
| Moscow, Russian Federation | |
| Contact: Levan Berikashvili +79263308968 levan.berikashvili@mail.ru | |
| Principal Investigator: | Valery Likhvantsev, PhD | Negovsky Reanimatology Research Institute |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Carotid artery diseases Carotid artery stenosis Carotid artery surgery Lithium Neurocognitive disorders Postoperative cognitive disorders |
Postoperative delirium Emergence delirium Agitation Stroke Neuroinflammation |
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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 |