A Lithium-Based Medication to Improve Neurological Outcomes After Surgical Carotid Reconstruction: A Double-Blind, Placebo Control Randomized Trial (BINOS)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 107
- 试验地点
- 1
- 主要终点
- Frequency of emergence delirium
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age > 18 years
- •elective carotid artery surgery
- •general anesthesia
- •written informed consent
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Lithium Carbonate (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 take placebo 2 hours before surgery. After the surgery, patients will take placebo in the afternoon and in the evening.
干预措施: Placebo (Drug)
结局指标
主要结局
Frequency of emergence delirium
时间窗: 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
次要结局
- Serum level of Tau-protein(2 days after surgery)
- Length of postoperative delirium(until 1 month after surgery)
- Frequency of covert strokes(1 year)
- Frequency of major adverse cardiac event(1 year)
- Serum level of neuron-specific enolase(2 days after surgery)
- Frequency of preoperative seizure(From 2 days before surgery to the day of surgery)
- Length of hospitalization(1 month)
- Frequency of leukocytosis(From 2 days before surgery to the day of surgery)
- Frequency of postoperative nausea and vomit(1 month)
- Frequency of postoperative delirium(30 days)
- Frequency of cardiac death(1 year)
- Frequency of non-fatal cardiac arrest(1 year)
- 1-year mortality(1 year)
- Frequency of acute diarrhea(From 2 days before surgery to the day of surgery)
- Frequency of agitation(30 days)
- Length of stay in intensive care unit(1 month)
- Frequency of preoperative nausea and vomit(From 2 days before surgery to the day of surgery)
- Frequency of acute kidney injury(1 month)
- Frequency of myasthenia(From 2 days before surgery to the day of surgery)
- Serum level of S100 beta protein(2 days after surgery)
- Serum level of Neurofilament light polypeptide(2 days after surgery)
- Serum level of Glial fibrillary acidic protein(2 days after surgery)
- Frequency of overt strokes(1 year)
- Frequency of major adverse cardiac and cognitive event(1 year)
- 30-days mortality(30 days)
- Frequency of new postoperative arrhythmia(1 month)
- Frequency of postoperative seizure(1 month)
研究者
Valery Likhvantsev, MD
Head of the Research V. Negovsky Reanimatology Research Institute
Negovsky Reanimatology Research Institute