Safety and Efficacy of Bovis Calculus Stativus in the Treatment of Acute Cerebral Ischemic Stroke With Impaired Consciousness- A Multicenter, Prospective, Double-blind, Randomized Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 220
- 主要终点
- Proportion of patients with GCS improvement ≥2 points
研究概览
简要总结
Acute ischemic stroke (AIS) is a severe and life-threatening condition, with 35% of AIS patients experiencing impaired consciousness upon admission within 24 hours of onset. Previous studies indicated that patients with impaired consciousness at the onset of stroke have a higher incidence of stroke-related complications, particularly cerebral edema and pneumonia, as well as higher in-hospital and three-month mortality rates. The etiology of impaired consciousness in AIS is complex: ischemic damage to reticular activating system of the brainstem can directly lead to cell necrosis and result in impaired consciousness. Furthermore, secondary pathological changes following AIS, such as excitatory amino acid toxicity, oxidative stress, free radical production, and cascading inflammatory responses, can indirectly worsen impaired consciousness. Therefore, impaired consciousness at the onset of AIS is the result of cellular damage under multiple pathophysiological mechanisms. Developing neuroprotective drugs with multiple targets is key to effectively improving adverse outcomes related to impaired consciousness in AIS. However, there is currently a lack of treatment specifically aimed at improving impaired consciousness at the onset of AIS.
Cultivated Bovine Bezoar (Bovis Calculus Stativus, BCS) combines the advantages of pharmacological similarity to natural bovine by adding components such as deoxycholic acid, cholic acid, and composite calcium bilirubin to fresh bovine bile. It is rich in various trace elements and amino acids and is a compound medication that can exert neuroprotective effects through multiple pathways and targets. In traditional Chinese medicine, it has long been used to treat various consciousness disorder-related diseases, including stroke. The various components of in vitro cultivated bezoar are also widely used in clinical research for various neurological diseases.The above evidence fully demonstrates that BCS is an optimal treatment for impaired consciousness in stroke.
The goal of this clinical trial is to learn if Bovis Calculus Stativus works to treat acute cerebral ischemic stroke with impaired consciousness. It will also learn about the safety of Bovis Calculus Stativus. The main questions it aims to answer are:
- Does Bovis Calculus Stativus treat and alleviate consciousness disorders in patients with acute cerebral infarction accompanied by impaired consciousness ？
- What medical problems do participants have when taking Bovis Calculus Stativus?
Researchers will compare Bovis Calculus Stativus to a placebo (a look-alike substance that contains no drug) to see if Bovis Calculus Stativus works to treat acute cerebral ischemic stroke with impaired consciousness.
Participants will:
- receive treatment with Bovis Calculus Stativus (or placebo) for 5 days.
- Take an in-person or telephone follow-up within 90 days after the acute stroke.
详细描述
This study evaluates whether the combination of Bovis Calculus Stativus (BCS) with conventional treatment can improve impaired consciousness and functional outcomes, and whether it increases serious adverse events in patients with acute cerebral infarction accompanied by impaired consciousness within 72 hours of onset. This is a prospective multicenter randomized controlled double-blind study. In 12 centers in China,220 patients with the following situations will be enrolled: acute ischemic stroke accompanied by impaired consciousness within 72 hours and a GCS score of 3-12. Patients will be randomly assigned into 2 groups according to the ratio of 1:1:
- Experimental Group:
Patients with acute ischemic stroke accompanied by impaired consciousness within 72 hours and a Glasgow Coma Scale (GCS) score of 3-12, who are randomized to the experimental group, will be administered 0.6 g of BCS orally or via nasogastric tube immediately after recruitment. Subsequently, in accordance with guidelines, they will receive standard acute stroke treatment along with 0.6 g of BCS twice daily (bid) orally or via nasogastric tube for 5 consecutive days. 2. Placebo Control Group:
Patients with acute ischemic stroke accompanied by impaired consciousness within 72 hours and a GCS score of 3-12, who are randomized to the control group, will be administered a placebo following the same regimen immediately after recruitment. Subsequently, in accordance with guidelines, they will receive standard acute stroke treatment along with the placebo administered orally or via nasogastric tube for 5 consecutive days.
Patients will be assessed using the GCS and NIHSS scores at 24 hours and 8 days after randomization, and the mRS score at 8 days after randomization. A follow-up visit, either in person or via telephone, will be conducted 90 days after randomization to assess the mRS and EQ-5D-5L scores.
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;
- •Clinically diagnosed with ischemic cerebral infarction;
- •GCS score: 3-12;
- •Time from symptom onset to randomization ≤ 24 hours, including wake-up stroke or stroke without a witness; the time of symptom onset is defined as the "last known well time";
- •Pre-stroke mRS score of 0-1;
- •Head CT excludes intracranial hemorrhage or other non-ischemic pathologies;
- •The participant or legally authorized representative is capable of providing informed consent.
排除标准
- •Use of in BCS within 24 hours before treatment;
- •Known pregnancy or breastfeeding, or positive pregnancy test before randomization;
- •Allergy to BCS;
- •Impaired consciousness caused by other diseases, such as metabolic disorders (e.g., ketoacidosis), trauma, infectious diseases (e.g., pneumonia), neoplastic diseases (e.g., glioma), or toxic conditions (e.g., organophosphate poisoning);
- •Requiring or undergoing hemodialysis or peritoneal dialysis; known severe renal insufficiency (glomerular filtration rate <30 mL/min or serum creatinine >220 μmol/L);
- •Expected survival time less than 6 months (e.g., due to malignancy, severe cardiopulmonary disease, etc.);
- •Participation in other interventional clinical studies that may affect outcome assessment;
- •Other conditions deemed by the investigator to make the patient unsuitable for participation or pose significant risks (e.g., inability to understand and/or comply with study procedures and/or follow-up due to mental illness, cognitive or emotional disorders).
研究组 & 干预措施
Bovis Calculus Stativus (BCS) group
Patients with acute ischemic stroke accompanied by impaired consciousness within 72 hours and a Glasgow Coma Scale (GCS) score of 3-12, who are randomized to the experimental group, will be administered 0.6 g of BCS orally or via nasogastric tube immediately after recruitment. Subsequently, in accordance with guidelines, they will receive standard acute stroke treatment along with 0.6 g of BCS twice daily (bid) orally or via nasogastric tube for 5 consecutive days.
干预措施: Bovis Calculus Stativus (BCS) (Drug)
placebo group
Patients with acute ischemic stroke accompanied by impaired consciousness within 72 hours and a GCS score of 3-12, who are randomized to the control group, will be administered a placebo following the same regimen after recruitment. Subsequently, in accordance with guidelines, they will receive standard acute stroke treatment along with the placebo administered orally or via nasogastric tube for 5 consecutive days.
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of patients with GCS improvement ≥2 points
时间窗: Day 8 after randomization
Proportion of patients with a GCS score increase of 2 points or more to assess the improvement rate of impaired consciousness
次要结局
- GCS shift analysis(Day 8 after randomization)
- Proportion of mRS 0-2(Day 90 after randomization)
- Proportion of NIHSS score 0-1 or a reduction of ≥4 points from baseline(Day 8 after randomization)
- EQ-5D-5L index score(Day 90 after randomization)
- In-hospital stroke-associated pneumonia incidence rate(Day 8 after randomization)
研究者
Xiang Luo
Principal Investigator
Tongji Hospital