Safety and Effectiveness Study of Deferoxamine and Xingnaojing Injection in Intracerebral Hemorrhage
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Numbers of patients with the perihematomal edema (PHE) volume variation.
研究概览
简要总结
The main purpose of this study is to determine whether deferoxamine and xingnaojing injection is effective and safe as a treatment for intracerebral hemorrhage.
详细描述
Research shows that more than 1/3 of patients with acute cerebral hemorrhage in the first 24 hours will be expanding hematoma. The treatment of acute cerebral hemorrhage has two main targets: prevention of hematoma enlargement in primary brain damage; Reduce hematoma secondary brain damage caused by blood toxicity degradation products. At present, the curative effect of drug treatment of acute cerebral hemorrhage remains limited, using drug therapy to treat hematoma caused by blood toxicity degradation products secondary brain damage, is one of the main current international research direction and hotspot. Recent studies have found that iron overload in cells in acute cerebral hemorrhage stove weeks edema secondary lesion plays a very important role. Acute cerebral hemorrhage animal model research and small sample clinical study has shown that the iron chelator deferoxamine has good curative effect and security. Currently ongoing international HI-DEF test plans to assess the efficacy and safety of high-dose deferoxamine treatment within 24 h of patients with acute cerebral hemorrhage.
Basic research shows Xingnaojing injection can inhibit inflammatory reaction, scavenging free radicals, relieve acute cerebral hemorrhage hematoma surrounding edema and has a variety of brain protection mechanism. The current study builds on these results to assess the potential utility of deferoxamine and Xingnaojing injection as a therapeutic intervention in ICH.
This is a prospective, multi-center, double-blind, randomized, placebo-armed clinical study to test the safety and effectiveness of deferoxamine and Xingnaojing injection treatment in intracerebral hemorrhage. The investigators will randomize 180 subjects with ICH equally (1:1:1) to either DFO at 40mg/kg/day (up to a maximum daily dose of 6000 mg/day), or Xingnaojing injection, or saline placebo, given by continuous IV infusion for 5 consecutive days. Treatment will be initiated within 12 hours after ICH symptom onset.
The main objectives are:
- Examining the effects of DFO and Xingnaojing injection on peri-hematoma edema (PHE) volume progression between baseline and post-treatment CT/MRI scans and the residual cavity volume at 90 days.
- Obtaining data on the National Institute of Health Stroke Scale (NIHSS) to explore the effects of treatment on neurological functions.
- Examining the effects of DFO and Xingnaojing injection on biomarkers of acute cerebral hemorrhage such as ferritin, interleukin - 6, matrix metalloproteinase 9, tumor necrosis factor alpha and so on.
- Study the traditional Chinese medicine(TCM)curative effect evaluation of the roles of different treatment methods on secondary damage after ICH.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 and ≤ 80 years
- •The diagnosis of ICH is confirmed by brain CT scan
- •NIHSS score ≥ 6 and GCS > 6 upon presentation
- •The first dose of the study drug can be administered within 12h of ICH symptom onset
- •Functional independence prior to ICH, defined as pre-ICH mRS ≤ 1
- •Signed and dated informed consent is obtained.
排除标准
- •Known hypersensitivity to deferoxamine or xingnaojing injection
- •Known severe iron deficiency anemia (defined as hemoglobin concentration < 7g/dL or requiring blood transfusions)
- •Abnormal renal function, defined as serum creatinine > 2 mg/dL
- •Planned surgical evacuation of ICH prior to administration of study drug
- •Suspected secondary ICH related to tumour, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis
- •Infratentorial hemorrhage
- •Irreversibly impaired brainstem function (bilateral fixed and dilated pupils and extensor motor posturing)
- •Complete unconsciousness, defined as a score of 3 on item 1a of the NIHSS (Responds only with reflex motor or autonomic effects or totally unresponsive, and flaccid)
- •Pre-existing disability, defined as pre-ICH mRS ≥ 2
- •Coagulopathy - defined as elevated aPTT or INR >1.3 upon presentation; concurrent use of direct thrombin inhibitors (such as dabigatran), direct factor Xa inhibitors (such as rivaroxaban), or low-molecular-weight heparin
- •Taking iron supplements containing ≥ 325 mg of ferrous iron
- •Patients with heart failure taking > 500 mg of vitamin C daily
- •Known severe hearing loss
- •Known pregnancy, or positive pregnancy test, or breastfeeding
- •Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, noncompliance, living in another state or any other cause
- •Life expectancy of less than 90 days due to comorbid conditions
研究组 & 干预措施
Deferoxamine
Deferoxamine mesylate supplied in vials containing 500 mg of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water.
干预措施: deferoxamine (Drug)
Xingnaojing injection
Xingnaojing injection supplied in vials containing 20 ml liquid xingnaojing.
干预措施: Xingnaojing injection (Drug)
Normal Saline
0.9% sodium chloride
干预措施: Normal saline (Drug)
结局指标
主要结局
Numbers of patients with the perihematomal edema (PHE) volume variation.
时间窗: 7 days
decreases of more than 20% from initial PHE volumes were defined as "decreased" PHE volume; increases of more than 20% from initial PHE volumes were defined as "increased" PHE volume; changes between -20% and 20% were defined as "unchanged".
次要结局
- The residual cavity volume(90 days)
- The variation of the mRS score and the Bathel Index(90 days)
- mortality(90 days)
- Frequency of Treatment-related Adverse Events(90 days)
研究者
Maolin He
director of the Neurology department, Beijing Shijitan Hospital
Capital Medical University