A Prospective, Multi-center, Open-label, Single-arm, Phase 2 Study to Assess the Efficacy and Safety of Clazosentan in Reversing Angiographically-confirmed Cerebral Vasospasm in Adult Subjects With Aneurysmal Subarachnoid Hemorrhage (aSAH) Treated by Surgical Clipping or Endovascular Coiling
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 11
- 主要终点
- Successful reversal of global cerebral vasospasm 3 hours post-study drug initiation
研究概览
简要总结
The purpose of this study is to evaluate the safety and potential therapeutic benefit of use of clazosentan in reversing cerebral vasospasm (a narrowing of blood vessels in the brain due to the presence of blood in the space around the brain) in patients who have suffered a condition known as aneurysmal subarachnoid hemorrhage caused by bleeding onto the surface of the brain from a ruptured brain aneurysm
详细描述
Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by bleeding onto the brain surface due to a rupture of a pouch or bulge in a brain vessel (called an aneurysm). It is a rare but serious condition with a high risk of death. Even patients who have had successful repair of the aneurysm remain at risk for developing cerebral vasospasm, which can result in harmful conditions related to the lack of oxygen to parts of the brain and death. Cerebral vasospasm usually occurs within the first couple of weeks after aSAH, and it is difficult to treat. Currently there is no safe, efficacious and widely available treatment. Previous animal studies have shown that a new drug under investigation, clazosentan, was able to reverse cerebral vasospasm in animal models of SAH. A first trial conducted in a small number of patients showed some benefit of clazosentan in reversing established cerebral vasospasm after aSAH. Clazosentan has already been evaluated in the prevention of cerebral vasospasm in several large clinical trials in aSAH. This current study aims to evaluate if clazosentan is effective and safe in the treatment of cerebral vasospasm after aSAH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent from the subject or proxy/legal representative
- •Aneurysmal subarachnoid hemorrhage (aSAH)confirmed by digital subtraction angiogram (DSA) or computed tomography angiogram (CTA), successfully secured by surgical clipping or endovascular coiling within 72 hours of rupture
- •World Federation of Neurological Surgeons (WFNS) grade 1-4 at admission, and which must not increase to grade 5 at the time of enrollment
- •Moderate or severe global cerebral vasospasm at the time of enrollment, documented by digital subtraction angiography (DSA) performed not earlier than 48 hours post aneurysm-securing procedure
- •Women of childbearing potential must have a negative serum pregnancy test at screening and must use a reliable method of contraception from hospital discharge up to 30 days after discontinuation of study drug infusion, and fertile males must use a condom as a contraceptive method during this same period
排除标准
- •SAH due to causes other than a saccular aneurysm
- •Any moderate or severe cerebral vasospasm on angiography prior to the aneurysm-securing procedure
- •Presence of a new or worsened cerebral infarct or evidence of significant bleeding post aneurysm-securing procedure, or re-bleeding, on a CT scan performed within 24 hours prior to enrollment
- •Total bilirubin > 2 times the upper limit of normal, and / or a known diagnosis or clinical suspicion of liver cirrhosis or moderate to severe hepatic impairment
- •Any severe or unstable concomitant condition or disease (e.g., cancer, hematological, or coronary disease) or chronic condition (e.g., drug abuse, severe alcoholism), which, in the opinion of the investigator, would interfere with the assessment of the safety or effect of the study treatment
研究组 & 干预措施
Clazosentan
Diluted solution administered as a continuous intravenous infusion at a rate of 15 mg/h for up to a cumulative maximum of 10 days
干预措施: Clazosentan (Drug)
结局指标
主要结局
Successful reversal of global cerebral vasospasm 3 hours post-study drug initiation
时间窗: 3 hours post-study drug initiation
Successful reversal is defined as an improvement in at least one level of severity on the "global vasospasm assessment" (i.e., from severe to moderate, mild, or none, or from moderate to mild or none), evaluated on Digital subtraction angiogram (DSA)
次要结局
- Successful reversal of global cerebral vasospasm 24 hours post-study drug initiation(24 hours post-study drug initiation)
- Maximum change from baseline in angiographic cerebral circulation time (CCT)(At baseline, 3 hours and 24 hours post-study drug initiation)
- Number of subjects with adverse events(Up to 30 days after study drug discontinuation)