This study will evaluate if clazosentan (on top of normal routine medical care) can reduce the risk of developing complications related to cerebral vasospasm and permanent brain damage as compared to normal routine medical care alone.
When a blood vessel just outside the brain bursts and causes bleeding onto its surface, the space surrounding the brain (the subarachnoid space) fills with blood. This condition is called subarachnoid hemorrhage. The bleeding due to the rupture of a pouch-like structure or a bulge (called an aneurysm) that formed on one of the blood vessels is condition called aneurysmal subarachnoid hemorrhage (aSAH). In this study, clazosentan is being tested against normal routine medical care to determine if clazosentan can reduce the risk of developing complications related to vasospasm and permanent brain damage. Participation will last for approximately 6 months from the episode of bleeding. For subjects randomized in the high-risk prevention group, treatment will start within 96 hours following the time of the aneurysm rupture, and be administered where possible, for 14 days. For subjects randomized in the early treatment group, treatment must begin within 24 hours of the time of the angiogram documenting the cerebral vasospasm necessary for entry into the study. Treatment will be administered for a minimum of 6 days and a maximum of 14 days. Recruitment in the early treatment group has been discontinued. The end-of-study will be conducted as a telephone interview 6 months after the episode of bleeding.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
409
Clazosentan will be administered as a continuous intravenous infusion at the dose of 15 mg/hour for up to 14 days.
Placebo will be administered at the same infusion rate as clazosentan for up to 14 days.
Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation
Clinical deterioration due to delayed cerebral ischemia is defined as a worsening of at least 2 points compared to the reference score, on the modified Glasgow Coma Scale or the abbreviated National Institutes of Health Stroke Scale (aNIHSS), lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the Clinical Event Committee (CEC) based on a written charter and review of clinical data, case narratives, angiograms and Computed Tomography scans.
Time frame: Up to 14 days post-study drug initiation
Occurrence of Clinically Relevant Cerebral Infarction at Day 16 Post-study Drug Initiation
A clinical relevant cerebral infarction was defined as: all-cause cerebral infraction greater than or equal to 5 cm\^3 or cerebral infarction less than 5 cm\^3 in participants with clinical deterioration due to delayed cerebral ischemia. Cerebral infarction refers to new or worsened infarcts and was determined by a central radiology review comparing the total volume of infarcts on the computed tomography (CT) scan performed 16 days after study drug initiation with the total volume on the CT scan performed just prior to randomization.
Time frame: At Day 16 post study drug initiation
Long-term Clinical Outcome Assessed by the Modified Rankin Scale (mRS) at Week 12 Post-aneurysmal Subarachnoid Hemorrhage (aSAH)
The modified Rankin Scale (mRS) was used to measure the degree of disability in participants who had a ruptured saccular aneurysm and were at a high risk of developing a delayed cerebral infarction (DCI). The mRS is scored by the physician. The mRS scores ranged from 0 (no symptoms) to 6 (dead). The mRS score was dichotomized into poor outcome (score greater and equal to 3) and good outcome (score less than 3).
Time frame: At Week 12 post-aneurysmal subarachnoid hemorrhage (aSAH)
Long-term Clinical Outcome Assessed by the Glasgow Outcome Scale Extended (GOSE) at Week 12 Post-aSAH
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Stanford Hospital & Clinics - Stanford School of Medicine Dept. of Neurosurgery
Stanford, California, United States
Mayo clinic, Dept of Neurosurgery
Jacksonville, Florida, United States
University of Illinois - Department of Neurosurgery
Chicago, Illinois, United States
University of Maryland Medical Systems - Neurosurgery
Baltimore, Maryland, United States
Boston University School of Medicine / Boston University Medical Center
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center Dept of Neurosurgery
Boston, Massachusetts, United States
Northwell Health, Department of Neurosurgery
Manhasset, New York, United States
Mt Sinai Hospital
New York, New York, United States
Columbia University Medical Center Dept. of Neurology - Neurological Intensive Care Unit
New York, New York, United States
University Hospitals Case Medical Center - Department of Neurosurgery
Cleveland, Ohio, United States
...and 70 more locations
The Glasgow Outcome Scale - Extended (GOSE) is a scale scored by the physician. The GOSE scores range from 1 (dead) to 8 (upper good recovery). The long-term clinical outcome assessed by the GOSE was dichotomized into poor outcome (score ≤ 4) and good outcome (score \> 4)
Time frame: At Week 12 post-aneurysmal subarachnoid hemorrhage (aSAH)