The aim of this study is to demonstrate that clazosentan, administered as a continuous intravenous infusion at 5 mg/h until Day 14 post aneurysmal subarachnoid hemorrhage (aSAH), reduces the incidence of cerebral vasospasm -related morbidity and all-cause mortality within 6 weeks post-aSAH treated by surgical clipping. The primary endpoint of the study is the occurrence of cerebral vasospasm-related morbidity, and mortality of all-causes within 6 weeks post-aSAH, defined by at least one of the following: 1. Death (all causes). 2. New cerebral infarct(s) due to cerebral vasospasm as either the primary or relevant contributing cause, or not adjudicated to be entirely due to causes other than vasospasm. 3. Delayed ischemic neurological deficit (DIND) due to cerebral vasospasm as either the primary or relevant contributing cause, or not adjudicated to be entirely due to causes other than vasospasm. 4. Neurological signs or symptoms (depending on state of consciousness), in the presence of confirmed cerebral vasospasm on angiography (DSA or CTA), leading to the administration of a valid rescue therapy. An independent Critical Events Committee (CEC) will adjudicate whether or not patients meet the primary endpoint and its individual morbidity components.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,157
Intravenous clazosentan administered by continuous infusion at 5 mg/h
Placebo administered by continuous infusion matching clazosentan administration
Barrow Neurosurgical Associates
Phoenix, Arizona, United States
Colorado Neurological Institute
Englewood, Colorado, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Columbia University Medical Center
New York, New York, United States
State University of New York at Stony Brook-Health Sciences Center
Stony Brook, New York, United States
Cerebral vasospasm-related morbidity and mortality of all-causes as defined by the protocol
Time frame: Within 6 weeks post-aSAH
Glasgow Outcome Scale Extended (GOSE) at Week 12 post-aSAH, dichotomized into good (score > 4) and poor (score ≤ 4) outcome.
Time frame: Week 12 post-aSAH
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University of Cincinnati-Department of Neurosurgery
Cincinnati, Ohio, United States
University Hospitals Case Medical Center-Department of Neurosurgery
Cleveland, Ohio, United States
Oregon Health & Science University-Oregon Stroke Center
Portland, Oregon, United States
Thomas Jefferson University School of Medicine-Jefferson Hospital for Neuroscience
Philadelphia, Pennsylvania, United States
University of Virginia Health System-Department of Neurosurgery
Charlottesville, Virginia, United States
...and 107 more locations