Clinical Research Study With Clazosentan to Evaluate Its Effects on Preventing Complications Due to the Narrowing of the Blood Vessels (Vasospasm) in the Brain, Caused by Bleeding Onto the Surface of the Brain

Inclusion Criteria

• Written informed consent to participate in the study must be obtained from the subject or proxy/legal representative at any time from hospital admission to prior to initiation of any study-mandated procedure,
• Males and females aged 18 to 70 years (inclusive, at hospital admission),
• Participants with a ruptured saccular aneurysm, angiographically confirmed by DSA or CTA, which has been successfully secured within 72 hours of rupture, by surgical clipping or endovascular coiling,
• WFNS (World Federation of Neurosurgical Societies) grades 1-4 (based on Glasgow Coma Scale [GCS]) assessed after recovery from the aneurysm-securing procedure and after external ventricular drainage for hydrocephalus, if required.
• Participants must meet the criteria for the high-risk prevention group: Subjects with a "thick and diffuse clot" (thick and diffuse is defined as a thick confluent clot, more than 4 mm in thickness, involving 3 or more basal cisterns) on the hospital admission CT scan, absence of cerebral vasospasm at the time of randomization, and possibility to start study drug in the ICU (or equivalent environment where all protocol assessments can be performed and the Patient Management Guidelines followed), within 96 hours after the time of the aneurysm rupture.
• The recruitment into the early treatment group, i.e. participants without a thick and diffuse clot on the hospital admission CT scan who develop asymptomatic or minimally symptomatic moderate to severe angiographic vasospasm, within the 14-day period post-aneurysm rupture, and for whom it is possible to start study drug in the ICU (or equivalent environment where all protocol assessments can be performed and the Patient Management Guidelines followed), within 24 hours of this angiographic diagnosis, has been discontinued.
• Presence of a cerebral CT scan performed at least 8 hours post aneurysm securing procedure and within 24 hours prior to randomization.
• Absence of a significant (e.g., symptomatic or large) new or worsened cerebral infarct or re-bleeding of the repaired aneurysm on the post-procedure CT scan.
• A woman of childbearing potential is eligible only if the pregnancy test performed during the screening period is negative. Agreement must be obtained to take the necessary precautions to avoid pregnancy from hospital discharge until 30 days post-study drug discontinuation. If breastfeeding, agreement must be obtained to refrain for the duration of the treatment with study drug and until 30 days post-study drug discontinuation.
• Males are eligible for study participation only if they agree to take the necessary precautions to avoid pregnancy in a female partner from hospital discharge until 30 days post-study drug discontinuation.

Exclusion Criteria

• Aneurysmal subarachnoid hemorrhage (aSAH), aneurysm-securing procedure, vasospasm:
• Participants with SAH due to causes other than a saccular aneurysm (e.g., trauma or rupture of fusiform or mycotic aneurysms, SAH associated with arterio-venous malformation, vertebral dissections),
• Significant bleeding post aneurysm-securing procedure (e.g., due to intra-ventricular drain, intra-cerebral hemorrhage, epidural hematoma, vessel dissection or rupture, re-bleeding of the repaired aneurysm), based on investigator judgment,
• Intra-or peri-aneurysm securing procedure complication requiring non-routine medical or interventional treatment such as administration of an antithrombotic or anti-platelet agent (e.g., abciximab), which is not completely resolved prior to randomization,
• Intraventricular hemorrhage on the hospital admission CT scan, filling more than 50% of both lateral ventricles and with involvement of the 3rd and 4th ventricles.
• Intracerebral hemorrhage on the hospital admission CT scan, with an approximate volume of > 50 mL,
• Presence of cerebral vasospasm at hospital admission (initial admission or transfer from another hospital) believed to be associated with a prior bleed