Clazosentan in Aneurysmal Subarachnoid Hemorrhage

Inclusion Criteria :

1. Males and females aged 18 to 75 years (inclusive).

2. Patients with a ruptured saccular aneurysm, confirmed by angiography (digital
subtraction angiography [DSA] or computed tomography angiography [CTA], investigator's
assessment), and which has been successfully* secured by endovascular coiling. The
time of aneurysm rupture must be known or possible to estimate with a reasonable
degree of certainty.

3. World Federation of Neurological Surgeons (WFNS) grade I-IV measured prior to the
endovascular coiling procedure, and which does not worsen to grade V post-procedure
(based on regular Glasgow Coma Scale [GCS])

4. Patients with any thick clot (short axis > or = 4 mm) on baseline CT scan
(investigator's assessment).

5. Women of childbearing potential must have a negative serum pregnancy test and must use
a reliable method of contraception during the 12 weeks following study drug
discontinuation.

6. Written informed consent to participate in the study must be obtained from the patient
or a legal representative prior to initiation of any study-mandated procedure and
randomization.

Exclusion Criteria :

1. Subarachnoid hemorrhage (SAH) due to causes other than saccular aneurysm.

2. Giant aneurysms (height or width > or = 25 mm).

3. Intraventricular or intracerebral blood, in absence of subarachnoid blood, or or with
only a thin clot (short axis < 4 mm)

4. Cerebral vasospasm on angiography (investigator's assessment) prior to endovascular
coiling (intraprocedural cerebral vasospasm is not an exclusion criterion).

5. A major complication during the endovascular coiling procedure, such as massive
intracranial bleeding, intracranial thromboembolism, coil migration, aneurysm
perforation or rupture, arterial dissection, major arterial occlusion, a large
territorial cerebral infarct defined as involving > 1/3 of a vascular territory, or a
new major neurological deficit post-procedure (e.g., hemiplegia or aphasia lasting >
or = 12 hours post-aneurysm coiling)*.

6. Current ruptured aneurysm previously secured (successfully or not) by clipping.

7. Coiling material used, which has not been approved by local health authorities.

8. Use of liquid embolism aneurysmal treatment or flow diverting device.

9. Several aneurysms among which the ruptured one cannot be identified with certainty and
which are not all secured during the coiling procedure.

10. No end-of-procedure DSA.

11. Another securing procedure planned for any aneurysm between randomization and Week 12
post-aSAH.

12. Study drug start >56 hours after the aneurysm rupture.

13. Known, at time of screening, that certain follow-up, or protocol-mandated imaging
assessments will not be feasible.

14. Hypotension (systolic blood pressure < or = 90 mmHg) refractory to treatment.

15. Aspiration pneumonia.

16. Pulmonary edema or severe cardiac failure requiring inotropic support at time of
randomization.

17. Any severe or unstable concomitant condition or disease (e.g., known significant
neurological deficit, cancer, hematological, coronary disease, psychiatric disorder),
which would affect assessment of the safety or efficacy of the study drug
(investigator's opinion).

18. Significant kidney disease defined by plasma creatinine > or = 2.5 mg/dL (221
micromol/l) and/or liver disease defined by total bilirubin > 2-fold Upper Limit of
Normal as measured at local laboratory, and/or known diagnosis or clinical suspicion
of liver cirrhosis.

19. Infusion of i.v. nimodipine or i.v. nicardipine must have these drugs discontinued at
least 4 hours prior to initiation of study treatment.

20. Infusion of i.v. fasudil within 24-hour period preceding planned start of study drug
initiation.

21. Start of statins less than 2 weeks prior to admission must have them discontinued
prior to study drug initiation.

22. Infusion of cyclosporin A or other calcineurin inhibitors (e.g., tacrolimus), or
patients for whom it is known at the time of randomization that these medications will
be started during the study drug infusion period.

23. Intake of an investigational product including investigational coil material within 28
days prior to randomization or those who have already participated in current study or
CONSCIOUS-2 (AC-054-301).

24. Unlikely event to comply with protocol (e.g., unable to return for follow-up visits).

25. Known hypersensitivity to other endothelin receptor antagonists.26.current alcohol or
drug abuse/dependence.

- "Large territorial infarct" refers to infarcts detected during the endovascular
coiling procedure or immediately post-procedure (i.e., CT performed for suspicion
of cerebral infarct or other complication). This does not imply having to wait
24-48 hours post-procedure to perform the protocol-mandated CT scan in order to
randomize a patient. Evaluation for a new major neurological deficit
post-procedure implies reversal of sedation and performance of a GCS examination
(verbal scores in intubated patients may be extrapolated from the eye-opening and
motor scores using predefined values). If a new major neurological deficit does
not improve within 12 hours after the coiling procedure, the patient cannot be
included.