CONSCIOUS 3 2010.

Trial name or title	Clazosentan in aneurysmal subarachnoid hemorrhage
Methods	Phase III clinical study
Participants	Inclusion criteria: 1. Males and females aged 18 to 75 years (inclusive). 2. Patients with a ruptured saccular aneurysm, confirmed by angiography, and which has been successfully secured by endovascular coiling. 3. 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. 4. Written informed consent Exclusion Criteria: 1. Patients with SAH due to causes other than a saccular aneurysm (e.g. trauma or rupture of fusiform or mycotic aneurysms). 2. Patients who experienced 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 postprocedure. 3. Patients who have had their current ruptured aneurysm previously secured (successfully or not) by clipping. 4. Patients coiled with coiling material, which has not been approved by local health authorities. 5. Use of liquid embolism aneurysmal treatment or flow diverting device. 6. Patients with several aneurysms among which the ruptured one cannot be identified with certainty and which are not all secured during the coiling procedure. 7. Patients with no DSA at end of procedure. 8. Patients planned to have another securing procedure for any aneurysm after randomization and prior week 12 post aSAH. 9. Patients for whom study drug cannot be started within 56 hours after the aneurysm rupture. 10. Patients for whom it is known, at the time of screening, that certain follow‐up, or protocol‐mandated imaging assessments will not be feasible. 11. Patients with hypotension (systolic blood pressure ≤ 90 mmHg) that is refractory to treatment. 12. Patients with aspiration pneumonia. 13. Patients with pulmonary edema or severe cardiac failure requiring inotropic support at the time of randomization. 14. Any severe or unstable concomitant condition or disease (e.g. known significant neurological deficit, cancer, hematological, or coronary disease), or chronic condition (e.g. psychiatric disorder), which, in the opinion of the investigator, would affect the assessment of the safety or efficacy of the study drug. 15. Significant kidney or liver disease, or both. 16. Patients receiving iv nimodipine or iv nicardipine must have these drugs discontinued at least 4 hours prior to initiation of the study treatment. 17. Patients who have received iv fasudil within the 24‐hour period immediately preceding the planned start of study drug initiation. 18. Patients starting statins less than 2 weeks prior to admission must have them discontinued prior to study drug initiation. 19. Patients receiving cyclosporine 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. 20. Patients who have received an investigational product including investigational coil material within 28 days prior to randomization or those who have already participated in the current study. 21. Patients unlikely to comply with the protocol (e.g. unable to return for follow‐up visits). 22. Known hypersensitivity to other endothelin receptor antagonists. 23. Patients with current alcohol or drug abuse or dependence
Interventions	Clazosentan (5 mg/hour) versus clazosentan (15 mg/hour) versus placebo
Outcomes	Cerebral vasospasm‐related morbidity and mortality of all‐causes; Glasgow Outcome Scale Extended at week 12 post‐aSAH, dichotomized into good (score > 4) and poor (score ≤ 4) outcome
Starting date	July 2009
Contact information	Alexa Richie (richie.alexa@mayo.edu)
Notes	‐

aSAH: aneurysmal subarachnoid hemorrhage 
 DSA: digital subtraction catheter angiography 
 iv: intravenous 
 SAH: subarachnoid hemorrhage