A Phase IIb, multi-center, international, double-blind, randomized, placebo-controlled, parallel-group, dose-finding study for the prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) by intravenous administration of clazosentan, a selective endothelin A (ETA) receptor antagonist.

Conditions: Prevention of ischaemic complications related to vasospasm in patients with aneurysmal subarachnoid haemorrhage

Registration Number: EUCTR2004-002453-31-DE

Lead Sponsor: Actelion Pharmaceuticals Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 400

Inclusion Criteria

1.Male or female patients aged 18 to 70 years (inclusive).

2.Patients with a ruptured saccular aneurysm that has been confirmed by digital subtraction angiography (DSA) and for which clipping or coiling (endovascular obliteration) is possible.

3.Patients with a diffuse or localized thick subarachnoid clot on baseline CT scan. Measurements defining clot thickness and extension are as follows:

Diffuse: Clot with long axis >= 20 mm, or any clot if present in both hemispheres
Localized: Clot with long axis < 20 mm
Thick: Clot with short axis >= 4 mm
Thin: Clot with short axis < 4 mm

4.Onset of aSAH clinical symptoms within the 48 hours preceding screening.

5.World Federation of Neurological Surgeons (WFNS) Grades I–IV, and those Grade V patients who improve to Grade IV or less after ventriculostomy.

6.In the case of multiple aneurysms, the aneurysm that has ruptured is identified with a high likelihood during the screening period.

7.Women of childbearing potential with pre-treatment negative serum pregnancy test.

8.Patient is able to start the study drug infusion within 56 hours after the rupture of the aneurysm, and the procedure option (clipping or coiling) must either be started within a maximum of 12 hours after the start of study drug infusion or should have been already performed.

9.Written informed consent to participate in the study must be obtained from the patient or a legal representative prior to initiation of any study-related procedure and enrollment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patients with SAH due to other causes (e.g., trauma or rupture of fusiform or mycotic aneurysms).

2.Patients with intraventricular or intracerebral blood, in the absence of subarachnoid blood.

3.No visualized clot or presence of only localized thin clot on CT (< 20 mm x 4 mm)

4.Presence of moderate (>=34 %) or severe cerebral vasospasm on screening angiogram.

5.Patients with hypotension (systolic blood pressure (SBP) <=90 mmHg) refractory to fluid therapy.

6.Patients with neurogenic pulmonary edema or severe cardiac failure requiring inotropic support.

7.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.

8.Advanced kidney and/or liver disease, as defined by plasma creatinine >=2 mg/dl (177 micromol/l) and/or total bilirubin > 3 mg/dl (51.3 micromol/l).

9.Any known or CT evidence of previous major cerebral damage (e.g., stroke [> 2 cm], traumatic brain injury [> 2 cm], previously treated cerebral aneurysm, arterial venous malformation [AVM]), or other preexisting cerebrovascular disorders, which may affect accurate diagnosis and evaluation of SAH.

10.Patients receiving prophylactic i.v. nimodipine or i.v. nicardipine. If present, these must be stopped at least 4 hours prior to initiation of the study treatment.

11.Patients who have received thrombolytics, including intracisternal administration, intrathecal treatments and therapeutic hypothermia for treatment of the SAH.

12.Patients who have received an investigational product within 28 days prior to randomization.

13.Patients with current alcohol or drug abuse or dependence.