A prospective, multi-center, double-blind, randomized, placebo-controlled, parallel-group study to assess the efficacy and safety of clazosentan in reducing vasospasm-related morbidity and all-cause mortality in adult patients with aneurysmal subarachnoid hemorrhage treated by endovascular coiling. - CONSCIOUS 3
- Conditions
- Indication: Subarachnoid aneurysmal hemorrhageMedDRA version: 11Level: LLTClassification code 10042316Term: <Manually entered code. Term in E.1.1>
- Registration Number
- EUCTR2008-006785-29-FI
- Lead Sponsor
- Actelion Pharmaceuticals Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1470
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 >= 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.
* A successful procedure is defined as a procedure after which the end of procedure DSA indicates that the coiling was complete or adequate (i.e., more than 50% of the volume of the aneurysm is filled in by coiling material, investigator's assessment) and when the patient is not scheduled for a 2nd procedure on the ruptured aneurysm within 12 weeks post-aSAH.
†Patients must be evaluable for WFNS grade prior to the endovascular coiling procedure. Patients who cannot be assessed for WFNS post procedure due to a requirement for uninterrupted sedation (e.g., for high or unstable intracranial pressure [ICP]) may be included in the study provided that a CT scan is performed at least 12 hours post-procedure, but prior to randomization, ruling out any large procedure-related infarct.
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
1.Patients with subarachnoid hemorrhage (SAH) due to causes other than a saccular aneurysm (e.g., trauma or rupture of fusiform or mycotic aneurysms).
2.Patients with giant aneurysms (height or width >= 25 mm).
3.Patients with intraventricular or intracerebral blood, in the absence of subarachnoid blood, or with only a thin clot (short axis < 4 mm).
4.Presence of cerebral vasospasm seen on angiography (investigator’s assessment) prior to the endovascular coiling procedure. (Intraprocedural cerebral vasospasm is not an exclusion criterion).
5.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 post-procedure (e.g., hemiplegia or aphasia lasting >= 12 hours post-aneurysm coiling).*
6.Patients who have had their current ruptured aneurysm previously secured (successfully or not) by clipping.
7.Patients coiled with coiling material, which has not been approved by local health authorities.
8.Use of liquid embolism aneurysmal treatment or flow diverting device.
9.Patients with several aneurysms among which the ruptured one cannot be identified with certainty and which are not all secured during the coiling procedure.
10.Patients with no DSA at end-of-procedure.
11.Patients planned to have another securing procedure for any aneurysm after randomization and prior Week 12 post-aSAH.
12.Patients for whom study drug cannot be started within 56 hours after the aneurysm rupture.
13.Patients for whom it is known, at the time of screening, that certain follow-up, or protocol-mandated imaging assessments will not be feasible.
14.Patients with hypotension (systolic blood pressure (SBP) <= 90 mmHg) that is refractory to treatment.
15.Patients with aspiration pneumonia.
16.Patients with pulmonary edema or severe cardiac failure requiring inotropic support at the time of randomization.
17.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.
18.Significant kidney disease, as defined by plasma creatinine = 2.5 mg/dL (221 µmol/l)
and/or liver disease, as defined by total bilirubin > 2-fold the Upper Limit of Normal
(ULN) as measured at the local laboratory, and/or known diagnosis or clinical
suspicion of liver cirrhosis.
19.Patients receiving i.v. nimodipine or i.v. nicardipine must have these drugs discontinued at least 4 hours prior to initiation of the study treatment.
20.Patients who have received i.v. fasudil within the 24-hour period immediately preceding the planned start of study drug initiation.
21.Patients starting statins less than 2 weeks prior to admission must have them discontinued prior to study drug initiation.
22.Patients receiving 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.Patients who have received an investigational product including investigational coil material within 28 days prior to randomi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method