Indication: Subarachnoid aneurysmal hemorrhage MedDRA version: 11 Level: LLT Classification code 10042316 Term:
Conditions
Interventions
Product Name: Clazosentan
Product Code: ACT-108475 or AXV-034343
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Clazosentan
CAS Number: 180384-56-9
Current Sponsor cod
Sponsors
Actelion Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
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 = 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. Informed consent to participate in the study must be obtained from the patient prior to initiation of any study-mandated procedure and randomization (for details please see Section 3.9.6.1). * 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
Exclusion criteria
Exclusion criteria: 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 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) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To demonstrate that at least one dose (5 or 15 mg/h) of clazosentan reduces the incidence of cerebral vasospasm related morbidity and all-cause mortality within 6 weeks post aneurysmal subarachnoid hemorrhage (aSAH) in patients treated by endovascular coiling.;Secondary Objective: •To demonstrate that at least one dose (5 or 15 mg/h) of clazosentan improves clinical outcome at Week 12 post-aSAH in patients treated by endovascular coiling, as measured by the dichotomized Glasgow Outcome Scale (extended version(GOSE)). •To evaluate the impact of clazosentan on total infarct volume at Week 6 post-aSAH in patients treated by endovascular coiling, and on each individual component of the primary endpoint. •To evaluate the safety and tolerability of clazosentan. ;Primary end point(s): The occurrence of cerebral vasospasm-related morbidity, and mortality of all causes within 6 weeks post-aSAH, defined by at least one of the following: 1.Death (all causes) 2.New cerebral infarct(s) due to cerebral vasospasm as either the primary or relevant contributing cause, or not adjudicated to be entirely due to causes other than vasospasm (e.g., lesions arising from intra-cerebral hemorrhage, the aneurysm endovascular coiling procedure, the primary injury, or ventricular drain encephalomalacia)* 3.Delayed ischemic neurological deficit (DIND) due to cerebral vasospasm as either the primary or relevant contributing cause, or not adjudicated to be entirely due to causes other than vasospasm (e.g., hydrocephalus, seizure, etc.)* 4.Administration of a valid rescue therapy in the presence of confirmed cerebral vasospasm on angiography (DSA or CTA)* (see detailed definition of this endpoint component and the list of qualifying rescue therapies in the study protocol, Section 3.8.1.1). *An independent Critical Events Committee (CEC) will adjudicate whether or not patients meet the primary endpoint and its individual morbidity components. It is expected that the incidence o | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Slovenia, Spain, Sweden
Outcome results
None listed