CONSCIOUS-1
Clazosentan in Preventing the Occurrence of Cerebral Vasospasm Following an Aneurysmal Subarachnoid Hemorrhage
|
Purpose:
To measure how effective and safe three different doses of the drug clazosentan are in preventing vasospasm after subarachnoid hemorrhage.
Interventions:
Clazosentan
Intravenous endothelin receptor antagonist.
|
Year Started:
2004
Year Finished:
2006
Design:
Prevention, Randomized, Double-Blind, Dose Comparison, Parallel Assignment, Safety/Efficacy Study, Interventional.
Inclusion Criteria
Female patients aged 18 to 70 years (inclusive) or male patients aged 45 to 70 (inclusive) or males aged 18 to 44 (inclusive) who are surgically or naturally sterile or can personally sign the core Informed Consent; 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; patients with a diffuse or localized thick subarachnoid clot on baseline CT scan; start of screening within 48 hours post onset of aSAH clinical symptoms; WFNS Grades I–IV, and those Grade V patients who improve to Grade IV or less after ventriculostomy.
Exclusion Criteria
Patients with SAH due to other causes (e.g., trauma or rupture of fusiform or mycotic aneurysms); patients with intraventricular or intracerebral blood, in the absence of subarachnoid blood; no visualized clot or presence of only localized thin clot on CT; presence of any degree of cerebral vasospasm on screening angiogram.
Patient Involvement:
Patient will receive IV drug clazosentan within 48 hours of aSAH. Will undergo digital subtraction angiography for diagnosis. Baseline CT scan and neurological testing with WFNS.
Primary Outcome:
To assess the efficacy of 3 dose levels (1 mg/h, 5 mg/h and 15 mg/h) of clazosentan in preventing the occurrence of cerebral vasospasm following aSAH.
Secondary Outcome:
To assess the ability of clazosentan to reduce the occurrence of early morbidity/mortality; to assess the effect of clazosentan on clinical outcome; to assess the safety and tolerability of three dose levels of clazosentan.
Results:
Moderate or severe vasospasm was reduced in a dose-dependent fashion from 66% in the placebo group to 23% in the 15 mg/h clazosentan group (risk reduction, 65%; 95% CI, 47% to 78%; P<0.0001). No significant effects were seen on secondary end points. Post hoc analysis using a centrally assessed morbidity/mortality end point that included death and rescue therapy but only cerebral infarcts and delayed ischemic neurological deficit due to vasospasm on central review showed a trend toward improvement with clazosentan (risk reduction, 37%, 28%, and 29% in the 1, 5, and 15 mg/h groups versus 39% in the placebo group, nonsignificant). Clazosentan was associated with increased rates of pulmonary complications, hypotension, and anemia. Clazosentan significantly decreased moderate and severe vasospasm in a dose-dependent manner and showed a trend for reduction in vasospasm-related morbidity/mortality in patients with aneurysmal subarachnoid hemorrhage when centrally assessed. Overall, the adverse effects were manageable and not considered serious.
Source of Information:
ClinicalTrials.gov.
|
|
Web Links and Publications:
|
|
This information last updated on: 11/3/2009
Reviewed on: 08/18/2009.
|
Trials
Directories