Clazosentan in Aneurysmal Subarachnoid Hemorrhage

Stopped early · Phase 3 · Has a placebo group

Conditions studied: Aneurysmal Subarachnoid Hemorrhage

In brief

The aim of this study is to demonstrate that clazosentan, administered as a continuous intravenous infusion at either 5 mg/h or 15 mg/h until Day 14 post aneurysmal subarachnoid hemorrhage (aSAH), reduces the incidence of cerebral vasospasm-related morbidity and all-cause mortality within 6 weeks post-aSAH treated by endovascular coiling. The primary endpoint of the study is 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. 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. 4. Administration of a valid rescue therapy in the presence of confirmed cerebral vasospasm on angiography (DSA or CTA). An independent Critical Events Committee (CEC) will adjudicate whether or not patients meet the primary endpoint and its individual morbidity components.

Key facts

Study ID

NCT00940095

Run by

Idorsia Pharmaceuticals Ltd.

People needed

577

Starts

2009-07-01

Expected to finish

2011-01-01

Last updated by the study team

2018-07-09

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Males and females aged 18 to 75 years (inclusive).
• 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.
• 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])
• Patients with any thick clot (short axis > or = 4 mm) on baseline CT scan (investigator's assessment).
• 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.
• 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.

You may not qualify if…

• Subarachnoid hemorrhage (SAH) due to causes other than saccular aneurysm.
• Giant aneurysms (height or width > or = 25 mm).
• Intraventricular or intracerebral blood, in absence of subarachnoid blood, or or with only a thin clot (short axis < 4 mm)
• Cerebral vasospasm on angiography (investigator's assessment) prior to endovascular coiling (intraprocedural cerebral vasospasm is not an exclusion criterion).
• 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 > or = 12 hours post-aneurysm coiling)*.
• Current ruptured aneurysm previously secured (successfully or not) by clipping.
• Coiling material used, which has not been approved by local health authorities.
• Use of liquid embolism aneurysmal treatment or flow diverting device.
• Several aneurysms among which the ruptured one cannot be identified with certainty and which are not all secured during the coiling procedure.
• No end-of-procedure DSA.
• Another securing procedure planned for any aneurysm between randomization and Week 12 post-aSAH.
• Study drug start >56 hours after the aneurysm rupture.
• Known, at time of screening, that certain follow-up, or protocol-mandated imaging assessments will not be feasible.
• Hypotension (systolic blood pressure < or = 90 mmHg) refractory to treatment.
• Aspiration pneumonia.
• Pulmonary edema or severe cardiac failure requiring inotropic support at time of randomization.
• Any severe or unstable concomitant condition or disease (e.g., known significant neurological deficit, cancer, hematological, coronary disease, psychiatric disorder), which would affect assessment of the safety or efficacy of the study drug (investigator's opinion).
• Significant kidney disease defined by plasma creatinine > or = 2.5 mg/dL (221 micromol/l) and/or liver disease defined by total bilirubin > 2-fold Upper Limit of Normal as measured at local laboratory, and/or known diagnosis or clinical suspicion of liver cirrhosis.
• Infusion of i.v. nimodipine or i.v. nicardipine must have these drugs discontinued at least 4 hours prior to initiation of study treatment.
• Infusion of i.v. fasudil within 24-hour period preceding planned start of study drug initiation.
• Start of statins less than 2 weeks prior to admission must have them discontinued prior to study drug initiation.
• Infusion of 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.
• Intake of an investigational product including investigational coil material within 28 days prior to randomization or those who have already participated in current study or CONSCIOUS-2 (AC-054-301).
• Unlikely event to comply with protocol (e.g., unable to return for follow-up visits).
• Known hypersensitivity to other endothelin receptor antagonists.26.current alcohol or drug abuse/dependence.

Where it is running

• UCSF Medical Centre — San Francisco, California, United States
• Stanford Hospital and Clinis — Stanford, California, United States
• Colorado Neurological Institute — Englewood, Colorado, United States
• Yale Univerity School of Medicine — New Haven, Connecticut, United States
• University of South Florida — Tampa, Florida, United States
• Rush University Medical Center — Chicago, Illinois, United States
• University of Illnois — Chicago, Illinois, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Boston Medical Centre — Boston, Massachusetts, United States
• William Beaumont Hospital — Royal Oak, Michigan, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Barnes_Jewish Hospital — St Louis, Missouri, United States
• Capital Health System Inc. d/b/a The Stroke and Cerebrovascular Center of New Jersey — Trenton, New Jersey, United States
• Columbia University Medical Center — New York, New York, United States
• New York Presbyteruan Hospital - Weill Cornell Medical Centre — New York, New York, United States
• State University of New York at Stony Brook — Stony Brook, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States
• University of Cincinnati — Cincinnati, Ohio, United States
• University Hospitals Case Medical Center — Cleveland, Ohio, United States
• Oklahoma University Health Sciences Center — Oklahoma City, Oklahoma, United States
• Oregon Health & Science University — Portland, Oregon, United States
• Thomas Jefferson University School of Medicine — Philadelphia, Pennsylvania, United States
• Temple University Hospital — Philadelphia, Pennsylvania, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• Glendale Adventist Medical Center — Glendale, California, United States

Full record on ClinicalTrials.gov

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