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Clazosentan in Preventing the Occurrence of Cerebral Vasospasm Following an Aneurysmal Subarachnoid Hemorrhage (aSAH) (CONSCIOUS-1)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00111085
First Posted: May 18, 2005
Last Update Posted: October 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Actelion
  Purpose
The purpose of the study is to measure how effective and safe three different doses of the drug clazosentan are in preventing vasospasm after subarachnoid hemorrhage.

Condition Intervention Phase
Aneurysmal Subarachnoid Hemorrhage Drug: Clazosentan 1 mg/h Drug: Clazosentan 5 mg/h Drug: Clazosentan 15 mg/h Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Occurrence of moderate or severe cerebral vasospasm, as measured by cerebral angiography [ Time Frame: Up to day 14 ]
    If the patient develops clinical or sonographic changes suggestive of vasospasm prior to or after Day 9 ± 2 and until Day 14 post-aneurysm rupture, an angiogram will be performed to confirm the vasospasm. If vasospasm is documented prior to Day 9 ± 2, the Day 9 ± 2 angiogram is no longer required. In the case that a patient only develops clinical symptoms suggestive of vasospasm later than Day 9 ± 2 and up to Day 14, an additional angiogram should be performed to confirm the diagnosis of vasospasm. If the latter shows a higher grade of vasospasm than the previous one, it will be used for comparison to the baseline angiogram for evaluation of the primary endpoint.


Secondary Outcome Measures:
  • Occurrence of vasospasm-related morbidity, and mortality of all causes defined as the occurrence of death of any cause within the first 6 weeks post-aneurysm rupture OR [ Time Frame: Within 6 weeks ]
  • Occurrence of vasospasm-related morbidity, and mortality of all causes defined as the occurence of new cerebral infarct within first 6 weeks post-aneurysm rupture based on local investigator reading of post-baseline CT scans OR [ Time Frame: Within 6 weeks ]
  • Occurrence of vasospasm-related morbidity, and mortality of all causes defined as the occurence of delayed ischemic neurological deficits (DIND) due to vasospasm (based on investigator assessments) within 14 days post-aneurysm rupture OR [ Time Frame: Within 14 days ]
  • Occurrence of vasospasm-related morbidity, and mortality of all causes defined as occurrence of use of rescue medication due to vasospasm within 14 days post-aneurysm rupture [ Time Frame: Within 14 days ]
  • Clinical outcome at 12 weeks post-aneurysm rupture as measured by the Modified Rankin Scale (mRS) score [ Time Frame: At 12 weeks ]
  • Clinical outcome at 12 weeks post-aneurysm rupture as measured bythe Glasgow Outcome Scale - Extended Version (GOSE) score [ Time Frame: At 12 weeks ]

Enrollment: 413
Actual Study Start Date: January 10, 2005
Study Completion Date: March 30, 2006
Primary Completion Date: March 30, 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clazosentan 1 mg/h
intravenous clazosentan at 1 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Drug: Clazosentan 1 mg/h
Subjects receive intravenous clazosentan at a rate of 1 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Other Name: ACT-108475
Experimental: Clazosentan 5 mg/h
intravenous clazosentan at 5 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Drug: Clazosentan 5 mg/h
Subjects receive intravenous clazosentan at a rate of 5 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Other Name: ACT-108475
Experimental: Clazosentan 15 mg/h
intravenous clazosentan at of 15 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Drug: Clazosentan 15 mg/h
Subjects receive intravenous clazosentan at a rate of 15 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Other Name: ACT-108475
Placebo Comparator: Placebo
intravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Drug: Placebo
Subjects receive intravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Male or 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
  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. Start of screening within 48 hours post onset of aSAH clinical symptoms
  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

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 any degree of 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00111085


Locations
United States, Illinois
Dr. Giuseppe Lanzino
Peoria, Illinois, United States
United States, Indiana
Dr. Horner
Indianapolis, Indiana, United States
United States, Maryland
Dr. Aldrich
Baltimore, Maryland, United States
United States, Massachusetts
Dr. Ogilvy
Boston, Massachusetts, United States
United States, Ohio
Dr. Zuccarello
Cincinnati, Ohio, United States
Dr. Woo
Cleveland, Ohio, United States
United States, Pennsylvania
Dr. Rosenwasser
Philadelphia, Pennsylvania, United States
Dr. Zager
Philadelphia, Pennsylvania, United States
United States, Texas
Dr. George A. Lopez
Houston, Texas, United States
United States, Virginia
Dr. Bullock
Richmond, Virginia, United States
Canada, Alberta
Dr. Wong
Calgary, Alberta, Canada
Dr. Findlay
Edmonton, Alberta, Canada
Canada, British Columbia
Dr. Redekop
Vancouver, British Columbia, Canada
Canada, Ontario
Dr. Ferguson
Toronto, Ontario, Canada
Canada, Quebec
Dr. Bojanowski
Montreal, Quebec, Canada
Canada
Dr. Fleetwood
Halifax, Nova Scotia, Canada
Sponsors and Collaborators
Actelion
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00111085     History of Changes
Other Study ID Numbers: AC-054-201
First Submitted: May 17, 2005
First Posted: May 18, 2005
Last Update Posted: October 30, 2017
Last Verified: October 2017

Keywords provided by Actelion:
delayed ischemic neurological deficits (DIND)
vasospasm
clazosentan
cerebral vasospasm
computer tomography scan (CT scan)
digital subtraction angiography (DSA)
endothelin A receptor
aneurysmal subarachnoid hemorrhage (aSAH)

Additional relevant MeSH terms:
Hemorrhage
Subarachnoid Hemorrhage
Vasospasm, Intracranial
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases