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Clazosentan in Aneurysmal Subarachnoid Hemorrhage (CONSCIOUS-3)

This study has been terminated.
(Lack of efficacy data from the Phase 3 clinical study (AC-054-301; CONSCIOUS-2))
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT00940095
First received: July 13, 2009
Last updated: March 9, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Aneurysmal Subarachnoid Hemorrhage
Drug: Clazosentan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Cerebral vasospasm-related morbidity and mortality of all-causes as defined by the protocol [ Time Frame: Within 6 weeks post-aSAH ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Glasgow Outcome Scale Extended (GOSE) at Week 12 post-aSAH, dichotomized into good (score > 4) and poor (score ≤ 4) outcome. [ Time Frame: Week 12 post-aSAH ] [ Designated as safety issue: Yes ]

Enrollment: 577
Study Start Date: July 2009
Estimated Study Completion Date: April 2012
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clazosentan, 5mg/h Drug: Clazosentan
5 mg/h
Other Name: AXV-034343
Experimental: Clazosentan 15mg/h Drug: Clazosentan
15 mg/h
Other Name: AXV-034343
Placebo Comparator: Placebo Drug: Placebo
Matching Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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])(1)
  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.

      1. 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.

Exclusion Criteria :

  1. subarachnoid hemorrhage (SAH) due to causes other than saccular aneurysm.
  2. giant aneurysms (height or width > or = 25 mm).
  3. intraventricular or intracerebral blood, in absence of subarachnoid blood, or clot is only thin (short axis < 4 mm).
  4. cerebral vasospasm on angiography (investigator's assessment) prior to endovascular coiling (intraprocedural cerebral vasospasm is not an exclusion criterion).
  5. 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)*.
  6. current ruptured aneurysm previously secured (successfully or not) by clipping.
  7. coiling material used, which has not been approved by local health authorities.
  8. use of liquid embolism aneurysmal treatment or flow diverting device.
  9. several aneurysms among which the ruptured one cannot be identified with certainty and which are not all secured during the coiling procedure.
  10. no end-of-procedure DSA.
  11. another securing procedure planned for any aneurysm between randomization and Week 12 post-aSAH.
  12. study drug start >56 hours after the aneurysm rupture.
  13. known, at time of screening, that certain follow-up, or protocol-mandated imaging assessments will not be feasible.
  14. hypotension (systolic blood pressure < or = 90 mmHg) refractory to treatment.
  15. aspiration pneumonia.
  16. pulmonary edema or severe cardiac failure requiring inotropic support at time of randomization.
  17. 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).
  18. 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.
  19. infusion of i.v. nimodipine or i.v. nicardipine must have these drugs discontinued at least 4 hours prior to initiation of study treatment.
  20. infusion of i.v. fasudil within 24-hour period preceding planned start of study drug initiation.
  21. start of statins less than 2 weeks prior to admission must have them discontinued prior to study drug initiation.
  22. 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.
  23. 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).
  24. unlikely event to comply with protocol (e.g., unable to return for follow-up visits).
  25. known hypersensitivity to other endothelin receptor antagonists.26.current alcohol or drug abuse/dependence.

    • "Large territorial infarct" refers to infarcts detected during the endovascular coiling procedure or immediately post-procedure (i.e., CT performed for suspicion of cerebral infarct or other complication). This does not imply having to wait 24-48 hours post-procedure to perform the protocol-mandated CT scan in order to randomize a patient. Evaluation for a new major neurological deficit post-procedure implies reversal of sedation and performance of a GCS examination (verbal scores in intubated patients may be extrapolated from the eye-opening and motor scores using predefined values). If a new major neurological deficit does not improve within 12 hours after the coiling procedure, the patient cannot be included.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00940095

  Show 145 Study Locations
Sponsors and Collaborators
Actelion
Investigators
Study Director: Sebastien Roux, MD Actelion
  More Information

No publications provided by Actelion

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00940095     History of Changes
Other Study ID Numbers: AC-054-302
Study First Received: July 13, 2009
Last Updated: March 9, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
Aneurysmal
Subarachnoid
Hemorrhage
vasospasm
clazosentan
PIVLAZ
Actelion
surgical clipping

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

ClinicalTrials.gov processed this record on November 27, 2014