Neurocritical Care

, Volume 13, Issue 3, pp 416–424

Preventing Vasospasm Improves Outcome After Aneurysmal Subarachnoid Hemorrhage: Rationale and Design of CONSCIOUS-2 and CONSCIOUS-3 Trials

Authors

    • Division of NeurosurgerySt. Michael’s Hospital, University of Toronto
  • Randall T. Higashida
    • Division of Neurointerventional RadiologyUniversity of California, San Francisco Medical Center
  • Emanuela Keller
    • Universitätsspital Zürich, Neurochirurgische Klinik
  • Stephan A. Mayer
    • Department of NeurologyColumbia University
  • Andy Molyneux
    • Nuffield Department of SurgeryJohn Radcliffe Hospital, University of Oxford
  • Andreas Raabe
    • Inselspital Bern, Universitätsklinik für Neurochirurgie
  • Peter Vajkoczy
    • Department of NeurosurgeryCharite Universitätsmedizin Berlin
  • Isabel Wanke
    • Clinic Hirslanden
  • Aline Frey
    • Actelion Pharmaceuticals Ltd
  • Angelina Marr
    • Actelion Pharmaceuticals Ltd
  • Sébastien Roux
    • Actelion Pharmaceuticals Ltd
  • Neal F. Kassell
    • Department of NeurosurgeryUniversity of Virginia
Taking a Closer Look at Trials

DOI: 10.1007/s12028-010-9433-3

Cite this article as:
Macdonald, R.L., Higashida, R.T., Keller, E. et al. Neurocrit Care (2010) 13: 416. doi:10.1007/s12028-010-9433-3

Abstract

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a frequent but unpredictable complication associated with poor outcome. Current vasospasm therapies are suboptimal; new therapies are needed. Clazosentan, an endothelin receptor antagonist, has shown promise in phase 2 studies, and two randomized, double-blind, placebo-controlled phase 3 trials (CONSCIOUS-2 and CONSCIOUS-3) are underway to further investigate its impact on vasospasm-related outcome after aSAH. Here, we describe the design of these studies, which was challenging with respect to defining endpoints and standardizing endpoint interpretation and patient care. Main inclusion criteria are: age 18–75 years; SAH due to ruptured saccular aneurysm secured by surgical clipping (CONSCIOUS-2) or endovascular coiling (CONSCIOUS-3); substantial subarachnoid clot; and World Federation of Neurosurgical Societies grades I–IV prior to aneurysm-securing procedure. In CONSCIOUS-2, patients are randomized 2:1 to clazosentan (5 mg/h) or placebo. In CONSCIOUS-3, patients are randomized 1:1:1 to clazosentan 5, 15 mg/h, or placebo. Treatment is initiated within 56 h of aSAH and continued until 14 days after aSAH. Primary endpoint is a composite of mortality and vasospasm-related morbidity within 6 weeks of aSAH (all-cause mortality, vasospasm-related new cerebral infarction, vasospasm-related delayed ischemic neurological deficit, neurological signs or symptoms in the presence of angiographic vasospasm leading to rescue therapy initiation). Main secondary endpoint is extended Glasgow Outcome Scale at week 12. A critical events committee assesses all data centrally to ensure consistency in interpretation, and patient management guidelines are used to standardize care. Results are expected at the end of 2010 and 2011 for CONSCIOUS-2 and CONSCIOUS-3, respectively.

Keywords

Aneurysmal subarachnoid hemorrhageCerebral vasospasmClazosentanCONSCIOUS studiesClinical outcome

Copyright information

© Springer Science+Business Media, LLC 2010