We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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:
ClinicalTrials.gov Identifier:
NCT00940095
First Posted: July 15, 2009
Last Update Posted: May 15, 2015
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 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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 ]

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 ]

Enrollment: 577
Study Start Date: July 2009
Study Completion Date: January 2011
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

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 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
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): NCT00940095


  Hide Study Locations
Locations
United States, California
Glendale Adventist Medical Center
Glendale, California, United States, 91206
UCSF Medical Centre
San Francisco, California, United States, 94143
Stanford Hospital and Clinis
Stanford, California, United States, 94305-5327
United States, Colorado
Colorado Neurological Institute
Englewood, Colorado, United States, 80110
United States, Connecticut
Yale Univerity School of Medicine
New Haven, Connecticut, United States, 06510
United States, Florida
University of South Florida
Tampa, Florida, United States, 33606
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
University of Illnois
Chicago, Illinois, United States, 60612
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Boston Medical Centre
Boston, Massachusetts, United States, 02118
United States, Michigan
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Barnes_Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, New Jersey
Capital Health System Inc. d/b/a The Stroke and Cerebrovascular Center of New Jersey
Trenton, New Jersey, United States, 08638
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
New York Presbyteruan Hospital - Weill Cornell Medical Centre
New York, New York, United States, 10065
State University of New York at Stony Brook
Stony Brook, New York, United States, 11794-8122
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Oklahoma
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97219
United States, Pennsylvania
Thomas Jefferson University School of Medicine
Philadelphia, Pennsylvania, United States, 19107
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
United States, South Carolina
Medical University of South Carolina
Charlestown, South Carolina, United States, 29425
United States, Texas
University of Texas Southwestern Zale Lipshy Hospital
Dallas, Texas, United States, 75390
United States, Virginia
Univ. of VA Health System
Charlottesville, Virginia, United States, 22908
Virginia Commonwealth University Medical Centre
Richmond, Virginia, United States, 23284
Virginia Commonwealth University
Richmond, Virginia, United States, 980631
Argentina
Hospital Aleman
Buenos Aires, Argentina, C1118AAT
Clinica De Sol
Buenos Aires, Argentina, C1425DQI
ENERI
Buenos Aires, Argentina, C1426ENF
Australia, Queensland
Gold Coast Hospital
Southport, Queensland, Australia, 4215
Australia
Royal Brisbane & Women's Hosptal
Brisbane, Australia, QLD 4029
Royal Prince Alfred Hosptial
Camperdown, Australia, NSW 2050
Monash Medical Centre
Clayton, Australia, VIC 3168
Princess Alexandra Hospital
Wooloongabba, Australia, QLD 4102
Austria
Landeskrankenhaus und Medizinische Universitat
Graz, Austria, A-8036
Medizinsche Universitat Innsbruck
Innsbruck, Austria, 6020
University Fur Neurochirurgie, SALK, Christian Doppler Hospital
Salzburg, Austria, 5020
AKH University of Vienna, Medical Univ. Of Neurosurgery
Vienna, Austria, 1090
Belgium
UZ Antwerpen
Antwerp, Belgium, 2650
ULB Erasme
Brussels, Belgium, 1070
UZ Brussels
Brussels, Belgium, 1090
UCL Saint-Luc
Brussels, Belgium, 1200
UZ Brussels
Brussels, Belgium
UZ Gent
Gent, Belgium, 9000
UZ Gasthuisberg
Leuven, Belgium, 3000
Brazil
Hospital das Clinicas da UFMG
Belo Horizonte, Brazil, 30110-934
Hospital de Clinicas da Universidade Federal do Parana
Curitiba, Brazil, 80060-900
Clinica de Neurologia de
Joinville, Brazil, 89202-000
Hospital de Clínicas de Niteroí
Niteroí, Brazil, 24020-090
Hospital Moinhos de Vento
Porto Alegre, Brazil, 90035-001
Hospital Santa Marcelina
Sao Paulo, Brazil, 08270-070
Santa Case de Misericordia de Sobral
Sobral, Brazil, 62010-550
Canada, Alberta
University of Calgary - Foothills Medical Center
Calgary, Alberta, Canada, T2N 1M9
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
Vancouver Hospital & Health Sciences
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Nova Scotia
QEII Heath Sciences Center - Halifax Infirmary
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
Hamilton General Hospital
Toronto, Ontario, Canada, L8L 2X2
St. Michael's Hospital, University of Toronto
Toronto, Ontario, Canada, M5C 3G7
Canada, Quebec
CHUM Hospital - Notre Dame
Montreal, Quebec, Canada, H2L 4M1
Canada, Saskatchewan
Royal University Hospital
Saskatoon, Saskatchewan, Canada, S7N 0W8
Canada
Hopital de I'Enfant-Jesus
Quebec, Canada, G1J 1Z4
Chile
Hospital Regional de Concepción
Concepcion, Chile, 4070038
Institute de Neurocirugia
Santiago, Chile, 7500691
Hospital Clinico Pontificia Universidad Católica de Chile
Santiago, Chile, 8330024
Clinica Davila
Santiago, Chile, 8431657
Hospital Carlos Van Buren
Valparaiso, Chile, 2352499
Czech Republic
Fakultni nemocnice Bmo
Bmo, Czech Republic, 625 00
Nemocnice Ceske Budejovice
Ceske Budejovice, Czech Republic, 370 87
Fakultní nemocnice Ostrava
Ostrava, Czech Republic, 169 02
Fakultni nemocnice Ostrava
Ostrava, Czech Republic, 708 52
Nemocnice Na Homolce
Praha, Czech Republic, 150 30
ÚVN Praha
Praha, Czech Republic, 16902
Fakultni nemocnice Homoice
Praha, Czech Republic, 500 05
Masarykova nemocnice Usti n. Labem
Usti nad Labem, Czech Republic, 401 13
Denmark
The Neuroscience Center, Copenhagen University Hospital
Copenhagen, Denmark, 2100
Glostrup Hospital
Glostrup, Denmark, 2600
Odense University Hospital
Odense, Denmark, DK 5000
Finland
Helsinki University Central Hospital
Helsinki, Finland, Fin-00029 HUS
Tampere University Central Hospital (TAYS)
Tampere, Finland, 33520
France
CHU d'Angers
Angers Cedex 9, France, 49933
Hopital Pellegrin
Bordeaux cedex, France, 33076
Hopital neurologique et Neuro-Chirurgical Pierre Wertheimer
Bron, France, 69677
Hopital Henru Mondor
Creteil, France, 94010
Hopital General
Dijon, France, 21033
Hopital de la Timone - CHU de Marseille
Marseille cedex 5, France, 13385
Hopital Gui de Chauliac
Montpellier, France, 34295
Hopital central
Nancy, France, 54035
Germany
Universitatsklinikum Augsburg Clinic for Diagnostic Radiology and Neuroradiology
Augsburg, Germany, 86156
Charite Universitatsmedzin Berlin
Berlin, Germany, D-13353
Universitatsklinikum Bonn
Bonn, Germany, 53105
University of Bonn Medical Center
Bonn, Germany, 53105
Klinik imd Poliklinik fur Neurochirurgie
Dresden, Germany, 1307
Universitaet Erlangen-Nuerberg Klinik fur Neurologie
Erlangen, Germany, 91054
University Hospital of Essen
Essen, Germany, 45122
Universitatsklinik Frankfurt, Klinik und Poliklinik f. Neurochirurgie
Frankfurt, Germany, 60528
Neuroradiologie der Universitatsklinik Freiburg
Freiburg, Germany, D-79106
Universitatsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Neurochirurggische Universitatsklinik des Heidelberg
Heidelberg, Germany, 69120
Klinik und Poliklinik fur Neurochirurgie
Leipzip, Germany, 04103
Thechnical University - Klinikum rechts der Isar
Munich, Germany, 81675
University Regensburg
Regensburg, Germany, 93053
Hong Kong
Queen Mary Hospital
Hong Kong Island, Hong Kong
Prince od Wales Hospital
Shatin, Hong Kong
Hungary
Borsod-Abauj-Zemplen County Hospital and University Teaching Hospital
Borsod Abaui-Zemplen, Hungary
University of Pecs, Faculty of Medicine Neurosurgery Clinic
Pecs, Hungary, 7623
University of Szeged, Faculty of Medicine
Pecs, Hungary
India
Post Graduate Institute of Medical Education and Research
Chandigarh, India, 160012
CARE Hospital
Hyderbad, India, 5-4-199
King Edward Memorial Hospital
Rasta Path, India
Israel
Rambam Medical Centre
Haifa, Israel, 31096
Hadassah Universtity Medical Center
Jerusalem, Israel, 91120
Sheba Medical Centre
Tel Hashomer, Israel, 52621
Italy
Osepedale Maggiore Bellaria
Bologna, Italy, 40139
Azienda Ospedaliera di Careggi
Firenze, Italy, 50141
Azienda Osepedaliera San Giovanni - Addolorata
Rome, Italy, 184
Ospedale Maggiore
Verona, Italy, 37126
Mexico
Instituto Nacional de Neurologia y Neurocirugia
Mexico City, Mexico, 14269
Hospital Universitario "Dr. Jose Eleuterio Gonzalez" Universidad Autonoma de Nuevo Leon
Monterrey, Mexico, 64460
Netherlands
Elisabeth Ziekenhuis
Tilburg, Netherlands
Norway
Haukeland University Hospital, Helse Bergen HF
Bergen, Norway, 5021
Ulleval Univ Hosp
Oslo, Norway, 0407
Universitetssykehuset Nord-Norge
Tromso, Norway, N9038
Poland
Szpital Akademii Medycznej w Gdansku
Gdansk, Poland, 80-952
Samodzielny Publiczny Centralny Szpital Kliniczy w Warszawie
Warszawa, Poland, 02-097
Singapore
National Neuroscience Institute
Seng, Singapore, 308433
National University Hospital
Singapore, Singapore, 119074
Slovenia
University Clinical Centre Ljubljana
Ljubljana, Slovenia, 1525
General Hospital Maribor
Maribor, Slovenia, 2000
Spain
Hospital Vali d' Hebron
Barcelona, Spain, 08035
Hospital Universitari de Bellvitge
Barcelona, Spain, 08907
Complejo Hospotalario Virgen de las Nieves-Hospital de Rehabilitacion y Traumatologia
Granada, Spain, 18012
Hospital Universitario 12 se Octubre
Madrid, Spain, 28041
Hospital de Son Dureta
Palma de Mallorca, Spain, 07014
Sweden
Sahlgrenska University Hospital
Goteborg, Sweden, 41345
Linkoping University Hospital
Linkoping, Sweden, 58185
Lund University Hospital
Lund, Sweden, 22185
Switzerland
Kantonsspital Aarau
Aarau, Switzerland, 5001
Universitatsklinik Bern
Bern, Switzerland, 3010
Geneva University Hospital
Geneva, Switzerland, 1211
Universitatsspital Zurich
Zurich, Switzerland, 8091
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Taipei Veterans General Hospital
Taipei, Taiwan, 112
Sponsors and Collaborators
Actelion
Investigators
Study Director: Sebastien Roux, MD Actelion
  More Information

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
First Submitted: July 13, 2009
First Posted: July 15, 2009
Last Update Posted: May 15, 2015
Last Verified: April 2015

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

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