Clazosentan in Aneurysmal Subarachnoid Hemorrhage

NCT ID: NCT00940095

Last Updated: 2018-07-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

577 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-01

Study Completion Date

2011-01-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Aneurysmal Subarachnoid Hemorrhage

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Clazosentan 5 mg/h

Continuous intravenous infusion of clazosentan (5 mg/h) started within 56 hours post-aSAH and scheduled to continue until Day 14 post-aSAH, or at least until Day 10 post-aSAH, for patients discharged before Day 14

Group Type EXPERIMENTAL

Clazosentan 5 m/h

Intervention Type DRUG

Continuous intravenous infusion of clazosentan (5 mg/h)

Clazosentan 15 mg/h

Continuous intravenous infusion of clazosentan (15 mg/h) started within 56 hours post-aSAH and scheduled to continue until Day 14 post-aSAH, or at least until Day 10 post-aSAH, for patients discharged before Day 14

Group Type EXPERIMENTAL

Clazosentan 15 mg/h

Intervention Type DRUG

Continuous intravenous infusion of clazosentan clazosentan (15 mg/h)

Placebo

Continuous intravenous infusion of placebo matching clazosentan started within 56 hours post-aSAH and scheduled to continue until Day 14 post-aSAH, or at least until Day 10 post-aSAH, for patients discharged before Day 14

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Continuous intravenous infusion of placebo-matching clazosentan

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Clazosentan 5 m/h

Continuous intravenous infusion of clazosentan (5 mg/h)

Intervention Type DRUG

Clazosentan 15 mg/h

Continuous intravenous infusion of clazosentan clazosentan (15 mg/h)

Intervention Type DRUG

Placebo

Continuous intravenous infusion of placebo-matching clazosentan

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

ACT-108475 (AXV-034343) ACT-108475 (AXV-034343)

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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 \[GCS\])
4. Patients with any thick clot (short axis \> or = 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.

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 or with only a thin clot (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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Sebastien Roux, MD

Role: STUDY_DIRECTOR

Actelion

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Glendale Adventist Medical Center

Glendale, California, United States

Site Status

UCSF Medical Centre

San Francisco, California, United States

Site Status

Stanford Hospital and Clinis

Stanford, California, United States

Site Status

Colorado Neurological Institute

Englewood, Colorado, United States

Site Status

Yale Univerity School of Medicine

New Haven, Connecticut, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Illnois

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Boston Medical Centre

Boston, Massachusetts, United States

Site Status

William Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Barnes_Jewish Hospital

St Louis, Missouri, United States

Site Status

Capital Health System Inc. d/b/a The Stroke and Cerebrovascular Center of New Jersey

Trenton, New Jersey, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

New York Presbyteruan Hospital - Weill Cornell Medical Centre

New York, New York, United States

Site Status

State University of New York at Stony Brook

Stony Brook, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Thomas Jefferson University School of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Texas Southwestern Zale Lipshy Hospital

Dallas, Texas, United States

Site Status

Univ. of VA Health System

Charlottesville, Virginia, United States

Site Status

Virginia Commonwealth University Medical Centre

Richmond, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Hospital Aleman

Buenos Aires, , Argentina

Site Status

Clinica De Sol

Buenos Aires, , Argentina

Site Status

ENERI

Buenos Aires, , Argentina

Site Status

Gold Coast Hospital

Southport, Queensland, Australia

Site Status

Royal Brisbane & Women's Hosptal

Brisbane, , Australia

Site Status

Royal Prince Alfred Hosptial

Camperdown, , Australia

Site Status

Monash Medical Centre

Clayton, , Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, , Australia

Site Status

Landeskrankenhaus und Medizinische Universitat

Graz, , Austria

Site Status

Medizinsche Universitat Innsbruck

Innsbruck, , Austria

Site Status

University Fur Neurochirurgie, SALK, Christian Doppler Hospital

Salzburg, , Austria

Site Status

AKH University of Vienna, Medical Univ. Of Neurosurgery

Vienna, , Austria

Site Status

UZ Antwerpen

Antwerp, , Belgium

Site Status

ULB Erasme

Brussels, , Belgium

Site Status

UZ Brussels

Brussels, , Belgium

Site Status

UCL Saint-Luc

Brussels, , Belgium

Site Status

UZ Brussels

Brussels, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

UZ Gasthuisberg

Leuven, , Belgium

Site Status

Hospital das Clinicas da UFMG

Belo Horizonte, , Brazil

Site Status

Hospital de Clinicas da Universidade Federal do Parana

Curitiba, , Brazil

Site Status

Clinica de Neurologia de

Joinville, , Brazil

Site Status

Hospital de Clínicas de Niteroí

Niteroí, , Brazil

Site Status

Hospital Moinhos de Vento

Porto Alegre, , Brazil

Site Status

Hospital Santa Marcelina

São Paulo, , Brazil

Site Status

Santa Case de Misericordia de Sobral

Sobral, , Brazil

Site Status

University of Calgary - Foothills Medical Center

Calgary, Alberta, Canada

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Vancouver Hospital & Health Sciences

Vancouver, British Columbia, Canada

Site Status

QEII Heath Sciences Center - Halifax Infirmary

Halifax, Nova Scotia, Canada

Site Status

Hamilton General Hospital

Toronto, Ontario, Canada

Site Status

St. Michael's Hospital, University of Toronto

Toronto, Ontario, Canada

Site Status

CHUM Hospital - Notre Dame

Montreal, Quebec, Canada

Site Status

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Site Status

Hopital de I'Enfant-Jesus

Québec, , Canada

Site Status

Hospital Regional de Concepción

Concepción, , Chile

Site Status

Institute de Neurocirugia

Santiago, , Chile

Site Status

Hospital Clinico Pontificia Universidad Católica de Chile

Santiago, , Chile

Site Status

Clinica Davila

Santiago, , Chile

Site Status

Hospital Carlos Van Buren

Valparaíso, , Chile

Site Status

Fakultni nemocnice Bmo

Brno, , Czechia

Site Status

Nemocnice Ceske Budejovice

České Budějovice, , Czechia

Site Status

Fakultní nemocnice Ostrava

Ostrava, , Czechia

Site Status

Fakultni nemocnice Ostrava

Ostrava, , Czechia

Site Status

Nemocnice Na Homolce

Prague, , Czechia

Site Status

ÚVN Praha

Prague, , Czechia

Site Status

Fakultni nemocnice Homoice

Prague, , Czechia

Site Status

Masarykova nemocnice Usti n. Labem

Ústí nad Labem, , Czechia

Site Status

The Neuroscience Center, Copenhagen University Hospital

Copenhagen, , Denmark

Site Status

Glostrup Hospital

Glostrup Municipality, , Denmark

Site Status

Odense University Hospital

Odense, , Denmark

Site Status

Helsinki University Central Hospital

Helsinki, , Finland

Site Status

Tampere University Central Hospital (TAYS)

Tampere, , Finland

Site Status

CHU d'Angers

Angers, , France

Site Status

Hopital Pellegrin

Bordeaux, , France

Site Status

Hopital neurologique et Neuro-Chirurgical Pierre Wertheimer

Bron, , France

Site Status

Hopital Henru Mondor

Créteil, , France

Site Status

Hopital General

Dijon, , France

Site Status

Hopital de la Timone - CHU de Marseille

Marseille, , France

Site Status

Hopital Gui de Chauliac

Montpellier, , France

Site Status

Hopital central

Nancy, , France

Site Status

Universitatsklinikum Augsburg Clinic for Diagnostic Radiology and Neuroradiology

Augsburg, , Germany

Site Status

Charite Universitatsmedzin Berlin

Berlin, , Germany

Site Status

Universitatsklinikum Bonn

Bonn, , Germany

Site Status

University of Bonn Medical Center

Bonn, , Germany

Site Status

Klinik imd Poliklinik fur Neurochirurgie

Dresden, , Germany

Site Status

Universitaet Erlangen-Nuerberg Klinik fur Neurologie

Erlangen, , Germany

Site Status

University Hospital of Essen

Essen, , Germany

Site Status

Universitatsklinik Frankfurt, Klinik und Poliklinik f. Neurochirurgie

Frankfurt, , Germany

Site Status

Neuroradiologie der Universitatsklinik Freiburg

Freiburg im Breisgau, , Germany

Site Status

Universitatsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Neurochirurggische Universitatsklinik des Heidelberg

Heidelberg, , Germany

Site Status

Klinik und Poliklinik fur Neurochirurgie

Leipzig, , Germany

Site Status

Thechnical University - Klinikum rechts der Isar

Munich, , Germany

Site Status

University Regensburg

Regensburg, , Germany

Site Status

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Prince od Wales Hospital

Shatin, , Hong Kong

Site Status

Borsod-Abauj-Zemplen County Hospital and University Teaching Hospital

Miskolc, Borsod-Abauj Zemplen county, Hungary

Site Status

University of Pecs, Faculty of Medicine Neurosurgery Clinic

Pécs, , Hungary

Site Status

University of Szeged, Faculty of Medicine

Pécs, , Hungary

Site Status

Post Graduate Institute of Medical Education and Research

Chandigarh, , India

Site Status

CARE Hospital

Hyderabad, , India

Site Status

King Edward Memorial Hospital

Pune, , India

Site Status

Rambam Medical Centre

Haifa, , Israel

Site Status

Hadassah Universtity Medical Center

Jerusalem, , Israel

Site Status

Sheba Medical Centre

Tel Litwinsky, , Israel

Site Status

Osepedale Maggiore Bellaria

Bologna, , Italy

Site Status

Azienda Ospedaliera di Careggi

Florence, , Italy

Site Status

Azienda Osepedaliera San Giovanni - Addolorata

Rome, , Italy

Site Status

Ospedale Maggiore

Verona, , Italy

Site Status

Instituto Nacional de Neurologia y Neurocirugia

Mexico City, , Mexico

Site Status

Hospital Universitario "Dr. Jose Eleuterio Gonzalez" Universidad Autonoma de Nuevo Leon

Monterrey, , Mexico

Site Status

Elisabeth Ziekenhuis

Tilburg, , Netherlands

Site Status

Haukeland University Hospital, Helse Bergen HF

Bergen, , Norway

Site Status

Ulleval Univ Hosp

Oslo, , Norway

Site Status

Universitetssykehuset Nord-Norge

Tromsø, , Norway

Site Status

Szpital Akademii Medycznej w Gdansku

Gdansk, , Poland

Site Status

Samodzielny Publiczny Centralny Szpital Kliniczy w Warszawie

Warsaw, , Poland

Site Status

National University Hospital

Singapore, , Singapore

Site Status

National Neuroscience Institute

Singapore, , Singapore

Site Status

University Clinical Centre Ljubljana

Ljubljana, , Slovenia

Site Status

General Hospital Maribor

Maribor, , Slovenia

Site Status

Hospital Vali d' Hebron

Barcelona, , Spain

Site Status

Hospital Universitari de Bellvitge

Barcelona, , Spain

Site Status

Complejo Hospotalario Virgen de las Nieves-Hospital de Rehabilitacion y Traumatologia

Granada, , Spain

Site Status

Hospital Universitario 12 se Octubre

Madrid, , Spain

Site Status

Hospital de Son Dureta

Palma de Mallorca, , Spain

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Linkoping University Hospital

Linköping, , Sweden

Site Status

Lund University Hospital

Lund, , Sweden

Site Status

Kantonsspital Aarau

Aarau, , Switzerland

Site Status

Universitatsklinik Bern

Bern, , Switzerland

Site Status

Geneva University Hospital

Geneva, , Switzerland

Site Status

Universitatsspital Zurich

Zurich, , Switzerland

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Australia Austria Belgium Brazil Canada Chile Czechia Denmark Finland France Germany Hong Kong Hungary India Israel Italy Mexico Netherlands Norway Poland Singapore Slovenia Spain Sweden Switzerland Taiwan

References

Explore related publications, articles, or registry entries linked to this study.

Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Nowbakht P, Roux S, Kassell N. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke. 2012 Jun;43(6):1463-9. doi: 10.1161/STROKEAHA.111.648980. Epub 2012 Mar 8.

Reference Type RESULT
PMID: 22403047 (View on PubMed)

Mayer SA, Aldrich EF, Bruder N, Hmissi A, Macdonald RL, Viarasilpa T, Marr A, Roux S, Higashida RT. Thick and Diffuse Subarachnoid Blood as a Treatment Effect Modifier of Clazosentan After Subarachnoid Hemorrhage. Stroke. 2019 Oct;50(10):2738-2744. doi: 10.1161/STROKEAHA.119.025682. Epub 2019 Aug 9.

Reference Type DERIVED
PMID: 31394993 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

AC-054-302

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

The Intra-arterial Vasospasm Trial
NCT01996436 TERMINATED PHASE4