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Aneurysmal Subarachnoid HemorrhagePhase 3CONSCIOUS-2NCT00558311

Clazosentan in Reducing Vasospasm-related Morbidity and All-cause Mortality in Adult Patients With Aneurysmal Subarachnoid Hemorrhage Treated by Surgical Clipping

A Phase 3 study testing Clazosentan in people with Aneurysmal Subarachnoid Hemorrhage, run by Idorsia Pharmaceuticals Ltd. at 117 sites in 29 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The aim of this study is to demonstrate that clazosentan, administered as a continuous intravenous infusion at 5 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 surgical… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Aneurysmal Subarachnoid Hemorrhage
What is being tested?
Clazosentan
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,157 participants
Where
117 sitesin 29 countries
Study dates
14 Dec 2007to 13 Jul 2010
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females aged 18 to 75 years (inclusive).
  • Patients with a ruptured saccular aneurysm, confirmed by angiography (digital subtraction angiography [DSA] or computed tomography angiography [CTA]), and which has been successfully secured by surgical clipping. The time of aneurysm rupture must be known or possible to estimate with a reasonable degree of certainty.
  • World Federation of Neurological Surgeons (WFNS) grade I-IV measured prior to the clipping procedure, and which does not worsen to grade V post-procedure (based on regular Glasgow Coma Scale [GCS])*
  • Patients with any diffuse clot (long axis > or = 20 mm, or any clot present across both hemispheres) on baseline CT scan.
  • 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.
  • 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.
  • Patients must be evaluable for WFNS grade prior to the clipping 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 12 hours post-procedure, but prior to randomization, ruling out any large procedure-related infarct.

Who cannot join

  • Patients with subarachnoid hemorrhage (SAH) due to causes other than a saccular aneurysm (e.g., trauma or rupture of fusiform or mycotic aneurysms).
  • Patients with intraventricular or intracerebral blood, in the absence of subarachnoid blood, or with only a local clot.
  • Presence of cerebral vasospasm seen on angiography prior to the clipping procedure.
  • Patients who experienced a major complication during the clipping procedure, such as massive bleeding, 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 clipping).*
  • Patients for whom study drug cannot be started within 56 hours after the aneurysm rupture.
  • Patients who have had their aneurysm secured by coiling only.
Show all 22Show fewer
  • Patients for whom it is known, at the time of screening, that certain follow-up, protocol-mandated imaging assessments will not be feasible.
  • Patients with hypotension (systolic blood pressure (SBP)< or = 90 mmHg) that is refractory to treatment.
  • Patients with aspiration pneumonia.
  • Patients with pulmonary edema or severe cardiac failure requiring inotropic support.
  • 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.
  • Significant kidney and/or liver disease, as defined by plasma creatinine > or = 2.5 mg/dL (221 micromol/l) and/or total bilirubin > 3 mg/dL (51.3 micromol/l) measured at the local site laboratory.
  • Patients receiving i.v. nimodipine, i.v. nicardipine, or fasudil hydrochloride, must have these drugs discontinued at least 4 hours prior to initiation of the study treatment.
  • Patients receiving statins for less than 2 weeks prior to admission must have them discontinued prior to study drug initiation.
  • Patients receiving 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.
  • Patients who have received an investigational product within 28 days prior to randomization or those who have already participated in the current study.
  • Patients unlikely to comply with the protocol (e.g., unable to return for follow-up visits).
  • Known hypersensitivity to other endothelin receptor antagonists.
  • Patients with current alcohol or drug abuse or dependence.
  • Further detail on exclusion criterion number 4:
  • "Large territorial infarct" refers to those infarcts detected during the clipping 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 the reversal of sedation (or waiting for the patient to recover from sedation) and the performance of a GCS examination (verbal scores in intubated patients may be extrapolated from the eye-opening and motor scores using the values provided in the table included in Section 3.9.1.2.1 of the protocol). In the event of a new major neurological deficit that does not improve within 12 hours after the clipping procedure, the patient cannot be included in the study.

Trial locations and contacts

117 sites in 29 countries.

117 sites in 29 countries

Germany12 sites

  • Charite Universitatsmedizin Berlin-Neurochirurgische Klinik-CVK

    Berlin, D-13353

  • University of Bonn Medical Center

    Bonn, 53105

  • Klinik und Poliklinik fur Neurochirurgie

    Dresden, 01307

  • University of Erlangen-Nurnberg

    Erlangen, 91054

  • University of Hospital of Essen

    Essen, 45147

  • Universitatsklinik Frankfurt, Klinik und Poliklinik fur Neurochirurgie

    Frankfurt, 60528

  • University Hospital of Hamburg

    Hamburg, 20246

  • Neurochirurggische Universitatsklinik des Heidelberg

    Heidelberg, 69120

  • Klinik und Poliklinik fur Neurochirurgie

    Leipzig, 04103

  • University Munich Groshadern

    Munich, 81377

  • Thechnical University-Klinikum rechts der Isar

    Munich, 81675

  • University Regensburg

    Regensburg, 93053

Other trials in Germany

United States11 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Virginia Health System-Department of Neurosurgery

    Charlottesville, Virginia, 22908

  • University of Cincinnati-Department of Neurosurgery

    Cincinnati, Ohio, 45219

  • University Hospitals Case Medical Center-Department of Neurosurgery

    Cleveland, Ohio, 44106

  • Colorado Neurological Institute

    Englewood, Colorado, 80113-2769

  • Columbia University Medical Center

    New York, New York, 10032

  • Thomas Jefferson University School of Medicine-Jefferson Hospital for Neuroscience

    Philadelphia, Pennsylvania, 19107

  • Barrow Neurosurgical Associates

    Phoenix, Arizona, 85013

  • Oregon Health & Science University-Oregon Stroke Center

    Portland, Oregon, 97239

  • Virginia Commonwealth University-Department of Neurosurgery

    Richmond, Virginia, 23284

  • State University of New York at Stony Brook-Health Sciences Center

    Stony Brook, New York, 11794-8122

Other trials in United States

Italy8 sites

  • Ospedale Bellaria-Maggiore Hospital

    Bologna, 40139

  • Ospedale Maurizio Bufalini

    Cesena, 47023

  • Azienda Ospedaliero-Universitaria di Careggi

    Florence, 50141

  • Ospedale Niguarda

    Milan, 20162

  • Nuovo Ospedale Sant' Agostino Estense

    Modena, 41100

  • Ospedale Civile di Padova

    Padova, 35128

  • Azienda Ospedaliero-Universitaria di

    Parma, 43100

  • Ospedale Civile Borgo Trento

    Verona, 37126

Other trials in Italy

Poland8 sites

  • Klinika Neurochirurgii AMB-Neurosurgery Clinic of Medical Academy

    Bialystok

  • Kathedra I Klinika Neurochirurghii I Neurotraumatologii Collegium Medicum im. L. Rydygiera w Bydgoszc

    Bydgoszcz, 85-094

  • Katedra Klinika Neurochirurgii Akademii Medycznej w Gdansku

    Gdansk, 80211

  • Samodzielny Publiczny Szpital Kliniczny Slaskiej Akademii Medycznej w Katowicach

    Katowice, 40-752

  • Oddzial Kliniczny Kliniki Neurochirurgii i Neurotrumatologii Szpitala, Uniwersyteckiego w Krakowie

    Krakow, 31-503

  • Katedra Neurochirurgii, Uniwersytet

    Lodz, 90-153

  • Katedra I Klinika Neurochirurgii i Dzieciecej

    Lublin, 20-090

  • Katedra IKlinika Neurochirurgii Akademii Medycznej w Warszawie Clinic

    Warsaw, 02-097

Other trials in Poland

Canada7 sites

  • University of Calgary Foothills Medical Center

    Calgary, T2N2T9AB

  • University of Alberta Hospital

    Edmonton, Alberta, T6G2B7

  • QEII Health Science Center

    Halifax, B3H3A7

  • CHUM Notre Dame

    Montreal, Quebec, H2L4M1

  • St Michael's Hospital, University

    Toronto, Ontario, M5C367

  • Toronto Western Hospital, University of Toronto

    Toronto, M5T2S8

  • Vancouver Hospital

    Vancouver, British Columbia, V5Z 1 M9BC

Other trials in Canada

Austria6 sites

  • Landeskrankenhaus

    Feldkirch, 6807

  • Landeskrankenhaus und Medizinische Universitat Graz

    Graz, 8036

  • Medizinsche Universitat

    Innsbruck, 6020

  • University Fur Neurochirurgie, SALK, Christian Doppler Hospital

    Salzburg, 5020

  • AKH University of Vienna, Medical University

    Vienna, 1090

  • Sozialmedizinisches Zentrum Ost (ZMZ-Ost) Donauspital Vienna

    Vienna, 1220

Other trials in Austria

China6 sites

  • Beijing Tian Tan Hospital

    Beijing, 100050

  • XuanWu Hospital Institute of Brain Vascular Disease

    Beijing, 100053 PR

  • Guangdong Province Chinese Medicine Hospital

    Guangzhou, 51000

  • 1st Affilated Hospital of Zhongshan

    Guangzhou, 510080

  • Shanghai Hua Shan Hospital

    Shanghai, 200040

  • Wuhan Tongji Hospital

    Wuhan, 430030

Other trials in China

India6 sites

  • Post Graduate Institute of Medical Education and Research

    Chandigarh, 160012

  • Post Graduate Institute of Medical Education

    Chandigarh, 160012

  • Nizam's Institute of Medical Sciences

    Hyderabaad, 500482

  • All India Insititute of Medicla Sciences (AIIMS)

    New Delhi, 110011

  • Sahyadri Specialty Hospital

    Pune, 411 004

  • Sahyadri Hospital

    Pune, 411005

Other trials in India

Switzerland6 sites

  • Kantonsspital Aarau

    Aarau, 5001

  • Universitatsklinik Bern

    Bern, 3010

  • Universitätsklinik Bern Klinik für Neurochirurgie

    Bern, 3010

  • Geneva University Hospital

    Geneva, 1211

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

  • Universitatsspital Zurich

    Zurich, 8091

Other trials in Switzerland

France5 sites

  • Pole d'Anesthesie Reanimation, CHU D'Angers

    Angers, 49933

  • Hopital Pellegrin

    Bordeaux, 33076

  • Hopital Neurologique et Neuro-Chirurgical Pierre Wertheimer

    Bron, 69677

  • Chu Hopital Gabriel Montpied

    Clermont-Ferrand, 63003

  • Hopital de la Timone

    Marseille, 13385

Other trials in France

Czechia4 sites

  • Faculty Hospital/FN Brno Bohunice

    Brno, 62500

  • Nemocnice Ceske Budejovice

    České Budějovice, 37087

  • Na Homolce Hospital Prague

    Prague, 15030

  • UVN Prague

    Prague, 16902

Other trials in Czechia

Spain4 sites

  • Hospital Del Mar

    Barcelona, 08003

  • Vall d'Hebron Hospital

    Barcelona, 08035

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital de Son Dureta

    Palma de Mallorca, 07014

Other trials in Spain

Croatia3 sites

  • Clinical Hospital "Dubrava"

    Zagreb, 10000

  • Clinical Hospital Dubrava

    Zagreb, 1000

  • University Hospital Sestre Milosrdnice

    Zagreb, 1000

Other trials in Croatia

Denmark3 sites

  • Copenhagen University Hospital

    Copenhagen, 2100

  • Copenhagen Country Hospital

    Glostrup Municipality, 2600

  • Odense University Hospital

    Odense, 5000

Other trials in Denmark

Finland3 sites

  • Helsinki University Central Hospital

    Helsinki, Fin-00029HUS

  • Oulu University Hospital

    Oulu, 90029OYS

  • Tampere University Central Hospital

    Tampere, 33521

Other trials in Finland

Norway3 sites

  • Haukeland University Hospital Helse Bergen HF

    Bergen, 5021

  • Ulleval University Hospital

    Oslo, 0407

  • Universitetssykehuset Nord-Norge

    Tromsø, N9038

Other trials in Norway

Sweden3 sites

  • Sahlgrenska

    Gothenburg, 41345

  • Lund University Hospital

    Lund, 22185

  • Uppsala University Hospital-Uppsala Akademiska Sjukhus

    Uppsala, 75185

Other trials in Sweden

Turkey (Türkiye)3 sites

  • Ibn-i Sina Hastanesi Ankara & Ankara Universitesi Tip Fakultesi

    Ankara, 06100

  • Ege Universitesi Tip Fak Hestanesi

    Bornova, 35100

  • Istanbul Universitesi, Istanbul Tip

    Istanbul, 34390

Other trials in Turkey (Türkiye)

Australia2 sites

  • Royal Brisbane Hospital

    Herston, 4029

  • The Alfred Hospital

    Melbourne, VIC 3004

Other trials in Australia

Hong Kong2 sites

  • Prince of Wales Hospital

    Hong Kong, NT

  • Queen Mary Hospital

    Hong Kong

Other trials in Hong Kong

Serbia2 sites

  • Clinical Center Nis

    Niš, 18000

  • Clinical Center Novi Sad

    Novi Sad, 21000

Other trials in Serbia

South Korea2 sites

  • Kyungpook National University

    Daegu, 700-721

  • Daejeon Eulji University Hospital

    Daejeon, 302-799

Other trials in South Korea

Ukraine2 sites

  • Regional Clinical Hospital by Mechnikov

    Dnipropetrovsk, 49,005

  • A. P. Romodanov Institute of Neurosurgery

    Kiev, 04 050

Other trials in Ukraine

Belgium1 site

  • Cliniques Universitaires Saint-Luc, Universite Catholique de

    Brussels, 1200

Other trials in Belgium

Latvia1 site

  • Riga Eastern Clinical University Hospital

    Riga, LV-1038

Other trials in Latvia

New Zealand1 site

  • Auckland Hospital

    Grafton, Auckland

Other trials in New Zealand

Russia1 site

  • Scientific Research Institute of Neurosurgery by Burdenko

    Moscow, 125 047

Other trials in Russia

Singapore1 site

  • National Neuroscience

    Singapore, 308433

Other trials in Singapore

Slovenia1 site

  • General Hospital Maribor

    Maribor, 2000

Other trials in Slovenia

About this study

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 Surgical Clipping.

The aim of this study is to demonstrate that clazosentan, administered as a continuous intravenous infusion at 5 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 surgical clipping. 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. Neurological signs or symptoms (depending on state of consciousness), in the presence of confirmed cerebral vasospasm on angiography (DSA or CTA), leading to the administration of a valid rescue therapy.

An independent Critical Events Committee (CEC) will adjudicate whether or not patients meet the primary endpoint and its individual morbidity components.

Being tested
Clazosentan, Placebo
Keywords
Aneurysmal, Subarachnoid, Hemorrhage, vasospasm, clazosentan, PIVLAZ, surgical clipping
Medical subject headings
Subarachnoid Hemorrhage, Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ClazosentanDrug

    Intravenous clazosentan administered by continuous infusion at 5 mg/h

  • PlaceboDrug

    Placebo administered by continuous infusion matching clazosentan administration

Study groups in NCT00558311
Study groupRoleWhat they receive
ClazosentanExperimentalA continuous intravenous infusion of clazosentan was started within 56 hours post-aSAH and was scheduled to continue during the hospitalization until Day 14 post-aSAH, or at least until Day 10.
Receives: Drug: Clazosentan
PlaceboPlacebo comparatorA continuous intravenous infusion of placebo-matching clazosentan was started within 56 hours post-aSAH and was scheduled to continue during the hospitalization until Day 14 post-aSAH, or at least until Day 10.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cerebral vasospasm-related morbidity and mortality of all-causes as defined by the protocol

    Measured: Within 6 weeks post-aSAH

Secondary outcomes (1)

  1. Glasgow Outcome Scale Extended (GOSE) at Week 12 post-aSAH, dichotomized into good (score > 4) and poor (score ≤ 4) outcome.

    Measured: Week 12 post-aSAH

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2007 (estimated)
  2. Study start14 Dec 2007
  3. Primary completion15 Jun 2010
  4. Study completion13 Jul 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,157 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00558311
Sponsor's protocol ID
AC-054-301
Acronym
CONSCIOUS-2
Status last verified
Feb 2020
First submitted
13 Nov 2007
Last updated
17 Feb 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 31394993

  • Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Marr A, Roux S, Kassell N. Randomised trial of clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping (CONSCIOUS-2). Acta Neurochir Suppl. 2013;115:27-31. doi: 10.1007/978-3-7091-1192-5_7.

    PubMed 22890639

  • Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Marr A, Roux S, Kassell N. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol. 2011 Jul;10(7):618-25. doi: 10.1016/S1474-4422(11)70108-9. Epub 2011 Jun 2.

    PubMed 21640651

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Clazosentan in people with Aneurysmal Subarachnoid Hemorrhage, run by Idorsia Pharmaceuticals Ltd. at 117 sites in 29 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 117 sites in Germany, United States, Italy, Poland, Canada and 24 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cerebral vasospasm-related morbidity and mortality of all-causes as defined by the protocol (time frame: Within 6 weeks post-aSAH). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00558311, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2020.

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