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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00558311




Registration number
NCT00558311
Ethics application status
Date submitted
13/11/2007
Date registered
14/11/2007

Titles & IDs
Public title
Clazosentan in Reducing Vasospasm-related Morbidity and All-cause Mortality in Adult Patients With Aneurysmal Subarachnoid Hemorrhage Treated by Surgical Clipping
Scientific 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.
Secondary ID [1] 0 0
AC-054-301
Universal Trial Number (UTN)
Trial acronym
CONSCIOUS-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aneurysmal Subarachnoid Hemorrhage 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Clazosentan
Treatment: Drugs - Placebo

Experimental: Clazosentan - A 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.

Placebo comparator: Placebo - A 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.


Treatment: Drugs: Clazosentan
Intravenous clazosentan administered by continuous infusion at 5 mg/h

Treatment: Drugs: Placebo
Placebo administered by continuous infusion matching clazosentan administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cerebral vasospasm-related morbidity and mortality of all-causes as defined by the protocol
Timepoint [1] 0 0
Within 6 weeks post-aSAH
Secondary outcome [1] 0 0
Glasgow Outcome Scale Extended (GOSE) at Week 12 post-aSAH, dichotomized into good (score > 4) and poor (score = 4) outcome.
Timepoint [1] 0 0
Week 12 post-aSAH

Eligibility
Key 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]), 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.
3. 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])*
4. Patients with any diffuse clot (long axis > or = 20 mm, or any clot present across both hemispheres) on baseline CT scan.
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.

* 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with subarachnoid hemorrhage (SAH) due to causes other than a saccular aneurysm (e.g., trauma or rupture of fusiform or mycotic aneurysms).
2. Patients with intraventricular or intracerebral blood, in the absence of subarachnoid blood, or with only a local clot.
3. Presence of cerebral vasospasm seen on angiography prior to the clipping procedure.
4. 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).*
5. Patients for whom study drug cannot be started within 56 hours after the aneurysm rupture.
6. Patients who have had their aneurysm secured by coiling only.
7. Patients for whom it is known, at the time of screening, that certain follow-up, protocol-mandated imaging assessments will not be feasible.
8. Patients with hypotension (systolic blood pressure (SBP)< or = 90 mmHg) that is refractory to treatment.
9. Patients with aspiration pneumonia.
10. Patients with pulmonary edema or severe cardiac failure requiring inotropic support.
11. 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.
12. 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.
13. 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.
14. Patients receiving statins for less than 2 weeks prior to admission must have them discontinued prior to study drug initiation.
15. 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.
16. Patients who have received an investigational product within 28 days prior to randomization or those who have already participated in the current study.
17. Patients unlikely to comply with the protocol (e.g., unable to return for follow-up visits).
18. Known hypersensitivity to other endothelin receptor antagonists.
19. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/12/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/07/2010
Sample size
Target
Accrual to date
Final
1157
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Brisbane Hospital - Herston
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
VIC 3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
Colorado
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United States of America
State/province [3] 0 0
Massachusetts
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United States of America
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New York
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United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Austria
State/province [9] 0 0
Feldkirch
Country [10] 0 0
Austria
State/province [10] 0 0
Graz
Country [11] 0 0
Austria
State/province [11] 0 0
Innsbruck
Country [12] 0 0
Austria
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Salzburg
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Austria
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Vienna
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Belgium
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Brussels
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Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
British Columbia
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
Canada
State/province [19] 0 0
Calgary
Country [20] 0 0
Canada
State/province [20] 0 0
Halifax
Country [21] 0 0
Canada
State/province [21] 0 0
Toronto
Country [22] 0 0
China
State/province [22] 0 0
Beijing
Country [23] 0 0
China
State/province [23] 0 0
Guangzhou
Country [24] 0 0
China
State/province [24] 0 0
Shanghai
Country [25] 0 0
China
State/province [25] 0 0
Wuhan
Country [26] 0 0
Croatia
State/province [26] 0 0
Zagreb
Country [27] 0 0
Czechia
State/province [27] 0 0
Brno
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Czechia
State/province [28] 0 0
Ceske Budejovice
Country [29] 0 0
Czechia
State/province [29] 0 0
Prague
Country [30] 0 0
Denmark
State/province [30] 0 0
Copenhagen
Country [31] 0 0
Denmark
State/province [31] 0 0
Glostrup
Country [32] 0 0
Denmark
State/province [32] 0 0
Odense
Country [33] 0 0
Finland
State/province [33] 0 0
Helsinki
Country [34] 0 0
Finland
State/province [34] 0 0
Oulu
Country [35] 0 0
Finland
State/province [35] 0 0
Tampere
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France
State/province [36] 0 0
Angers
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France
State/province [37] 0 0
Bordeaux
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France
State/province [38] 0 0
Bron
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France
State/province [39] 0 0
Clermont Ferrand
Country [40] 0 0
France
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Marseille
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Germany
State/province [41] 0 0
Berlin
Country [42] 0 0
Germany
State/province [42] 0 0
Bonn
Country [43] 0 0
Germany
State/province [43] 0 0
Dresden
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Germany
State/province [44] 0 0
Erlangen
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Germany
State/province [45] 0 0
Essen
Country [46] 0 0
Germany
State/province [46] 0 0
Frankfurt
Country [47] 0 0
Germany
State/province [47] 0 0
Hamburg
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Germany
State/province [48] 0 0
Heidelberg
Country [49] 0 0
Germany
State/province [49] 0 0
Leipzig
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Germany
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Munich
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Germany
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Regensburg
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Hong Kong
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Hong Kong
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India
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Chandigarh
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India
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Hyderabaad
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India
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New Delhi
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India
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Pune
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Italy
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Bologna
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Italy
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Cesena
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Italy
State/province [59] 0 0
Firenze
Country [60] 0 0
Italy
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Milan
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Italy
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Modena
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Italy
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Padova
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Italy
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Parma
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Italy
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Verona
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Korea, Republic of
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DaeGu
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Korea, Republic of
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Daejeon
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Latvia
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Riga
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New Zealand
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Grafton
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Norway
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Bergen
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Norway
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Oslo
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Norway
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Tromsö
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Poland
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Bialystok
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Bydgoszcz
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Gdansk
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Poland
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Katowice
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Poland
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Krakow
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Lodz
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Poland
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Lublin
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Poland
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Warszawa
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Russian Federation
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Moscow
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Serbia
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Nis
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Serbia
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Novi Sad
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Singapore
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Singapore
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Slovenia
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Maribor
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Spain
State/province [85] 0 0
Barcelona
Country [86] 0 0
Spain
State/province [86] 0 0
Madrid
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Spain
State/province [87] 0 0
Palma de Mallorca
Country [88] 0 0
Sweden
State/province [88] 0 0
Goteborg
Country [89] 0 0
Sweden
State/province [89] 0 0
Lund
Country [90] 0 0
Sweden
State/province [90] 0 0
Uppsala
Country [91] 0 0
Switzerland
State/province [91] 0 0
Aarau
Country [92] 0 0
Switzerland
State/province [92] 0 0
Bern
Country [93] 0 0
Switzerland
State/province [93] 0 0
Geneva
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Switzerland
State/province [94] 0 0
St Gallen
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Switzerland
State/province [95] 0 0
Zurich
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Turkey
State/province [96] 0 0
Ankara
Country [97] 0 0
Turkey
State/province [97] 0 0
Bornova
Country [98] 0 0
Turkey
State/province [98] 0 0
Istanbul
Country [99] 0 0
Ukraine
State/province [99] 0 0
Dnipropetrovsk
Country [100] 0 0
Ukraine
State/province [100] 0 0
Kiev

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Idorsia Pharmaceuticals Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Idorsia Pharmaceuticals Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT00558311