Clazosentan in Preventing the Occurrence of Cerebral Vasospasm Following an Aneurysmal Subarachnoid Hemorrhage (aSAH) (CONSCIOUS-1)

July 6, 2018 updated by: Idorsia Pharmaceuticals Ltd.

A Phase IIb, Multi-center, International, Double-blind, Randomized, Placebo-controlled, Parallel-group, Dose-finding Study for the Prevention of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage (aSAH) by Intravenous Administration of Clazosentan, a Selective Endothelin A (ETA) Receptor Antagonist

The purpose of the study is to measure how effective and safe three different doses of the drug clazosentan are in preventing vasospasm after subarachnoid hemorrhage.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

413

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Halifax, Nova Scotia, Canada
        • Dr. Fleetwood
    • Alberta
      • Calgary, Alberta, Canada
        • Dr. Wong
      • Edmonton, Alberta, Canada
        • Dr. Findlay
    • British Columbia
      • Vancouver, British Columbia, Canada
        • Dr. Redekop
    • Ontario
      • Toronto, Ontario, Canada
        • Dr. Ferguson
    • Quebec
      • Montreal, Quebec, Canada
        • Dr. Bojanowski
  • United States
    • Illinois
      • Peoria, Illinois, United States
        • Dr. Giuseppe Lanzino
    • Indiana
      • Indianapolis, Indiana, United States
        • Dr. Horner
    • Maryland
      • Baltimore, Maryland, United States
        • Dr. Aldrich
    • Massachusetts
      • Boston, Massachusetts, United States
        • Dr. Ogilvy
    • Ohio
      • Cincinnati, Ohio, United States
        • Dr. Zuccarello
      • Cleveland, Ohio, United States
        • Dr. Woo
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Dr. Rosenwasser
      • Philadelphia, Pennsylvania, United States
        • Dr. Zager
    • Texas
      • Houston, Texas, United States
        • Dr. George A. Lopez
    • Virginia
      • Richmond, Virginia, United States
        • Dr. Bullock

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. Male or female patients aged 18 to 70 years (inclusive) or male patients aged 45 to 70 (inclusive) or males aged 18 to 44 (inclusive) who are surgically or naturally sterile or can personally sign the core Informed Consent
  2. Patients with a ruptured saccular aneurysm that has been confirmed by digital subtraction angiography (DSA) and for which clipping or coiling (endovascular obliteration) is possible.
  3. Patients with a diffuse or localized thick subarachnoid clot on baseline CT scan. Measurements defining clot thickness and extension are as follows: Diffuse: Clot with long axis >= 20 mm, or any clot if present in both hemispheres Localized: Clot with long axis < 20 mm Thick: Clot with short axis >= 4 mm Thin: Clot with short axis < 4 mm
  4. Start of screening within 48 hours post onset of aSAH clinical symptoms
  5. World Federation of Neurological Surgeons (WFNS) Grades I-IV, and those Grade V patients who improve to Grade IV or less after ventriculostomy
  6. In the case of multiple aneurysms, the aneurysm that has ruptured is identified with a high likelihood during the screening period
  7. Women of childbearing potential with pre-treatment negative serum pregnancy test
  8. Patient is able to start the study drug infusion within 56 hours after the rupture of the aneurysm, and the procedure option (clipping or coiling) must either be started within a maximum of 12 hours after the start of study drug infusion or should have been already performed
  9. Written informed consent to participate in the study must be obtained from the patient or a legal representative prior to initiation of any study-related procedure and enrollment

Exclusion criteria:

  1. Patients with SAH due to other causes (e.g., trauma or rupture of fusiform or mycotic aneurysms)
  2. Patients with intraventricular or intracerebral blood, in the absence of subarachnoid blood
  3. No visualized clot or presence of only localized thin clot on CT (< 20 mm x 4 mm)
  4. Presence of any degree of cerebral vasospasm on screening angiogram
  5. Patients with hypotension (systolic blood pressure (SBP) <=90 mmHg) refractory to fluid therapy
  6. Patients with neurogenic pulmonary edema or severe cardiac failure requiring inotropic support
  7. 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
  8. Advanced kidney and/or liver disease, as defined by plasma creatinine >=2 mg/dl (177 micromol/l) and/or total bilirubin > 3 mg/dl (51.3 micromol/l)
  9. Any known or CT evidence of previous major cerebral damage (e.g., stroke [> 2 cm], traumatic brain injury [> 2 cm], previously treated cerebral aneurysm, arterial venous malformation [AVM]), or other preexisting cerebrovascular disorders, which may affect accurate diagnosis and evaluation of SAH
  10. Patients receiving prophylactic i.v. nimodipine or i.v. nicardipine. If present, these must be stopped at least 4 hours prior to initiation of the study treatment
  11. Patients who have received thrombolytics, including intracisternal administration, intrathecal treatments and therapeutic hypothermia for treatment of the SAH
  12. Patients who have received an investigational product within 28 days prior to randomization
  13. Patients with current alcohol or drug abuse or dependence

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clazosentan 1 mg/h
intravenous clazosentan at 1 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Drug: Clazosentan 1 mg/h
Subjects receive intravenous clazosentan at a rate of 1 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Other Names:
  • ACT-108475
Experimental: Clazosentan 5 mg/h
intravenous clazosentan at 5 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Drug: Clazosentan 5 mg/h
Subjects receive intravenous clazosentan at a rate of 5 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Other Names:
  • ACT-108475
Experimental: Clazosentan 15 mg/h
intravenous clazosentan at of 15 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Drug: Clazosentan 15 mg/h
Subjects receive intravenous clazosentan at a rate of 15 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Other Names:
  • ACT-108475
Placebo Comparator: Placebo
intravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Drug: Placebo
Subjects receive intravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of moderate or severe cerebral vasospasm, as measured by cerebral angiography
Time Frame: Up to day 14
If the patient develops clinical or sonographic changes suggestive of vasospasm prior to or after Day 9 ± 2 and until Day 14 post-aneurysm rupture, an angiogram will be performed to confirm the vasospasm. If vasospasm is documented prior to Day 9 ± 2, the Day 9 ± 2 angiogram is no longer required. In the case that a patient only develops clinical symptoms suggestive of vasospasm later than Day 9 ± 2 and up to Day 14, an additional angiogram should be performed to confirm the diagnosis of vasospasm. If the latter shows a higher grade of vasospasm than the previous one, it will be used for comparison to the baseline angiogram for evaluation of the primary endpoint.
Up to day 14

Secondary Outcome Measures

Outcome Measure
Time Frame
Occurrence of vasospasm-related morbidity, and mortality of all causes defined as the occurrence of death of any cause within the first 6 weeks post-aneurysm rupture OR
Time Frame: Within 6 weeks
Within 6 weeks
Occurrence of vasospasm-related morbidity, and mortality of all causes defined as the occurence of new cerebral infarct within first 6 weeks post-aneurysm rupture based on local investigator reading of post-baseline CT scans OR
Time Frame: Within 6 weeks
Within 6 weeks
Occurrence of vasospasm-related morbidity, and mortality of all causes defined as the occurence of delayed ischemic neurological deficits (DIND) due to vasospasm (based on investigator assessments) within 14 days post-aneurysm rupture OR
Time Frame: Within 14 days
Within 14 days
Occurrence of vasospasm-related morbidity, and mortality of all causes defined as occurrence of use of rescue medication due to vasospasm within 14 days post-aneurysm rupture
Time Frame: Within 14 days
Within 14 days
Clinical outcome at 12 weeks post-aneurysm rupture as measured by the Modified Rankin Scale (mRS) score
Time Frame: At 12 weeks
At 12 weeks
Clinical outcome at 12 weeks post-aneurysm rupture as measured bythe Glasgow Outcome Scale - Extended Version (GOSE) score
Time Frame: At 12 weeks
At 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Idorsia Pharmaceuticals Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 10, 2005

Primary Completion (Actual)

March 30, 2006

Study Completion (Actual)

March 30, 2006

Study Registration Dates

First Submitted

May 17, 2005

First Submitted That Met QC Criteria

May 17, 2005

First Posted (Estimate)

May 18, 2005

Study Record Updates

Last Update Posted (Actual)

July 10, 2018

Last Update Submitted That Met QC Criteria

July 6, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-054-201

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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