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

NCT ID: NCT00111085

Last Updated: 2018-07-10

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

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

413 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-10

Study Completion Date

2006-03-30

Brief Summary

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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.

Detailed Description

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Conditions

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Aneurysmal Subarachnoid Hemorrhage

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Study Groups

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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

Group Type EXPERIMENTAL

Clazosentan 1 mg/h

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Clazosentan 5 mg/h

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Clazosentan 15 mg/h

Intervention Type DRUG

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

Placebo

intravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Subjects receive intravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture

Interventions

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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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Placebo

Subjects receive intravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture

Intervention Type DRUG

Other Intervention Names

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ACT-108475 ACT-108475 ACT-108475

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Dr. Giuseppe Lanzino

Peoria, Illinois, United States

Site Status

Dr. Horner

Indianapolis, Indiana, United States

Site Status

Dr. Aldrich

Baltimore, Maryland, United States

Site Status

Dr. Ogilvy

Boston, Massachusetts, United States

Site Status

Dr. Zuccarello

Cincinnati, Ohio, United States

Site Status

Dr. Woo

Cleveland, Ohio, United States

Site Status

Dr. Rosenwasser

Philadelphia, Pennsylvania, United States

Site Status

Dr. Zager

Philadelphia, Pennsylvania, United States

Site Status

Dr. George A. Lopez

Houston, Texas, United States

Site Status

Dr. Bullock

Richmond, Virginia, United States

Site Status

Dr. Wong

Calgary, Alberta, Canada

Site Status

Dr. Findlay

Edmonton, Alberta, Canada

Site Status

Dr. Redekop

Vancouver, British Columbia, Canada

Site Status

Dr. Ferguson

Toronto, Ontario, Canada

Site Status

Dr. Bojanowski

Montreal, Quebec, Canada

Site Status

Dr. Fleetwood

Halifax, Nova Scotia, , Canada

Site Status

Countries

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United States Canada

References

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Eagles ME, Powell MF, Ayling OGS, Tso MK, Macdonald RL. Acute kidney injury after aneurysmal subarachnoid hemorrhage and its effect on patient outcome: an exploratory analysis. J Neurosurg. 2019 Jul 12;133(3):765-772. doi: 10.3171/2019.4.JNS19103. Print 2020 Sep 1.

Reference Type DERIVED
PMID: 31299650 (View on PubMed)

Ayling OGS, Ibrahim GM, Alotaibi NM, Gooderham PA, Macdonald RL. Anemia After Aneurysmal Subarachnoid Hemorrhage Is Associated With Poor Outcome and Death. Stroke. 2018 Aug;49(8):1859-1865. doi: 10.1161/STROKEAHA.117.020260.

Reference Type DERIVED
PMID: 29946013 (View on PubMed)

Ayling OG, Ibrahim GM, Alotaibi NM, Gooderham PA, Macdonald RL. Dissociation of Early and Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage. Stroke. 2016 Dec;47(12):2945-2951. doi: 10.1161/STROKEAHA.116.014794. Epub 2016 Nov 8.

Reference Type DERIVED
PMID: 27827324 (View on PubMed)

Nassiri F, Ibrahim GM, Badhiwala JH, Witiw CD, Mansouri A, Alotaibi NM, Macdonald RL. A Propensity Score-Matched Study of the Use of Non-steroidal Anti-inflammatory Agents Following Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2016 Dec;25(3):351-358. doi: 10.1007/s12028-016-0266-6.

Reference Type DERIVED
PMID: 27000643 (View on PubMed)

Tso MK, Ibrahim GM, Macdonald RL. Predictors of Shunt-Dependent Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage. World Neurosurg. 2016 Feb;86:226-32. doi: 10.1016/j.wneu.2015.09.056. Epub 2015 Sep 30.

Reference Type DERIVED
PMID: 26428322 (View on PubMed)

Young JM, Morgan BR, Misic B, Schweizer TA, Ibrahim GM, Macdonald RL. A Partial Least-Squares Analysis of Health-Related Quality-of-Life Outcomes After Aneurysmal Subarachnoid Hemorrhage. Neurosurgery. 2015 Dec;77(6):908-15; discussion 915. doi: 10.1227/NEU.0000000000000928.

Reference Type DERIVED
PMID: 26248048 (View on PubMed)

Ibrahim GM, Macdonald RL. The network topology of aneurysmal subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):895-901. doi: 10.1136/jnnp-2014-308992. Epub 2014 Oct 3.

Reference Type DERIVED
PMID: 25280913 (View on PubMed)

Ibrahim GM, Morgan BR, Macdonald RL. Patient phenotypes associated with outcomes after aneurysmal subarachnoid hemorrhage: a principal component analysis. Stroke. 2014 Mar;45(3):670-6. doi: 10.1161/STROKEAHA.113.003078. Epub 2014 Jan 14.

Reference Type DERIVED
PMID: 24425125 (View on PubMed)

Ibrahim GM, Fallah A, Macdonald RL. Clinical, laboratory, and radiographic predictors of the occurrence of seizures following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2013 Aug;119(2):347-52. doi: 10.3171/2013.3.JNS122097. Epub 2013 Apr 12.

Reference Type DERIVED
PMID: 23581590 (View on PubMed)

Ibrahim GM, Macdonald RL. Electrocardiographic changes predict angiographic vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2012 Aug;43(8):2102-7. doi: 10.1161/STROKEAHA.112.658153. Epub 2012 Jun 7.

Reference Type DERIVED
PMID: 22678087 (View on PubMed)

Ibrahim GM, Weidauer S, Vatter H, Raabe A, Macdonald RL. Attributing hypodensities on CT to angiographic vasospasm is not sensitive and unreliable. Stroke. 2012 Jan;43(1):109-12. doi: 10.1161/STROKEAHA.111.632745. Epub 2011 Oct 13.

Reference Type DERIVED
PMID: 21998061 (View on PubMed)

Other Identifiers

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AC-054-201

Identifier Type: -

Identifier Source: org_study_id

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