AzTrials
AzTrials

Aneurysmal Subarachnoid HemorrhagePhase 2CONSCIOUS-1NCT00111085

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

A Phase 2 study testing Clazosentan 1 mg/h, Clazosentan 5 mg/h and Clazosentan 15 mg/h in people with Aneurysmal Subarachnoid Hemorrhage, run by Idorsia Pharmaceuticals Ltd. at 16 sites in 2 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 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Aneurysmal Subarachnoid Hemorrhage
What is being tested?
Clazosentan 1 mg/h, Clazosentan 5 mg/h and Clazosentan 15 mg/h
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
413 participants
Where
16 sitesin 2 countries
Study dates
10 Jan 2005to 30 Mar 2006
Phase
Phase 2
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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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.
  • 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
  • Start of screening within 48 hours post onset of aSAH clinical symptoms
  • World Federation of Neurological Surgeons (WFNS) Grades I-IV, and those Grade V patients who improve to Grade IV or less after ventriculostomy
  • In the case of multiple aneurysms, the aneurysm that has ruptured is identified with a high likelihood during the screening period
Show all 9Show fewer
  • Women of childbearing potential with pre-treatment negative serum pregnancy test
  • 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
  • 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

Who cannot join

  • Patients with SAH due to other causes (e.g., trauma or rupture of fusiform or mycotic aneurysms)
  • Patients with intraventricular or intracerebral blood, in the absence of subarachnoid blood
  • No visualized clot or presence of only localized thin clot on CT (< 20 mm x 4 mm)
  • Presence of any degree of cerebral vasospasm on screening angiogram
  • Patients with hypotension (systolic blood pressure (SBP) <=90 mmHg) refractory to fluid therapy
  • Patients with neurogenic pulmonary edema or severe cardiac failure requiring inotropic support
Show all 13Show fewer
  • 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
  • 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)
  • 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
  • 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
  • Patients who have received thrombolytics, including intracisternal administration, intrathecal treatments and therapeutic hypothermia for treatment of the SAH
  • Patients who have received an investigational product within 28 days prior to randomization
  • Patients with current alcohol or drug abuse or dependence

Trial locations and contacts

16 sites in 2 countries.

16 sites in 2 countries

United States10 sites

  • Dr. Aldrich

    Baltimore, Maryland

  • Dr. Ogilvy

    Boston, Massachusetts

  • Dr. Zuccarello

    Cincinnati, Ohio

  • Dr. Woo

    Cleveland, Ohio

  • Dr. George A. Lopez

    Houston, Texas

  • Dr. Horner

    Indianapolis, Indiana

  • Dr. Giuseppe Lanzino

    Peoria, Illinois

  • Dr. Rosenwasser

    Philadelphia, Pennsylvania

  • Dr. Zager

    Philadelphia, Pennsylvania

  • Dr. Bullock

    Richmond, Virginia

Other trials in United States

Canada6 sites

  • Dr. Wong

    Calgary, Alberta

  • Dr. Findlay

    Edmonton, Alberta

  • Dr. Fleetwood

    Halifax, Nova Scotia

  • Dr. Bojanowski

    Montreal, Quebec

  • Dr. Ferguson

    Toronto, Ontario

  • Dr. Redekop

    Vancouver, British Columbia

Other trials in Canada

About this study

Official title: 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.

Being tested
Clazosentan 1 mg/h, Clazosentan 5 mg/h, Clazosentan 15 mg/h, Placebo
Keywords
delayed ischemic neurological deficits (DIND), vasospasm, clazosentan, cerebral vasospasm, computer tomography scan (CT scan), digital subtraction angiography (DSA), endothelin A receptor, aneurysmal subarachnoid hemorrhage (aSAH)
Medical subject headings
Subarachnoid Hemorrhage, Vasospasm, Intracranial

What participants receive

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

  • Clazosentan 1 mg/hDrug

    Also called ACT-108475

    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/hDrug

    Also called ACT-108475

    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/hDrug

    Also called ACT-108475

    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

  • PlaceboDrug

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

Study groups in NCT00111085
Study groupRoleWhat they receive
Clazosentan 1 mg/hExperimentalintravenous clazosentan at 1 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Receives: Drug: Clazosentan 1 mg/h
Clazosentan 5 mg/hExperimentalintravenous clazosentan at 5 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Receives: Drug: Clazosentan 5 mg/h
Clazosentan 15 mg/hExperimentalintravenous clazosentan at of 15 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Receives: Drug: Clazosentan 15 mg/h
PlaceboPlacebo comparatorintravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture
Receives: Drug: Placebo

What is being measured

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

  1. Occurrence of moderate or severe cerebral vasospasm, as measured by cerebral angiography

    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.

    Measured: Up to day 14

Secondary outcomes (6)

  1. 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

    Measured: Within 6 weeks

  2. 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

    Measured: Within 6 weeks

  3. 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

    Measured: Within 14 days

  4. 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

    Measured: Within 14 days

  5. Clinical outcome at 12 weeks post-aneurysm rupture as measured by the Modified Rankin Scale (mRS) score

    Measured: At 12 weeks

  6. Clinical outcome at 12 weeks post-aneurysm rupture as measured bythe Glasgow Outcome Scale - Extended Version (GOSE) score

    Measured: At 12 weeks

Timeline

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

  1. First posted18 May 2005 (estimated)
  2. Study start10 Jan 2005
  3. Primary completion30 Mar 2006
  4. Study completion30 Mar 2006

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 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Enrolment
413 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00111085
Sponsor's protocol ID
AC-054-201
Acronym
CONSCIOUS-1
Status last verified
Jul 2018
First submitted
17 May 2005
Last updated
10 Jul 2018
Results posted
No

Publications

  • 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.

    PubMed 31299650

  • 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.

    PubMed 29946013

  • 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.

    PubMed 27827324

  • 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.

    PubMed 27000643

  • 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.

    PubMed 26428322

  • 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.

    PubMed 26248048

  • 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.

    PubMed 25280913

  • 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.

    PubMed 24425125

  • 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.

    PubMed 23581590

  • 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.

    PubMed 22678087

  • 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.

    PubMed 21998061

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Clazosentan 1 mg/h, Clazosentan 5 mg/h and Clazosentan 15 mg/h in people with Aneurysmal Subarachnoid Hemorrhage, run by Idorsia Pharmaceuticals Ltd. at 16 sites in 2 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 9 inclusion and 13 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 10 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Occurrence of moderate or severe cerebral vasospasm, as measured by cerebral angiography (time frame: Up to day 14). 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 NCT00111085, which also lists 11 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 10 Jul 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in