A study to evaluate the safety and potential therapeutic benefit of use of clazosentan in reversing cerebral vasospasm (a narrowing of blood vessels in the brain) in patients who have suffered a condition known as aneurysmal subarachnoid hemorrhage caused by bleeding onto the surface of the brain from a ruptured brain aneurysm

Phase 1

• Conditions: Aneurysmal subarachnoid hemorrhage (aSAH); cerebral vasospasm; MedDRA version: 19.1Level: LLTClassification code 10047164Term: Vasospasm cerebralSystem Organ Class: 100000004852; MedDRA version: 19.1Level: LLTClassification code 10042320Term: Subarachnoid hemorrhageSystem Organ Class: 100000004863; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-002721-18-FI
• Lead Sponsor: Actelion Pharmaceuticals Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-12-18
• Last Update Posted: 29 May 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

- Signed informed consent from the subject or proxy/legal representative
- Aged 18 to 65 years (inclusive)
- Aneurysmal subarachnoid hemorrhage (aSAH), confirmed by digital subtraction angiogram (DSA) or computed tomography angiogram (CTA), successfully secured by surgical clipping or endovascular coiling within 72 hours of rupture
- World Federation of Neurological Surgeons (WFNS) grade 1-4 at admission, and which must not increase to grade 5 at the time of enrollment
- Moderate or severe global cerebral vasospasm at the time of enrollment, documented by digital subtraction angiography (DSA) performed not earlier than 48 hours post aneurysm-securing procedure
- Women of childbearing potential must have a negative serum pregnancy test at screening and must use a reliable method of contraception from hospital discharge up to 30 days after discontinuation of study drug infusion, and fertile males must use a condom as a contraceptive method during this same period
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- SAH due to causes other than a saccular aneurysm
- Any moderate or severe cerebral vasospasm on angiography prior to the aneurysm-securing procedure.
- Presence of a new or worsened cerebral infarct or evidence of significant bleeding post aneurysm-securing procedure, or re-bleeding, on a CT scan performed within 24 hours prior to enrollment.
- Total bilirubin > 2 times the upper limit of normal, and / or a known diagnosis or clinical suspicion of liver cirrhosis or moderate to severe hepatic impairment.
- Any severe or unstable concomitant condition or disease (e.g., cancer, hematological, or coronary disease) or chronic condition (e.g., drug abuse, severe alcoholism), which, in the opinion of the investigator, would interfere with the assessment of the safety or effect of the study treatment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate whether clazosentan has an early effect in reversing angiographically-confirmed cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage treated by endovascular coiling or surgical clipping;Secondary Objective: - To evaluate the safety and tolerability of clazosentan<br>- To explore the effect of clazosentan on angiographic cerebral circulation time (CCT) and Transcranial Doppler (TCD) velocities;Primary end point(s): successful reversal* of global cerebral vasospasm 3 hours post-study drug initiation, derived from the central Independent Review Committee (IRC) assessment. <br>*Successful reversal is defined as an improvement in at least one level of severity on the global vasospasm assessment” (i.e., from severe to moderate, mild, or none, or from moderate to mild or none), evaluated on Digital subtraction angiogram (DSA);Timepoint(s) of evaluation of this end point: at baseline and at 3 hours post-study drug initiation

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1- Successful reversal of global cerebral vasospasm 24 hours (+/– 6 h) post-study drug initiation, derived from the central IRC assessment <br>2- Maximum change from baseline in angiographic cerebral circulation time derived from the central IRC assessment <br>3- Safety profile including incidence of adverse events;Timepoint(s) of evaluation of this end point: 1- at baseline and 24 hours post-study drug initiation <br>2-at baseline and at 3 hours and 24 hours post-study drug initiation <br>3- up to 30 days after study drug discontinuation