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.Estudio prospectivo, multicéntrico, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos, para evaluar la eficacia y seguridad de clazosentan en la reducción de la morbilidad y de todas las causas de mortalidad relacionadas con el vasoespasmo, en adultos con hemorragia subaracnoidea aneurismática tratados con clipaje quirúrgico - CONSCIOUS 2

Phase 1

• Conditions: Indication: Aneurysmal subarachnoid hemorrhageHemorragia Subaracnoidea aneurismática.; MedDRA version: 9.1Level: LLTClassification code 10042318Term: Subarachnoid haemorrhage NOS

• Registration Number: EUCTR2007-002584-27-ES
• Lead Sponsor: Actelion Pharmaceuticals Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-11-06
• Study Completion: 2010-07-13
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 765

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 >= 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.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 >= 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) <= 90 mmHg) that is refractory to treatment.
9. Patients with aspiration pneumonia or pulmonary edema.
10. Patients with 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 >= 2.5 mg/dL (221 µmol/l) and/or total bilirubin > 3 mg/dL (51.3 µmol/l) measured at the local site laboratory.
13. Patients receiving i.v. nimodipine or i.v. nicardipine 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

Study & Design

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