Clinical trial NCT00940095 (phase 3, status: terminated)
Conditions: aneurysmal subarachnoid hemorrhage
ICD codes: I60.8, I60.9, I69.020, I69.021, I69.022, I69.090, I69.091
Drugs: clazosentan 5 m/h, clazosentan 15 mg/h, placebo
SMILES: COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C)C=N2)N=C(N=C1OCCO)C1=CC=NC(=C1)C1=NN=NN1, COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C)C=N2)N=C(N=C1OCCO)C1=CC=NC(=C1)C1=NN=NN1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    lack of efficacy data from the phase 3 clinical study (ac-054-301; conscious-2)
  
Eligibility criteria:

        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], investigator's
             assessment), and which has been successfully* secured by endovascular coiling. 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
             endovascular coiling procedure, and which does not worsen to grade V post-procedure
             (based on regular Glasgow Coma Scale [GCS])

          4. Patients with any thick clot (short axis > or = 4 mm) on baseline CT scan
             (investigator's assessment).

          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.

        Exclusion Criteria :

          1. Subarachnoid hemorrhage (SAH) due to causes other than saccular aneurysm.

          2. Giant aneurysms (height or width > or = 25 mm).

          3. Intraventricular or intracerebral blood, in absence of subarachnoid blood, or or with
             only a thin clot (short axis < 4 mm)

          4. Cerebral vasospasm on angiography (investigator's assessment) prior to endovascular
             coiling (intraprocedural cerebral vasospasm is not an exclusion criterion).

          5. A major complication during the endovascular coiling procedure, such as massive
             intracranial bleeding, intracranial thromboembolism, coil migration, aneurysm
             perforation or rupture, arterial dissection, 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 >
             or = 12 hours post-aneurysm coiling)*.

          6. Current ruptured aneurysm previously secured (successfully or not) by clipping.

          7. Coiling material used, which has not been approved by local health authorities.

          8. Use of liquid embolism aneurysmal treatment or flow diverting device.

          9. Several aneurysms among which the ruptured one cannot be identified with certainty and
             which are not all secured during the coiling procedure.

         10. No end-of-procedure DSA.

         11. Another securing procedure planned for any aneurysm between randomization and Week 12
             post-aSAH.

         12. Study drug start >56 hours after the aneurysm rupture.

         13. Known, at time of screening, that certain follow-up, or protocol-mandated imaging
             assessments will not be feasible.

         14. Hypotension (systolic blood pressure < or = 90 mmHg) refractory to treatment.

         15. Aspiration pneumonia.

         16. Pulmonary edema or severe cardiac failure requiring inotropic support at time of
             randomization.

         17. Any severe or unstable concomitant condition or disease (e.g., known significant
             neurological deficit, cancer, hematological, coronary disease, psychiatric disorder),
             which would affect assessment of the safety or efficacy of the study drug
             (investigator's opinion).

         18. Significant kidney disease defined by plasma creatinine > or = 2.5 mg/dL (221
             micromol/l) and/or liver disease defined by total bilirubin > 2-fold Upper Limit of
             Normal as measured at local laboratory, and/or known diagnosis or clinical suspicion
             of liver cirrhosis.

         19. Infusion of i.v. nimodipine or i.v. nicardipine must have these drugs discontinued at
             least 4 hours prior to initiation of study treatment.

         20. Infusion of i.v. fasudil within 24-hour period preceding planned start of study drug
             initiation.

         21. Start of statins less than 2 weeks prior to admission must have them discontinued
             prior to study drug initiation.

         22. Infusion of 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.

         23. Intake of an investigational product including investigational coil material within 28
             days prior to randomization or those who have already participated in current study or
             CONSCIOUS-2 (AC-054-301).

         24. Unlikely event to comply with protocol (e.g., unable to return for follow-up visits).

         25. Known hypersensitivity to other endothelin receptor antagonists.26.current alcohol or
             drug abuse/dependence.

               -  "Large territorial infarct" refers to infarcts detected during the endovascular
                  coiling 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 reversal of sedation and performance of a GCS examination
                  (verbal scores in intubated patients may be extrapolated from the eye-opening and
                  motor scores using predefined values). If a new major neurological deficit does
                  not improve within 12 hours after the coiling procedure, the patient cannot be
                  included.