Subarachnoid hemorrhage MedDRA version: 20.1 Level: LLT Classification code 10042320 Term: Subarachnoid hemorrhage System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Cinryze, C1 inhibitor (human)
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: C1 inhibitor, human
Other descriptive name: C1 ESTERASE INHIBITOR (HUM
Sponsors
Haaglanden Medisch Centrum
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: - Confirmed diagnosis of aneurysmal subarachnoid hemorrhage on CT-scan or lumbar puncture (in the presence of a negative CT-scan); - Age = 18 years on admission; - WFNS grade 1-5 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 68
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: - Subarachnoid hemorrhage deemed most likely to ‘peri mesencephalic’ origin after consideration of history, clinical examination and radiological findings (including angiographic imaging); - Subarachnoid hemorrhage deemed most likely of post-traumatic origin after consideration of history, clinical examination and radiological findings (including angiographic imaging); - Participation in another clinical therapeutic study; - Patients with a known hereditary complement deficiency (including hereditary angioedema); - Patients with a history of sensibility to blood products or C1-inhibitor; - Patients with a history of thrombosis; - Pregnant woman
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: To determine the safety and efficacy of 6000 IU C1-INH in patients with subarachnoid hemorrhage (SAH) Primary hypothesis: The hypothesis is that random assignment to C1-INH in SAH will lead to a reduction in delayed cerebral ischemia (DCI) compared to random assignment to placebo. Furthermore, to access safety, no difference should be detected in complication rate during hospitalization between the two groups ;Secondary Objective: Secondary Objective: To determine differences between C1-INH and placebo treatment in the following outcomes for patients with SAH: -Clinical outcomes: cerebral infarction on brain CT/MRI, mortality, hospital and ICU length of stay, ventilator days, hospital disposition, functional outcome (mRS and GOSE), cognitive function (MoCA) and quality of life (EQ-5D-5L and SF-36) -Neurological damage: BANYAN (GFAP/UCHL-1) blood biomarker -Complement activation: human serum (WIESLAB assay), total terminal complement activity levels (CH50) and protein levels of complement component (C3b/C, C4b/C and C5b-9) in plasma and CSF -Coagulation cascade activation (PT, aPPT, PLT, D-dimer, fibrinogen) -Inflammatory markers in serum and CSF (TNF-alpha, intraleukin) -Level of C1-inhibitor activity in plasma and CSF ;Primary end point(s): Efficacy: To assess efficacy of C1-INH in SAH patients, the difference of delayed cerebral ischemia (DCI) will be analysed between the treatment groups. The criteria consisted of either a new focal neurological impairment (such as hemiparesis, aphasia, apraxia, hemianopia, or neglect), or a decrease of at least 2 points on the Glasgow Coma Scale (either on the total score or on one of its individual components). This should last for at least 1 hour, is not apparent immediately after aneurysm occlusion, and cannot be attributed to other causes by means of clinical assessment, CT or MRI scanning of the brain, and appropriate laboratory studies (e.g. hydrocephalus or rebleeding). Safety: As | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): During hospitalization: - Cerebral infarction on brain CT at 14 days - Mortality - Daily neurological condition measured by GCS during the first 14 days - Complement activity in serum and CSF - Inflammatory markers in serum and CSF - Coagulation cascade activation - ICU length of stay, ventilator days At discharge: - Hospital length of stay - Hospital disposition During follow-up at 6 months: - Modified Rankin Scale (mRS Score) - Glasgow Outcome Score extended (GOSE) - Montreal Cognitive Assessment (MoCA) - Quality of life (EQ-5D-5L) - Quality of life (SF-36) ;Timepoint(s) of evaluation of this end point: During hospitalization up to 6 months follow-up | — |
Countries
Netherlands
Contacts
Public ContactWouter Moojen
Haaglanden Medisch Centrum
Outcome results
None listed