Aneurysmal subarachnoid hemorrhage (SAH) can lead to devastating outcomes for patients, like cognitive decline. This is caused by early brain injury (EBI) followed by delayed cerebral ischemia (DCI). Neuroinflammation, triggered by the complement system, has been investigated to be a key mediator in the pathophysiology of EBI and DCI. Inhibition of the complement system is therefore considered to be a potentially important new treatment for SAH. This trial aims to study the safety and efficacy of C1-inhibitor Cinryze, an approved inhibitor of the complement system, compared to placebo in patients with SAH. By temporarily blocking the complement system we hypothesize limitation of delayed cerebral ischemia and a more favourable clinical outcome for SAH patients due to a decrease in the inflammatory response.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
128
C1 Esterase Inhibitor Injection \[Cinryze\]
Sodium Chloride /physiological saline (0.9%) in equal volume dosed intravenous
Haaglanden Medical Centre
The Hague, South Holland, Netherlands
RECRUITINGNumber of participants with delayed cerebral ischemia (DCI)
Defined as either a new focal neurological impairment, or a decrease of at least 2 points on the Glasgow Coma Scale. 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.
Time frame: To be determined between day 4 and day 14 of admission
Number of participants with complications during hospitalization.
Complication rate during hospitalization
Time frame: Up to 1 year after admission
Number of participants with cerebral infarction on brain CT
Time frame: at 14 days after admission
Number of participants dying
Mortality rate
Time frame: Up to 1 year after admission
Neurological condition measured by Glasgow Coma Scale
Measured daily, minimum value of 3, maximal value of 15, higher scores mean a better outcome
Time frame: During the first 14 days
Complement activity markers measured in serum and CSF
WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50
Time frame: Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration
Inflammatory markers measured in serum and CSF
TNF-alpha, intraleukins
Time frame: Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration
Number of days in the hospital
Hospital length of stay
Time frame: Up to 1 year
Number of ICU days
ICU length of stay
Time frame: Up to 1 year
Number of ventilator days
Ventilator days
Time frame: Up to 1 year
Clinical outcome
Modified Ranking Scale, minimum value 0, maximum value 6, higher score means worse outcome
Time frame: At 6 months
Clinical outcome
Glasgow Outcome Scale Extended, minimum value 1, maximum value 8, higher score means better outcome
Time frame: At 6 months
Clinical outcome
Barthel Index, minimum value 0, maximum value 100, higher score means better outcome
Time frame: At 6 months
Clinical outcome
Montreal Cognitive assessment, minimum value 0, maximum value 30, higher score means better outcome
Time frame: At 6 months
Clinical outcome
Quality of Life (EQ-5D-5l), minimum value -0.51, maximum value 1, higher score means better outcome
Time frame: At 6 months
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