Complement Inhibition: Attacking the Overshooting Inflammation @Fter Subarachnoid Hemorrhage (CIAO@SAH)
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal
- Interventions
- Drug: C1 Esterase Inhibitor Injection [Cinryze]Drug: Placebo
- Registration Number
- NCT06359782
- Lead Sponsor
- Haaglanden Medical Centre
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 128
- Confirmed diagnosis of aneurysmal subarachnoid hemorrhage on CT-scan;
- Age ≥ 18 years on admission;
- WFNS grade 1-5.
- Subarachnoid hemorrhage deemed most likely of 'peri mesencephalic' origin after consideration of history, clinical examination and radiological findings (including angiographic imaging); (not originated from an aneurysm and patients have by definition a favourable clinical outcome)
- Subarachnoid hemorrhage deemed most likely of post-traumatic origin after consideration of history, clinical examination and radiological findings (including angiographic imaging); (does not occur spontaneous)
- Participation in another clinical therapeutic study;
- Patients with definite infaust prognosis on arrival and/or expected death within 24 hours of admission
- 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 (when known at time of inclusion);
- Pregnant woman
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description C1-esterase inhibitor (Cinryze) C1 Esterase Inhibitor Injection [Cinryze] One group receiving study medication (C1-esterase inhibitor Cinryze) Placebo Placebo One group receiving placebo medication
- Primary Outcome Measures
Name Time Method Number of participants with delayed cerebral ischemia (DCI) To be determined between day 4 and day 14 of admission 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.
Number of participants with complications during hospitalization. Up to 1 year after admission Complication rate during hospitalization
- Secondary Outcome Measures
Name Time Method Number of participants with cerebral infarction on brain CT at 14 days after admission Number of participants dying Up to 1 year after admission Mortality rate
Neurological condition measured by Glasgow Coma Scale During the first 14 days Measured daily, minimum value of 3, maximal value of 15, higher scores mean a better outcome
Complement activity markers measured in serum and CSF Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50
Inflammatory markers measured in serum and CSF Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration TNF-alpha, intraleukins
Number of days in the hospital Up to 1 year Hospital length of stay
Number of ICU days Up to 1 year ICU length of stay
Number of ventilator days Up to 1 year Ventilator days
Clinical outcome At 6 months Quality of Life (EQ-5D-5l), minimum value -0.51, maximum value 1, higher score means better outcome
Trial Locations
- Locations (1)
Haaglanden Medical Centre
🇳🇱Den Haag, Zuid Holland, Netherlands