Complement Inhibition: Attacking the Overshooting Inflammation @Fter Subarachnoid Hemorrhage (CIAO@SAH)

A Phase II Trial on the Safety and Efficacy of C1 Inhibitor for the Acute Management of Subarachnoid Hemorrhage

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.

Inclusion Criteria:

• Confirmed diagnosis of aneurysmal subarachnoid hemorrhage on CT-scan;
• Age ≥ 18 years on admission;
• WFNS grade 1-5.

Exclusion Criteria:

• 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