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

Haaglanden Medical Centre

Status and phase: Enrolling; Phase 2

Conditions: Subarachnoid Hemorrhage, Aneurysmal

Treatments: Drug: Placebo; Drug: C1 Esterase Inhibitor Injection [Cinryze]

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06359782

NL76082.058.20

Details and patient eligibility

About

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.

Enrollment: 128 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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128 participants in 2 patient groups, including a placebo group

C1-esterase inhibitor (Cinryze)

Experimental group

Description:

One group receiving study medication (C1-esterase inhibitor Cinryze)

Treatment:

Drug: C1 Esterase Inhibitor Injection [Cinryze]

Placebo

Placebo Comparator group

Description:

One group receiving placebo medication

Treatment:

Drug: Placebo