Clinical trial NCT06359782: Complement Inhibition: Attacking the Overshooting Inflammation @Fter Subarachnoid Hemorrhage (CIAO@SAH)
Official title: A Phase II Trial on the Safety and Efficacy of C1 Inhibitor for the Acute Management of Subarachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Lead sponsor: Haaglanden Medical Centre
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
name: Takeda
First posted: 2024-04-11
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective, multicenter, randomized, double-blind, placebo-controlled, phase II trial.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with delayed cerebral ischemia (DCI)
timeFrame: To be determined between day 4 and day 14 of admission
measure: Number of participants with complications during hospitalization.
timeFrame: Up to 1 year after admission
Secondary outcomes:
measure: Number of participants with cerebral infarction on brain CT
timeFrame: at 14 days after admission
measure: Number of participants dying
timeFrame: Up to 1 year after admission
measure: Neurological condition measured by Glasgow Coma Scale
timeFrame: During the first 14 days
measure: Complement activity markers measured in serum and CSF
timeFrame: Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration
measure: Inflammatory markers measured in serum and CSF
timeFrame: Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration
measure: Number of days in the hospital
timeFrame: Up to 1 year
measure: Number of ICU days
timeFrame: Up to 1 year
measure: Number of ventilator days
timeFrame: Up to 1 year
measure: Clinical outcome
timeFrame: At 6 months
measure: Clinical outcome
timeFrame: At 6 months
measure: Clinical outcome
timeFrame: At 6 months
measure: Clinical outcome
timeFrame: At 6 months
measure: Clinical outcome
timeFrame: At 6 months
Other outcomes:
Locations:
city: Den Haag
country: Netherlands
facility: Haaglanden Medical Centre
state: Zuid Holland
Study officials:
affiliation: Haaglanden Medisch Centrum
name: Wouter Moojen, MD PHD
role: PRINCIPAL_INVESTIGATOR
References: