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

Subarachnoid Hemorrhage, Aneurysmal Clinical Trial

— CIAO@SAH  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06359782
• Other study ID #: NL76082.058.20
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 1, 2024
• Est. completion date: February 2027

Study information

• Verified date: April 2024
• Source: Haaglanden Medical Centre
• Contact: Daan de Groot, MD
• Phone: 088 979 7900
• Email: daan.de.groot[@]haaglandenmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 128
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage
• Subarachnoid Hemorrhage, Aneurysmal

Intervention

Drug:
• C1 Esterase Inhibitor Injection [Cinryze]
C1 Esterase Inhibitor Injection [Cinryze]
• Placebo
Sodium Chloride /physiological saline (0.9%) in equal volume dosed intravenous

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Haaglanden Medical Centre	Leiden University Medical Center, Takeda

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number 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.	To be determined between day 4 and day 14 of admission
Primary	Number of participants with complications during hospitalization.	Complication rate during hospitalization	Up to 1 year after admission
Secondary	Number of participants with cerebral infarction on brain CT		at 14 days after admission
Secondary	Number of participants dying	Mortality rate	Up to 1 year after admission
Secondary	Neurological condition measured by Glasgow Coma Scale	Measured daily, minimum value of 3, maximal value of 15, higher scores mean a better outcome	During the first 14 days
Secondary	Complement activity markers measured in serum and CSF	WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50	Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration
Secondary	Inflammatory markers measured in serum and CSF	TNF-alpha, intraleukins	Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration
Secondary	Number of days in the hospital	Hospital length of stay	Up to 1 year
Secondary	Number of ICU days	ICU length of stay	Up to 1 year
Secondary	Number of ventilator days	Ventilator days	Up to 1 year
Secondary	Clinical outcome	Modified Ranking Scale, minimum value 0, maximum value 6, higher score means worse outcome	At 6 months
Secondary	Clinical outcome	Glasgow Outcome Scale Extended, minimum value 1, maximum value 8, higher score means better outcome	At 6 months
Secondary	Clinical outcome	Barthel Index, minimum value 0, maximum value 100, higher score means better outcome	At 6 months
Secondary	Clinical outcome	Montreal Cognitive assessment, minimum value 0, maximum value 30, higher score means better outcome	At 6 months
Secondary	Clinical outcome	Quality of Life (EQ-5D-5l), minimum value -0.51, maximum value 1, higher score means better outcome	At 6 months