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| Name | Class |
|---|---|
| Leiden University Medical Center | OTHER |
| Takeda | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| C1-esterase inhibitor (Cinryze) | Experimental | One group receiving study medication (C1-esterase inhibitor Cinryze) |
|
| Placebo | Placebo Comparator | One group receiving placebo medication |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| C1 Esterase Inhibitor Injection [Cinryze] | Drug | C1 Esterase Inhibitor Injection [Cinryze] |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Number of participants with complications during hospitalization. | Complication rate during hospitalization | Up to 1 year after admission |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with cerebral infarction on brain CT | at 14 days after admission | |
| Number of participants dying | Mortality rate | Up to 1 year after admission |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Daan de Groot, MD | Contact | 088 979 7900 | daan.de.groot@haaglandenmc.nl |
| Name | Affiliation | Role |
|---|---|---|
| Wouter Moojen, MD PHD | Haaglanden Medisch Centrum | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Haaglanden Medical Centre | Recruiting | The Hague | South Holland | 2512HH | Netherlands |
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| ID | Term |
|---|---|
| D013345 | Subarachnoid Hemorrhage |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D050718 | Complement C1 Inhibitor Protein |
| C469952 | SERPING1 protein, human |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D003174 | Complement C1 Inactivator Proteins |
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A prospective, multicenter, randomized, double-blind, placebo-controlled, phase II trial.
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| Placebo | Drug | Sodium Chloride /physiological saline (0.9%) in equal volume dosed intravenous |
|
| 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 |
| 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 |
| 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 |
| Number of days in the hospital | Hospital length of stay | Up to 1 year |
| Number of ICU days | ICU length of stay | Up to 1 year |
| Number of ventilator days | Ventilator days | Up to 1 year |
| Clinical outcome | Modified Ranking Scale, minimum value 0, maximum value 6, higher score means worse outcome | At 6 months |
| Clinical outcome | Glasgow Outcome Scale Extended, minimum value 1, maximum value 8, higher score means better outcome | At 6 months |
| Clinical outcome | Barthel Index, minimum value 0, maximum value 100, higher score means better outcome | At 6 months |
| Clinical outcome | Montreal Cognitive assessment, minimum value 0, maximum value 30, higher score means better outcome | At 6 months |
| Clinical outcome | Quality of Life (EQ-5D-5l), minimum value -0.51, maximum value 1, higher score means better outcome | At 6 months |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D015843 |
| Serpins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D003169 | Complement Inactivator Proteins |
| D003165 | Complement System Proteins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |