Subarachnoid Hemorrhage, AneurysmalPhase 2CIAO@SAHNCT06359782
Complement Inhibition: Attacking the Overshooting Inflammation @Fter Subarachnoid Hemorrhage (CIAO@SAH)
A Phase 2 study testing C1 Esterase Inhibitor Injection [Cinryze] in people with Subarachnoid Hemorrhage, Aneurysmal, run by Haaglanden Medical Centre at 1 site in Netherlands.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Subarachnoid Hemorrhage, Aneurysmal
- What is being tested?
- C1 Esterase Inhibitor Injection [Cinryze]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 1 siteNetherlands
- Study dates
- 4 Nov 2024to Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of aneurysmal subarachnoid hemorrhage on CT-scan;
- Age ≥ 18 years on admission;
- WFNS grade 1-5.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Haaglanden Medical Centre
The Hague, South Holland, 2512HH
Daan de Groot, MD, 0889797900, daan.de.groot@haaglandenmc.nl
About this study
Official title: 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.
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal
- Being tested
- C1 Esterase Inhibitor Injection [Cinryze], Placebo
- Medical subject headings
- Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1 Esterase Inhibitor Injection [Cinryze]Drug
Also called Cinryze
C1 Esterase Inhibitor Injection [Cinryze]
PlaceboDrug
Sodium Chloride /physiological saline (0.9%) in equal volume dosed intravenous
| Study group | Role | What they receive |
|---|---|---|
| C1-esterase inhibitor (Cinryze) | Experimental | One group receiving study medication (C1-esterase inhibitor Cinryze) Receives: Drug: C1 Esterase Inhibitor Injection [Cinryze] |
| Placebo | Placebo comparator | One group receiving placebo medication Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: To be determined between day 4 and day 14 of admission
Number of participants with complications during hospitalization.
Complication rate during hospitalization
Measured: Up to 1 year after admission
Secondary outcomes (13)
Number of participants with cerebral infarction on brain CT
Measured: at 14 days after admission
Number of participants dying
Mortality rate
Measured: Up to 1 year after admission
Neurological condition measured by Glasgow Coma Scale
Measured daily, minimum value of 3, maximal value of 15, higher scores mean a better outcome
Measured: During the first 14 days
Complement activity markers measured in serum and CSF
WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50
Measured: 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
Measured: 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
Measured: Up to 1 year
Number of ICU days
ICU length of stay
Measured: Up to 1 year
Number of ventilator days
Ventilator days
Measured: Up to 1 year
Clinical outcome
Modified Ranking Scale, minimum value 0, maximum value 6, higher score means worse outcome
Measured: At 6 months
Clinical outcome
Glasgow Outcome Scale Extended, minimum value 1, maximum value 8, higher score means better outcome
Measured: At 6 months
Clinical outcome
Barthel Index, minimum value 0, maximum value 100, higher score means better outcome
Measured: At 6 months
Clinical outcome
Montreal Cognitive assessment, minimum value 0, maximum value 30, higher score means better outcome
Measured: At 6 months
Clinical outcome
Quality of Life (EQ-5D-5l), minimum value -0.51, maximum value 1, higher score means better outcome
Measured: At 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2024
- Study start4 Nov 2024
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Subarachnoid Hemorrhage, AneurysmalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A prospective, multicenter, randomized, double-blind, placebo-controlled, phase II trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Haaglanden Medical Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center, Takeda
- Responsible party
- Principal investigator, Wouter Moojen, Haaglanden Medical Centre
- Investigators
- Wouter Moojen, MD PHD, Principal investigator, Haaglanden Medisch Centrum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06359782
- Sponsor's protocol ID
- NL76082.058.20
- Acronym
- CIAO@SAH
- Status last verified
- Oct 2024
- First submitted
- 22 Mar 2024
- Last updated
- 27 Dec 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial on the Safety and Efficacy of C1 Inhibitor for the Acute Management of Subarachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT06359782
- Acronym / sponsor ID
- CIAO@SAH / NL76082.058.20
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 128 participants (estimated)
- Lead sponsor
- Haaglanden Medical CentreUniversity, hospital or other
- Collaborators
- Leiden University Medical Center, Takeda
- Study start
- 4 Nov 2024 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 11 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A prospective, multicenter, randomized, double-blind, placebo-controlled, phase II trial.
| Arm | Type | Receives |
|---|---|---|
| C1-esterase inhibitor (Cinryze) | Experimental | Drug: C1 Esterase Inhibitor Injection [Cinryze]One group receiving study medication (C1-esterase inhibitor Cinryze) |
| Placebo | Placebo comparator | Drug: PlaceboOne group receiving placebo medication |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed diagnosis of aneurysmal subarachnoid hemorrhage on CT-scan;
- Age ≥ 18 years on admission;
- WFNS grade 1-5.
Key exclusion criteria (8 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| C1 Esterase Inhibitor Injection [Cinryze]Also: CinryzeC1 Esterase Inhibitor Injection [Cinryze] | Drug | C1-esterase inhibitor (Cinryze) |
| PlaceboSodium Chloride /physiological saline (0.9%) in equal volume dosed intravenous | Drug | Placebo |
Primary outcome
Number of participants with delayed cerebral ischemia (DCI)
Time frame: To be determined between day 4 and day 14 of admission
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.
Number of participants with complications during hospitalization.
Time frame: Up to 1 year after admission
Complication rate during hospitalization
13 secondary outcomes
Number of participants with cerebral infarction on brain CT
Time frame: at 14 days after admission
Number of participants dying
Time frame: Up to 1 year after admission
Neurological condition measured by Glasgow Coma Scale
Time frame: During the first 14 days
Complement activity markers measured in serum and CSF
Time frame: 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
Time frame: Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration
Number of days in the hospital
Time frame: Up to 1 year
Number of ICU days
Time frame: Up to 1 year
Number of ventilator days
Time frame: Up to 1 year
Clinical outcome
Time frame: At 6 months
Clinical outcome
Time frame: At 6 months
Clinical outcome
Time frame: At 6 months
Clinical outcome
Time frame: At 6 months
Clinical outcome
Time frame: At 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wouter Moojen, MD PHD principal investigator
Haaglanden Medisch Centrum
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing C1 Esterase Inhibitor Injection [Cinryze] in people with Subarachnoid Hemorrhage, Aneurysmal, run by Haaglanden Medical Centre at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daan de Groot, MD (088 979 7900, daan.de.groot@haaglandenmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with delayed cerebral ischemia (DCI) (time frame: To be determined between day 4 and day 14 of admission). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2024.