Traumatic Brain InjuryPhase 2CIAO@TBINCT04489160
Complement Inhibition: Attacking the Overshooting Inflammation @Fter Traumatic Brain Injury
A Phase 2 study testing C1 Inhibitor, Human in people with Traumatic Brain Injury and Trauma, Head, run by Leiden University Medical Center at 3 sites in Netherlands.
Trial summary
Severe Traumatic Brain Injury (s-TBI) is a major cause of death and disability across all ages. Besides the primary impact, the pathophysiologic process of major secondary brain damage consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Traumatic Brain Injury, Trauma, Head
- What is being tested?
- C1 Inhibitor, Human
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 3 sitesNetherlands
- Study dates
- 25 Feb 2021to Jul 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age at admission ≥ 18 years and < 65 years;
- Clinical diagnosis of traumatic brain injury with GCS < 13 (with intracranial deviations);
- Catheter placement for monitoring and management of increased ICP for at least 24 hours;
Who cannot join
- A clear, non-traumatic cause of low GCS (e.g. toxic, cardial) on admission;
- Not expected to survive more than 24 hours after admission;
- Brain death on arrival in the participating centers;
- Severe pre-trauma disability, defined as being dependent on other people;
- Known prior history of sensibility to blood products or Cinryze;
- Patients with a history of hereditary angioedema;
- Patients with a history of thrombosis;
- Pregnant women.
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites, 3 recruiting
- Recruiting
Leiden University Medical Center
Leiden
Wilco Peul
- Not yet recruiting
Erasmus Medical Center
Rotterdam
Wilco Peul
- Recruiting
Haaglanden Medisch Centrum
The Hague
Wilco Peul
About this study
Official title: A Phase II Trial on the Safety and Efficacy of C1 Inhibitor for the Acute Management of Severe Traumatic Brain Injury
Severe Traumatic Brain Injury (s-TBI) is a major cause of death and disability across all ages. Besides the primary impact, the pathophysiologic process of major secondary brain damage consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system is therefore considered to be a potentially important new treatment for TBI, as has been shown in animal studies. This trial aims to study the safety and efficacy of C1-inhibitor compared to placebo in TBI patients. By temporarily blocking the complement system we hypothesize limitation of secondary brain injury and more favourable clinical outcome for TBI patients due to a decrease in the posttraumatic neuroinflammatory response.
- Conditions
- Traumatic Brain Injury, Trauma, Head
- Being tested
- C1 Inhibitor, Human, Placebo
- Keywords
- Traumatic Brain Injury, C1-inhibitor, Neuroinflammation, Efficacy, Safety
- Medical subject headings
- Brain Injuries, Traumatic, Craniocerebral Trauma, Angioedemas, Hereditary, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1 Inhibitor, HumanDrug
Also called Cinryze
6000 IU C1-INH
PlaceboDrug
0.9% saline
| Study group | Role | What they receive |
|---|---|---|
| C1-inhibitor | Experimental | One dose 6000 IU C1-inhibitor intravenously Receives: Drug: C1 Inhibitor, Human |
| Placebo | Placebo comparator | 0.9% saline Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Therapy Intensity Level (TIL) Scale
TIL differentiated for various treatment modalities aimed at prevention or control of raised Intracranial Pressure (ICP) and/or for CPP management (0 to 38 points)
Measured: First four ICU days
Glasgow Outcome Scale Extended (GOSE)
Functional outcome (minimum score = 1, maximum score = 8)
Measured: At 6 months after trauma
Complication rate
Adverse and serious adverse events related possibly related to study medication
Measured: Up to 1 year
Secondary outcomes (15)
Intracranial pressure (ICP) burden
Minutes of ICP>20 mm Hg
Measured: First four ICU days
CT scan midline shift
in mm
Measured: Up to 1 year
Mortality
Measured: Up to 1 year after trauma
Glasgow Outcome Scale Extended (GOSE)
Functional outcome (minimum score = 1, maximum score = 8)
Measured: At discharge (an average of 14 days), 3 and 12 months after trauma
QoLiBri
Quality of Life
Measured: At 3, 6 and 12 months after trauma
SF-36
Health-related quality of life
Measured: At 3, 6 and 12 months after trauma
EQ-5D-5L
Health-related quality of life
Measured: At 6 and 12 months after trauma
ICU length of stay
in days
Measured: Up to 1 year
Ventilator days
in days
Measured: Up to 1 year
Hospital length of stay
in days
Measured: Up to 1 year
Hospital disposition
Discharged to home, rehabilitation or nursery home
Measured: Up to 1 year
UCH-L1 and GFAP biomarkers
Measured: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Complement activation
WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50
Measured: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Coagulation cascade activation
PT, aPPT, PLT, D-dimer, fibrinogen
Measured: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Inflammatory markers
TNF-alpha, intraleukins
Measured: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2020
- Study start25 Feb 2021
- Primary completionJul 2023 (estimated)
- Study completionJul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Brain Foundation, Takeda
- Responsible party
- Principal investigator, wcpeul, Leiden University Medical Center
- Investigators
- Wilco Peul, MD, MPH, PhD, MBa, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04489160
- Sponsor's protocol ID
- NL7255105823
- Acronym
- CIAO@TBI
- Status last verified
- Sep 2021
- First submitted
- 17 Jul 2020
- Last updated
- 13 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fluiter K, Opperhuizen AL, Morgan BP, Baas F, Ramaglia V. Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice. J Immunol. 2014 Mar 1;192(5):2339-48. doi: 10.4049/jimmunol.1302793. Epub 2014 Jan 31.
PubMed 24489093van Erp IAM, van Essen TA, Fluiter K, van Zwet E, van Vliet P, Baas F, Haitsma I, Verbaan D, Coert B, de Ruiter GCW, Moojen WA, van der Jagt M, Peul WC. Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial. Trials. 2021 Dec 4;22(1):874. doi: 10.1186/s13063-021-05833-1.
PubMed 34863258
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2021. 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 Severe Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT04489160
- Acronym / sponsor ID
- CIAO@TBI / NL7255105823
- Conditions
- Traumatic Brain Injury, Trauma, Head
- Keywords
- Traumatic Brain Injury, C1-inhibitor, Neuroinflammation, Efficacy, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 106 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Netherlands Brain Foundation, Takeda
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 28 Jul 2020 (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.
Severe Traumatic Brain Injury (s-TBI) is a major cause of death and disability across all ages. Besides the primary impact, the pathophysiologic process of major secondary brain damage consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system is therefore considered to be a potentially important new treatment for TBI, as has been shown in animal studies. This trial aims to study the safety and efficacy of C1-inhibitor compared to placebo in TBI patients. By temporarily blocking the complement system we hypothesize limitation of secondary brain injury and more favourable clinical outcome for TBI patients due to a decrease in the posttraumatic neuroinflammatory 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
| Arm | Type | Receives |
|---|---|---|
| C1-inhibitor | Experimental | Drug: C1 Inhibitor, HumanOne dose 6000 IU C1-inhibitor intravenously |
| Placebo | Placebo comparator | Drug: Placebo0.9% saline |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age at admission ≥ 18 years and < 65 years;
- Clinical diagnosis of traumatic brain injury with GCS < 13 (with intracranial deviations);
- Catheter placement for monitoring and management of increased ICP for at least 24 hours;
Key exclusion criteria (8 listed)
- A clear, non-traumatic cause of low GCS (e.g. toxic, cardial) on admission;
- Not expected to survive more than 24 hours after admission;
- Brain death on arrival in the participating centers;
- Severe pre-trauma disability, defined as being dependent on other people;
- Known prior history of sensibility to blood products or Cinryze;
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 Inhibitor, HumanAlso: Cinryze6000 IU C1-INH | Drug | C1-inhibitor |
| Placebo0.9% saline | Drug | Placebo |
Primary outcome
Therapy Intensity Level (TIL) Scale
Time frame: First four ICU days
TIL differentiated for various treatment modalities aimed at prevention or control of raised Intracranial Pressure (ICP) and/or for CPP management (0 to 38 points)
Glasgow Outcome Scale Extended (GOSE)
Time frame: At 6 months after trauma
Functional outcome (minimum score = 1, maximum score = 8)
Complication rate
Time frame: Up to 1 year
Adverse and serious adverse events related possibly related to study medication
15 secondary outcomes
Intracranial pressure (ICP) burden
Time frame: First four ICU days
CT scan midline shift
Time frame: Up to 1 year
Mortality
Time frame: Up to 1 year after trauma
Glasgow Outcome Scale Extended (GOSE)
Time frame: At discharge (an average of 14 days), 3 and 12 months after trauma
QoLiBri
Time frame: At 3, 6 and 12 months after trauma
SF-36
Time frame: At 3, 6 and 12 months after trauma
EQ-5D-5L
Time frame: At 6 and 12 months after trauma
ICU length of stay
Time frame: Up to 1 year
Ventilator days
Time frame: Up to 1 year
Hospital length of stay
Time frame: Up to 1 year
Hospital disposition
Time frame: Up to 1 year
UCH-L1 and GFAP biomarkers
Time frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Complement activation
Time frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Coagulation cascade activation
Time frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Inflammatory markers
Time frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2021.
- Background: PubMed 24489093Fluiter K, Opperhuizen AL, Morgan BP, Baas F, Ramaglia V. Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice. J Immunol. 2014 Mar 1;192(5):2339-48. doi: 10.4049/jimmunol.1302793. Epub 2014 Jan 31.
- Derived from this study: PubMed 34863258van Erp IAM, van Essen TA, Fluiter K, van Zwet E, van Vliet P, Baas F, Haitsma I, Verbaan D, Coert B, de Ruiter GCW, Moojen WA, van der Jagt M, Peul WC. Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial. Trials. 2021 Dec 4;22(1):874. doi: 10.1186/s13063-021-05833-1.
- 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. This study is not recruiting at the moment.
Wilco Peul, MD, MPH, PhD, MBa principal investigator
Leiden University Medical Center
3 sites 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 Inhibitor, Human in people with Traumatic Brain Injury and Trauma, Head, run by Leiden University Medical Center at 3 sites 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: status not confirmed, as of the sponsor's last update on 13 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Inge van Erp, BSc (+31(0)715262109, i.a.m.van_erp@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Therapy Intensity Level (TIL) Scale (time frame: First four ICU days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04489160, which also lists 2 linked publications.
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 13 Sep 2021.