Back to resultsComplement Inhibition: Attacking the Overshooting Inflammation @Fter Traumatic Brain Injury (CIAO@TBI)
Primary Purpose
Traumatic Brain Injury, Trauma, Head
Status
Recruiting
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
C1 Inhibitor, Human
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Traumatic Brain Injury focused on measuring Traumatic Brain Injury, C1-inhibitor, Neuroinflammation, Efficacy, Safety
Eligibility Criteria
Inclusion Criteria:
- 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;
Exclusion Criteria:
- 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.
Sites / Locations
- Haaglanden Medisch CentrumRecruiting
- Leiden University Medical CenterRecruiting
- Erasmus Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
C1-inhibitor
Placebo
Arm Description
One dose 6000 IU C1-inhibitor intravenously
0.9% saline
Outcomes
Primary Outcome Measures
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)
Glasgow Outcome Scale Extended (GOSE)
Functional outcome (minimum score = 1, maximum score = 8)
Complication rate
Adverse and serious adverse events related possibly related to study medication
Secondary Outcome Measures
Intracranial pressure (ICP) burden
Minutes of ICP>20 mm Hg
CT scan midline shift
in mm
Mortality
Glasgow Outcome Scale Extended (GOSE)
Functional outcome (minimum score = 1, maximum score = 8)
QoLiBri
Quality of Life
SF-36
Health-related quality of life
EQ-5D-5L
Health-related quality of life
ICU length of stay
in days
Ventilator days
in days
Hospital length of stay
in days
Hospital disposition
Discharged to home, rehabilitation or nursery home
UCH-L1 and GFAP biomarkers
Complement activation
WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50
Coagulation cascade activation
PT, aPPT, PLT, D-dimer, fibrinogen
Inflammatory markers
TNF-alpha, intraleukins
Full Information
NCT ID
NCT04489160
First Posted
July 17, 2020
Last Updated
September 6, 2021
Sponsor
Leiden University Medical Center
Collaborators
Netherlands Brain Foundation, Takeda
1. Study Identification
Unique Protocol Identification Number
NCT04489160
Brief Title
Complement Inhibition: Attacking the Overshooting Inflammation @Fter Traumatic Brain Injury
Acronym
CIAO@TBI
Official Title
A Phase II Trial on the Safety and Efficacy of C1 Inhibitor for the Acute Management of Severe Traumatic Brain Injury
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Recruiting
Study Start Date
February 25, 2021 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center
Collaborators
Netherlands Brain Foundation, Takeda
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury, Trauma, Head
Keywords
Traumatic Brain Injury, C1-inhibitor, Neuroinflammation, Efficacy, Safety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
106 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
C1-inhibitor
Arm Type
Experimental
Arm Description
One dose 6000 IU C1-inhibitor intravenously
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0.9% saline
Intervention Type
Drug
Intervention Name(s)
C1 Inhibitor, Human
Other Intervention Name(s)
Cinryze
Intervention Description
6000 IU C1-INH
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0.9% saline
Primary Outcome Measure Information:
Title
Therapy Intensity Level (TIL) Scale
Description
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)
Time Frame
First four ICU days
Title
Glasgow Outcome Scale Extended (GOSE)
Description
Functional outcome (minimum score = 1, maximum score = 8)
Time Frame
At 6 months after trauma
Title
Complication rate
Description
Adverse and serious adverse events related possibly related to study medication
Time Frame
Up to 1 year
Secondary Outcome Measure Information:
Title
Intracranial pressure (ICP) burden
Description
Minutes of ICP>20 mm Hg
Time Frame
First four ICU days
Title
CT scan midline shift
Description
in mm
Time Frame
Up to 1 year
Title
Mortality
Time Frame
Up to 1 year after trauma
Title
Glasgow Outcome Scale Extended (GOSE)
Description
Functional outcome (minimum score = 1, maximum score = 8)
Time Frame
At discharge (an average of 14 days), 3 and 12 months after trauma
Title
QoLiBri
Description
Quality of Life
Time Frame
At 3, 6 and 12 months after trauma
Title
SF-36
Description
Health-related quality of life
Time Frame
At 3, 6 and 12 months after trauma
Title
EQ-5D-5L
Description
Health-related quality of life
Time Frame
At 6 and 12 months after trauma
Title
ICU length of stay
Description
in days
Time Frame
Up to 1 year
Title
Ventilator days
Description
in days
Time Frame
Up to 1 year
Title
Hospital length of stay
Description
in days
Time Frame
Up to 1 year
Title
Hospital disposition
Description
Discharged to home, rehabilitation or nursery home
Time Frame
Up to 1 year
Title
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
Title
Complement activation
Description
WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50
Time Frame
Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Title
Coagulation cascade activation
Description
PT, aPPT, PLT, D-dimer, fibrinogen
Time Frame
Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Title
Inflammatory markers
Description
TNF-alpha, intraleukins
Time Frame
Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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;
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Inge van Erp, BSc
Phone
+31(0)715262109
Email
i.a.m.van_erp@lumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wilco Peul, MD, MPH, PhD, MBa
Organizational Affiliation
Leiden University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Haaglanden Medisch Centrum
City
Den Haag
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wilco Peul
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wilco Peul
Facility Name
Erasmus Medical Center
City
Rotterdam
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wilco Peul
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24489093
Citation
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.
Results Reference
background
PubMed Identifier
34863258
Citation
van 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.
Results Reference
derived
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Complement Inhibition: Attacking the Overshooting Inflammation @Fter Traumatic Brain Injury
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