Clinical trial NCT04489160: Complement Inhibition: Attacking the Overshooting Inflammation @Fter Traumatic Brain Injury
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Traumatic Brain Injury
Trauma, Head
Keywords: Traumatic Brain Injury
C1-inhibitor
Neuroinflammation
Efficacy
Safety
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Netherlands Brain Foundation
name: Takeda
First posted: 2020-07-28
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Therapy Intensity Level (TIL) Scale
timeFrame: First four ICU days
measure: Glasgow Outcome Scale Extended (GOSE)
timeFrame: At 6 months after trauma
measure: Complication rate
timeFrame: Up to 1 year
Secondary outcomes:
measure: Intracranial pressure (ICP) burden
timeFrame: First four ICU days
measure: CT scan midline shift
timeFrame: Up to 1 year
measure: Mortality
timeFrame: Up to 1 year after trauma
measure: Glasgow Outcome Scale Extended (GOSE)
timeFrame: At discharge (an average of 14 days), 3 and 12 months after trauma
measure: QoLiBri
timeFrame: At 3, 6 and 12 months after trauma
measure: SF-36
timeFrame: At 3, 6 and 12 months after trauma
measure: EQ-5D-5L
timeFrame: At 6 and 12 months after trauma
measure: ICU length of stay
timeFrame: Up to 1 year
measure: Ventilator days
timeFrame: Up to 1 year
measure: Hospital length of stay
timeFrame: Up to 1 year
measure: Hospital disposition
timeFrame: Up to 1 year
measure: UCH-L1 and GFAP biomarkers
timeFrame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
measure: Complement activation
timeFrame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
measure: Coagulation cascade activation
timeFrame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
measure: Inflammatory markers
timeFrame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Other outcomes:
Locations:
city: Den Haag
country: Netherlands
facility: Haaglanden Medisch Centrum
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: Wilco Peul, MD, MPH, PhD, MBa
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.