Complement Inhibition: Attacking the Overshooting Inflammation @Fter Traumatic Brain Injury

Traumatic Brain Injury Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04489160
• Other study ID #: NL7255105823
• Status: Recruiting
• Phase: Phase 2
• Start date: February 25, 2021
• Est. completion date: July 2024

Study information

• Verified date: September 2021
• Source: Leiden University Medical Center
• Contact: Inge van Erp, BSc
• Phone: +31(0)715262109
• Email: i.a.m.van_erp[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: July 2024
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Craniocerebral Trauma
• Trauma, Head
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Drug:
• C1 Inhibitor, Human
6000 IU C1-INH
• Placebo
0.9% saline

Locations

Country	Name	City	State
Netherlands	Haaglanden Medisch Centrum	Den Haag
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Erasmus Medical Center	Rotterdam

Sponsors (3)

Lead Sponsor	Collaborator
Leiden University Medical Center	Netherlands Brain Foundation, Takeda

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	First four ICU days
Primary	Glasgow Outcome Scale Extended (GOSE)	Functional outcome (minimum score = 1, maximum score = 8)	At 6 months after trauma
Primary	Complication rate	Adverse and serious adverse events related possibly related to study medication	Up to 1 year
Secondary	Intracranial pressure (ICP) burden	Minutes of ICP>20 mm Hg	First four ICU days
Secondary	CT scan midline shift	in mm	Up to 1 year
Secondary	Mortality		Up to 1 year after trauma
Secondary	Glasgow Outcome Scale Extended (GOSE)	Functional outcome (minimum score = 1, maximum score = 8)	At discharge (an average of 14 days), 3 and 12 months after trauma
Secondary	QoLiBri	Quality of Life	At 3, 6 and 12 months after trauma
Secondary	SF-36	Health-related quality of life	At 3, 6 and 12 months after trauma
Secondary	EQ-5D-5L	Health-related quality of life	At 6 and 12 months after trauma
Secondary	ICU length of stay	in days	Up to 1 year
Secondary	Ventilator days	in days	Up to 1 year
Secondary	Hospital length of stay	in days	Up to 1 year
Secondary	Hospital disposition	Discharged to home, rehabilitation or nursery home	Up to 1 year
Secondary	UCH-L1 and GFAP biomarkers		Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Secondary	Complement activation	WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50	Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Secondary	Coagulation cascade activation	PT, aPPT, PLT, D-dimer, fibrinogen	Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Secondary	Inflammatory markers	TNF-alpha, intraleukins	Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product