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

Sponsor

Leiden University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04489160

Collaborator

Netherlands Brain Foundation (Other), Takeda (Industry)

106

Enrollment

Locations

Arms

40.1

Anticipated Duration (Months)

35.3

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury Trauma, Head	Drug: C1 Inhibitor, Human Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

106 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial on the Safety and Efficacy of C1 Inhibitor for the Acute Management of Severe Traumatic Brain Injury

Actual Study Start Date :

Feb 25, 2021

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: C1-inhibitor One dose 6000 IU C1-inhibitor intravenously	Drug: C1 Inhibitor, Human 6000 IU C1-INH Other Names: Cinryze
Placebo Comparator: Placebo 0.9% saline	Drug: Placebo 0.9% saline

Arm

Intervention/Treatment

Experimental: C1-inhibitor

One dose 6000 IU C1-inhibitor intravenously

Drug: C1 Inhibitor, Human

6000 IU C1-INH

Other Names:

Cinryze

Placebo Comparator: Placebo

0.9% saline

Drug: Placebo

0.9% saline

Outcome Measures

Primary Outcome Measures

Therapy Intensity Level (TIL) Scale [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) [At 6 months after trauma]
Functional outcome (minimum score = 1, maximum score = 8)
Complication rate [Up to 1 year]
Adverse and serious adverse events related possibly related to study medication

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;