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

Phase 2

• Conditions: Trauma, Head; Traumatic Brain Injury
• Interventions: Drug: C1 Inhibitor, Human; Drug: Placebo

• Registration Number: NCT04489160
• Lead Sponsor: Leiden University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-17
• Study First Submitted QC: 2020-07-24
• Study First Posted: 2020-07-28
• Study Start: 2021-02-25
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-06
• Last Update Posted: 2021-09-13
• Primary Completion: 2023-07
• Study Completion: 2024-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 106

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;

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
C1-inhibitor	C1 Inhibitor, Human	One dose 6000 IU C1-inhibitor intravenously
Placebo	Placebo	0.9% saline

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (3)

Haaglanden Medisch Centrum; 🇳🇱 Den Haag, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands