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

NCT04489160 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: NL7255105823
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 3

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.

Conditions

Traumatic Brain Injury; Trauma, Head

Keywords

Traumatic Brain Injury; C1-inhibitor; Neuroinflammation; Efficacy; Safety

Outcome Measures

Primary Outcomes (3)

• 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

• Glasgow Outcome Scale Extended (GOSE)

  Functional outcome (minimum score = 1, maximum score = 8)

  At 6 months after trauma

• Complication rate

  Adverse and serious adverse events related possibly related to study medication

  Up to 1 year

Secondary Outcomes (15)

• Intracranial pressure (ICP) burden

  First four ICU days

• CT scan midline shift

  Up to 1 year

• 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

• QoLiBri

  At 3, 6 and 12 months after trauma

Study Arms (2)

C1-inhibitor

EXPERIMENTAL

One dose 6000 IU C1-inhibitor intravenously

Drug: C1 Inhibitor, Human

Placebo

PLACEBO COMPARATOR

0.9% saline

Drug: Placebo

Interventions

C1 Inhibitor, Human DRUG

6000 IU C1-INH

Also known as: Cinryze

C1-inhibitor

Placebo DRUG

0.9% saline

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Netherlands Brain Foundation: collaborator
• Takeda: collaborator

Study Sites (3)

Leiden University Medical Center

Leiden, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, Netherlands

NOT YET RECRUITING

Haaglanden Medisch Centrum

The Hague, Netherlands

RECRUITING

Related Publications (2)

• 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.

  PMID: 24489093 BACKGROUND

• 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.

  PMID: 34863258 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Craniocerebral Trauma; Angioedemas, Hereditary; Neuroinflammatory Diseases

Interventions

SERPING1 protein, human

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wilco Peul, MD, MPH, PhD, MBa

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Inge van Erp, BSc

CONTACT

+31(0)715262109; i.a.m.van_erp@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 28, 2020
• Study Start: February 25, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2024
• Last Updated: September 13, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)