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

NCT ID: NCT04489160

Last Updated: 2021-09-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-25
• Study Completion Date: 2024-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

C1-inhibitor

One dose 6000 IU C1-inhibitor intravenously

Group Type: EXPERIMENTAL

C1 Inhibitor, Human

Intervention Type: DRUG

6000 IU C1-INH

Placebo

0.9% saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.9% saline

Interventions

C1 Inhibitor, Human

6000 IU C1-INH

Intervention Type: DRUG

Placebo

0.9% saline

Intervention Type: DRUG

Other Intervention Names

Cinryze

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Netherlands Brain Foundation

OTHER

Sponsor Role: collaborator

Takeda

INDUSTRY

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

wcpeul

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wilco Peul, MD, MPH, PhD, MBa

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Leiden University Medical Center

Leiden, , Netherlands

Site Status: RECRUITING

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status: NOT_YET_RECRUITING

Haaglanden Medisch Centrum

The Hague, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Inge van Erp, BSc

Role: CONTACT

i.a.m.van_erp@lumc.nl

+31(0)715262109

Facility Contacts

Wilco Peul

Role: primary

Wilco Peul

Role: primary

Wilco Peul

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 24489093 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34863258 (View on PubMed)

Other Identifiers

NL7255105823

Identifier Type: -

Identifier Source: org_study_id