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

Leiden University Medical Center (LUMC)

Status and phase: Enrolling; Phase 2

Conditions: Trauma, Head; Traumatic Brain Injury

Treatments: Drug: C1 Inhibitor, Human; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04489160

NL7255105823

Details and patient eligibility

About

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.

Enrollment: 106 estimated patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No 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;

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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106 participants in 2 patient groups, including a placebo group

C1-inhibitor

Experimental group

Description:

One dose 6000 IU C1-inhibitor intravenously

Treatment:

Drug: C1 Inhibitor, Human

Placebo

Placebo Comparator group

Description:

0.9% saline

Treatment:

Drug: Placebo