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

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

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.

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.