Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial

Inge A.M. van Erp*, Thomas A. van Essen, Kees Fluiter, Erik van Zwet, Peter van Vliet, Frank Baas, Iain Haitsma, Dagmar Verbaan, Bert Coert, Godard C.W. de Ruiter, Wouter A. Moojen, Mathieu van der Jagt, Wilco C. Peul

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
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Abstract

Background: Traumatic brain injury (TBI) is a major cause of death and disability across all ages. After the primary impact, the pathophysiologic process of secondary brain injury 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 could therefore be a therapeutic target in TBI. Objective: To study the safety and efficacy of C1-inhibitor (C1-INH) compared to placebo in patients with TBI. By temporarily blocking the complement system, we hypothesize a decrease in the posttraumatic neuroinflammatory response resulting in a less unfavorable clinical outcome for TBI patients. Methods: CIAO@TBI is a multicenter, randomized, blinded, phase II placebo-controlled trial. Adult TBI patients with GCS < 13 requiring intracranial pressure (ICP) monitoring will be randomized, using block randomization, within 12 h after trauma to one dose 6000 IU C1-INH or placebo. A total of 106 patients will be included, and follow-up will occur up to 12 months. The primary endpoints are (1) Therapy Intensity Level (TIL) Scale, (2) Glasgow Outcome Scale-Extended (GOSE) at 6 months, and (3) complication rate during hospitalization. Outcomes will be determined by a trial nurse blinded for the treatment allocation. Analyses will be conducted in an intention-to-treat analysis. Discussion: We expect that C1-INH administration will be safe and potentially effective to improve clinical outcomes by reducing neuroinflammation in TBI patients. Trial registration: ClinicalTrials.gov NCT04489160. Registered on 27 July 2020. EudraCT 2020-000140-58.

Original languageEnglish
Article number874
JournalTrials
Volume22
Issue number1
DOIs
Publication statusPublished - 4 Dec 2021

Bibliographical note

Funding Information:
This project is financially funded by the Hersenstichting Nederland (Dutch Brain Foundation, grant number DR-2019-00292). Takeda Development Center Americas, Inc. funds by providing the trial intervention (Request ID: IIR-NLD-002790). The funding bodies have no role in the design of the study; collection, management, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication.

Publisher Copyright:
© 2021, The Author(s).

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