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

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 af...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Traumatic brain injury C1-inhibitor Neuroinflammation Randomized controlled trials Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b89b282f61b84e6a94a926ddd61fe737
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spelling	oai:doaj.org-article:b89b282f61b84e6a94a926ddd61fe7372021-12-05T12:20:11ZSafety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial10.1186/s13063-021-05833-11745-6215https://doaj.org/article/b89b282f61b84e6a94a926ddd61fe7372021-12-01T00:00:00Zhttps://doi.org/10.1186/s13063-021-05833-1https://doaj.org/toc/1745-6215Abstract 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 2020-000140-58Inge A. M. van ErpThomas A. van EssenKees FluiterErik van ZwetPeter van VlietFrank BaasIain HaitsmaDagmar VerbaanBert CoertGodard C. W. de RuiterWouter A. MoojenMathieu van der JagtWilco C. PeulBMCarticleTraumatic brain injuryC1-inhibitorNeuroinflammationRandomized controlled trialsMedicine (General)R5-920ENTrials, Vol 22, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Traumatic brain injury C1-inhibitor Neuroinflammation Randomized controlled trials Medicine (General) R5-920
spellingShingle	Traumatic brain injury C1-inhibitor Neuroinflammation Randomized controlled trials Medicine (General) R5-920 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 Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial
description	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
format	article
author	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
author_facet	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
author_sort	Inge A. M. van Erp
title	Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial
title_short	Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial
title_full	Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial
title_fullStr	Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial
title_full_unstemmed	Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial
title_sort	safety and efficacy of c1-inhibitor in traumatic brain injury (ciao@tbi): study protocol for a randomized, placebo-controlled, multi-center trial
publisher	BMC
publishDate	2021
url	https://doaj.org/article/b89b282f61b84e6a94a926ddd61fe737
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Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial

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