Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies

Laith Altaweel, Daniel Sweeney, Xizhong Cui, Amisha Barochia, Charles Natanson, Peter Q EichackerCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USAAbstract: Recombinant human activated protein C (rhAPC) was developed to reduce excessive coagulant and...

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Autores principales:	Laith Altaweel, Daniel Sweeney, Xizhong Cui, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2009
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/25811bbb6b944277b5ba7fd51db1aa93
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spelling	oai:doaj.org-article:25811bbb6b944277b5ba7fd51db1aa932021-12-02T06:06:07ZGrowing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies1177-54751177-5491https://doaj.org/article/25811bbb6b944277b5ba7fd51db1aa932009-09-01T00:00:00Zhttp://www.dovepress.com/growing-insights-into-the-potential-benefits-and-risks-of-activated-pr-a3547https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Laith Altaweel, Daniel Sweeney, Xizhong Cui, Amisha Barochia, Charles Natanson, Peter Q EichackerCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USAAbstract: Recombinant human activated protein C (rhAPC) was developed to reduce excessive coagulant and inflammatory activity during sepsis. Basic and clinical research has suggested these pathways contribute to the pathogenesis of this lethal syndrome and are inhibited by rhAPC. Based in large part on the results of a single multicenter randomized controlled trial, rhAPC was first approved in 2001 by the US Food and Drug Administration (FDA) as adjunctive therapy in septic patients with a high risk of death. This was followed closely by approval in Europe, Australia, and New Zealand. At the original FDA review of rhAPC, concerns were raised as to whether a confirmatory trial should be done before final regulatory approval because of concerns that rhAPCs bleeding risk might outweigh its potential benefit during clinical use. Since 2001, continuing basic and clinical research has further elucidated the complex role activated protein C may have in both adaptive and maladaptive responses during sepsis. Moreover, subsequent controlled trials in other types of septic patients and observational studies appear to support earlier concerns that the benefit-to-risk ratio of rhAPC may not support its clinical use. This experience has prompted additional trials presently underway, to define whether treatment with rhAPC as it was originally indicated in septic patients with persistent shock, is safe and effective. Until such trials are complete, physicians employing this agent must carefully consider which patients may be appropriate candidates for rhAPC administration.Keywords: rhAPC, treatment, sepsis Laith AltaweelDaniel SweeneyXizhong Cuiet alDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2009, Iss default, Pp 391-406 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Laith Altaweel Daniel Sweeney Xizhong Cui et al Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies
description	Laith Altaweel, Daniel Sweeney, Xizhong Cui, Amisha Barochia, Charles Natanson, Peter Q EichackerCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USAAbstract: Recombinant human activated protein C (rhAPC) was developed to reduce excessive coagulant and inflammatory activity during sepsis. Basic and clinical research has suggested these pathways contribute to the pathogenesis of this lethal syndrome and are inhibited by rhAPC. Based in large part on the results of a single multicenter randomized controlled trial, rhAPC was first approved in 2001 by the US Food and Drug Administration (FDA) as adjunctive therapy in septic patients with a high risk of death. This was followed closely by approval in Europe, Australia, and New Zealand. At the original FDA review of rhAPC, concerns were raised as to whether a confirmatory trial should be done before final regulatory approval because of concerns that rhAPCs bleeding risk might outweigh its potential benefit during clinical use. Since 2001, continuing basic and clinical research has further elucidated the complex role activated protein C may have in both adaptive and maladaptive responses during sepsis. Moreover, subsequent controlled trials in other types of septic patients and observational studies appear to support earlier concerns that the benefit-to-risk ratio of rhAPC may not support its clinical use. This experience has prompted additional trials presently underway, to define whether treatment with rhAPC as it was originally indicated in septic patients with persistent shock, is safe and effective. Until such trials are complete, physicians employing this agent must carefully consider which patients may be appropriate candidates for rhAPC administration.Keywords: rhAPC, treatment, sepsis
format	article
author	Laith Altaweel Daniel Sweeney Xizhong Cui et al
author_facet	Laith Altaweel Daniel Sweeney Xizhong Cui et al
author_sort	Laith Altaweel
title	Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies
title_short	Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies
title_full	Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies
title_fullStr	Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies
title_full_unstemmed	Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies
title_sort	growing insights into the potential benefits and risks of activated protein c administration in sepsis: a review of preclinical and clinical studies
publisher	Dove Medical Press
publishDate	2009
url	https://doaj.org/article/25811bbb6b944277b5ba7fd51db1aa93
work_keys_str_mv	AT laithaltaweel growinginsightsintothepotentialbenefitsandrisksofactivatedproteincadministrationinsepsisareviewofpreclinicalandclinicalstudies AT danielsweeney growinginsightsintothepotentialbenefitsandrisksofactivatedproteincadministrationinsepsisareviewofpreclinicalandclinicalstudies AT xizhongcui growinginsightsintothepotentialbenefitsandrisksofactivatedproteincadministrationinsepsisareviewofpreclinicalandclinicalstudies AT etal growinginsightsintothepotentialbenefitsandrisksofactivatedproteincadministrationinsepsisareviewofpreclinicalandclinicalstudies
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Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies

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