Assessing the Use of Activated Protein C in the Treatment of Severe Sepsis

Siegel, Jay P.

doi:10.1056/nejmsb021512

Cited by 121 publications

(78 citation statements)

References 6 publications

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“…Notably, these agencies generally suggested restricting use to sicker patients. For example, the US FDA recommended use in patients with high severity of illness determined, for example, by a high APACHE II (10) score.There are, however, important limitations to the PROWESS trial (11)(12)(13)(14). One key limitation noted by Padkin et al (11) and by Hinds (14) was the lack of follow-up beyond 28 days.…”

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confidence: 99%

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The effect of drotrecogin alfa (activated) on long-term survival after severe sepsis *

Angus

Laterre

Helterbrand

et al. 2004

Critical Care Medicine

124

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Objective-To determine long-term survival for subjects with severe sepsis enrolled in the previous multicenter trial (PROWESS) of drotrecogin alfa (activated) [DrotAA] versus placebo.Address for correspondence: Derek C. Angus, MB, ChB, MPH, 604 Scaife Hall, Critical Care Medicine, University of Pittsburgh, 3550 Terrace, Pittsburgh, PA 15261, Tel: (412) 647 8110, Fax: (412) 647 3791, angusdc@ccm.upmc.edu. AUTHORSHIP ROLES Dr Angus, a lead investigator for the long-term follow-up study, was involved in all phases of the study and wrote the manuscript. Dr Laterre, a lead investigator for the long-term follow-up study, participated in the design and conduct of the study, provided review and interpretation of the results, and provided critical review of drafts of the manuscript. Dr Helterbrand participated in the design and conduct of the study, performed the statistical analysis, provided interpretation of the results, contributed to the writing of the manuscript, and provided critical review of drafts of the manuscript. Dr Ely participated in the review and interpretation of the results, and provided critical review of drafts of the manuscript. Mr. Ball participated in the design and conduct of the study, provided review and interpretation of the results, contributed to the writing of the manuscript, and provided critical review of drafts of the manuscript. Dr Garg participated in the design and conduct of the study, provided review and interpretation of the results, contributed to the writing of the manuscript, and provided critical review of drafts of the manuscript. Dr Weissfeld participated in the statistical review and interpretation of the results, and provided critical review of drafts of the manuscript. Dr Bernard was the principal investigator of the PROWESS trial that enrolled and treated all of the subjects studied additionally here. Dr Bernard also participated in the review and interpretation of the long-term follow-up results, and provided critical review of drafts of the manuscript. FINANCIAL SUPPORT AND POTENTIAL CONFLICT OF INTEREST Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptDesign-Retrospective, cross-sectional, blinded follow-up of subjects enrolled in a previous randomized, controlled trial.Setting-164 tertiary care institutions in 11 countries.Interventions-DrotAA (n=850), 24 μg/kg/h for 96 hours, or placebo (n=840).Participants-The 1690 subjects with severe sepsis enrolled and treated with study drug in PROWESS, of whom 1220 were alive at 28 days (the end of the original PROWESS follow-up). Measurements and MainResults-Long-term survival data were collected. We had followup information on 100% of subjects at 28 days, 98% at hospital discharge, 94% at 3 months, and 93% at 1 year. The longest follow-up was 3.6 years. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptDrotAA for the treatment of adults with severe sepsis. Notably, these agencies generally suggested restricting use to sicker patients. For example, the US FDA recommended use ...

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confidence: 99%

“…There are, however, important limitations to the PROWESS trial (11)(12)(13)(14). One key limitation noted by Padkin et al (11) and by Hinds (14) was the lack of follow-up beyond 28 days.…”

mentioning

confidence: 99%

The effect of drotrecogin alfa (activated) on long-term survival after severe sepsis *

Angus

Laterre

Helterbrand

et al. 2004

Critical Care Medicine

124

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“…The PROWESS study was terminated early for efficacy after both a protocol alteration and a modification in the production of the drug compound occurred midtrial. 5,6 Despite these factors, Xigris was approved by the Food and Drug Administration (FDA) under the following conditions: 1) that it be used only in patients with severe sepsis (an APACHE II score . 25) and 2) follow-up data on the efficacy and safety were to be supported by Eli Lilly, the manufacturer.…”

Section: The Xigris Storymentioning

confidence: 99%

Sepsis update: management of severe sepsis and septic shock in the emergency department after the withdrawal of Xigris

Green

Djogovic

Howes

2012

CJEM

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“…29,30 Like serious bleeding in general, ICH was more common in open-label use, occurring in 1.5% of patients. 31,33 Therefore, it is vital to have strict adherence to exclusion criteria and familiarity with the risk factors for serious bleeding. In the PROWESS trial, after randomization, risk factors for serious bleeding included procedures and injury to vascular organs, an activated partial-thromboplastin time of more than 120 seconds, an international normalized ratio greater than 3, gastrointestinal ulceration, and development of severe thrombocytopenia (Ͻ 30,000/ mm 3 ) 29 ; in a 2002 study of 2786 APC recipients, ICH was largely confined to patients with meningitis or a platelet count less than 30,000/mm 3 .…”

Section: Activated Protein Cmentioning

confidence: 99%