Using high quality clinical databases to complement the results of randomised controlled trials: the case of recombinant human activated protein C

Padkin, Andrew; Rowan, Kathy; Black, Nick

doi:10.1136/bmj.323.7318.923

Cited by 60 publications

(36 citation statements)

References 11 publications

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“…However, the survival is better than that reported for a large Veterans Administration study (18), for a cohort of patients from five US hospitals (17), and for a multicenter British cohort (11). Possible reasons for these differences include differences in the patient populations and differences in the use of co-interventions (11), reflecting the heterogeneity both of severe sepsis and of severe sepsis care (35,36).…”

Section: Discussionmentioning

confidence: 94%

“…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.…”

mentioning

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%

“…One key limitation noted by Padkin et al (11) and by Hinds (14) was the lack of follow-up beyond 28 days. Indeed, over 40% of subjects alive at day 28 in PROWESS were still hospitalized (15).…”

mentioning

confidence: 99%

“…Indeed, over 40% of subjects alive at day 28 in PROWESS were still hospitalized (15). Day 28 has been the typical end-point in prior sepsis trials but the few clinical and observational studies with extended follow-up (11,(16)(17)(18)(19)(20)(21) reported many subjects were hospitalized well beyond 28 days (20) and many subjects died in the following year (18,21) and beyond (17)(18)(19)21). These data prompted an international expert panel to suggest follow-up of at least 3-6 months and longer if possible (22).…”

mentioning

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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Section: Discussionmentioning

confidence: 94%

mentioning

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%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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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Human recombinant activated protein C for severe sepsis

Martí‐Carvajal

Salanti

Cardona³

2007

Cochrane Database of Systematic Reviews

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This review suggests that APC should not be used in sepsis with an APACHE II score of less than 25 or, in paediatric patients. There is very weak evidence supporting APC use in patients with severe sepsis and at high-risk of death. As a result, policy-makers, clinicians and academics should be cautious when promoting the use of APC to patients with severe sepsis and an APACHE II score of 25 or greater. There is a need for further RCTs to answer with certainty what the role of APC is for patients with severe sepsis and an APACHE II score of at least 25. Those RCTs should be designed and conducted by non-profit organizations.

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