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Annals of Intensive Care
Published in: Annals of Intensive Care 1/2016

Open Access 01-12-2016 | Research

Design and conduct of the activated protein C and corticosteroids for human septic shock (APROCCHSS) trial

Authors: Djillali Annane, Christian Brun Buisson, Alain Cariou, Claude Martin, Benoit Misset, Alain Renault, Blandine Lehmann, Valérie Millul, Virginie Maxime, Eric Bellissant, The APROCCHSS Investigators for the TRIGGERSEP Network

Published in: Annals of Intensive Care | Issue 1/2016

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Abstract

Background

We aimed at assessing the benefit-to-risk ratio of activated protein C (drotrecogin-alfa activated, DAA) and corticosteroids, given alone or in combination, in patients with septic shock.

Methods

We implemented an investigator-led, publicly funded, multicenter, randomized according to a 2 × 2 factorial design, placebo-controlled, double-blind trial in four parallel groups in which adults with persistent septic shock and no contraindication to DAA were assigned to either DAA alone (24 mg/kg/h for 96 h), or hydrocortisone (50 mg intravenous bolus q6 for 7 days) and fludrocortisone (50 µg once daily through the nasogastric tube for 7 days) alone, or their respective combinations, or their respective placebos. Primary endpoint was 90-day mortality rate. Follow-up duration was 6 months. Statistical analysis was planned to be performed in intent-to-treat once after all participants completed 180-day follow-up and according to the 2 × 2 factorial design.

Results

The first patient was recruited in September 2008. The trial was suspended on October 25, 2011, owing to the withdrawal from the market of DAA. At this time, 411 patients had been enrolled. On May 17, 2012, the continuation of the trial on two parallel groups was approved by all legal authorities with the aim of investigating the benefit-to-risk ratio of corticosteroids. On June 30, 2014, the trial was suspended again by the study sponsor upon request of the independent data and safety monitoring board. Recruitment restarted on October 7, 2014, after any safety concern was ruled out. Finally, the trial was completed on June 23, 2015, with the recruitment of 1241 patients.

Conclusions

This report details the design, statistical plan and conduct of a randomized controlled trial of hydrocortisone and fludrocortisone in septic shock.
Trial registration The trial was registered at ClinicalTrials.gov under NCT00625209
Appendix
Available only for authorised users
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Metadata
Title
Design and conduct of the activated protein C and corticosteroids for human septic shock (APROCCHSS) trial
Authors
Djillali Annane
Christian Brun Buisson
Alain Cariou
Claude Martin
Benoit Misset
Alain Renault
Blandine Lehmann
Valérie Millul
Virginie Maxime
Eric Bellissant
The APROCCHSS Investigators for the TRIGGERSEP Network
Publication date
01-12-2016
Publisher
Springer Paris
Published in
Annals of Intensive Care / Issue 1/2016
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-016-0147-3

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