How many patients with severe sepsis are needed to confirm the efficacy of drotrecogin alfa activated? A Bayesian design.

Abstract:

OBJECTIVES:Controversies concerning the pivotal trial and negative results from other Drotrecogin alfa activated (DAA) trials have raised questions about its efficacy in severe sepsis patients. Based on all available evidence, our study aimed to respond to: (1) What is the current probability that DAA is not better than the control? If the current probability is not small, e.g. greater than 0.05, then (2) How many patients will be needed for the DAA confirmatory trial? DESIGN:We applied the Bayesian methodology to all randomized trials which tested anti-thrombotic therapies for severe sepsis. Prior distributions were defined as severe skeptic (all anti-thrombotic trials or DAA trials); moderate skeptic (anti-thrombotic trials with high risk of death); mild skeptic (DAA trials only); enthusiastic (DAA trials with high risk of death). RESULTS:The total study sample includes 7,683 patients: DAA (N = 3,143); Anti-thrombin-III (N = 2,581); tissue factor pathway inhibitor (N = 1,959). Answer 1: All current probabilities that DAA is not better than the control (except for the enthusiastic analysis) range from 0.14 to 0.48, which strongly suggest the need for a confirmatory trial. Answer 2: The number of patients necessary for the DAA confirmatory trial ranges up to 8,350 for the severe skeptic; 730-810 for moderate skeptic; 550-685 for mild skeptic; and zero for enthusiastic analysis. CONCLUSIONS:A confirmatory trial with approximately 600 patients with severe sepsis and high risk of death can provide a convincing answer for both the mild and moderate skeptic physicians concerning the efficacy of DAA in severe sepsis.

journal_name

Intensive Care Med

journal_title

Intensive care medicine

authors

Kalil AC,Sun J

doi

10.1007/s00134-008-1159-8

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

1804-11

issue

10

eissn

0342-4642

issn

1432-1238

journal_volume

34

pub_type

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