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A clinical evaluation committee assessment of recombinant human tissue factor pathway inhibitor (Tifacogin) in patients with severe community-acquired pneumonia.
Crit Care. 2009 Mar 15;13(2):R36
Authors: Laterre PF, Opal SM, Abraham E, Larosa SP, Creasey AA, Xie F, Poole L, Wunderink RG
ABSTRACT: INTRODUCTION: To determine the potential efficacy of recombinant human tissue factor pathway inhibitor (tifacogin) in a subpopulation of patients with community-acquired pneumonia (CAP) from a Phase III study of severe sepsis. METHODS: Retrospective review of patients with suspected pneumonia conducted by an independent clinical evaluation committee (CEC) blinded to treatment assignment. The CEC re-analyzed data from patients enrolled in an international multi-center clinical trial of sepsis who had a diagnosis of pneumonia as probable source of sepsis. The primary efficacy measure was all-cause 28-day mortality. RESULTS: Of 847 patients identified on case report forms with a clinical diagnosis of pneumonia, the CEC confirmed 780 cases (92%) as pneumonia. Of confirmed pneumonia cases, 496 (63.6%) met the definition for CAP. In the CEC CAP population, the mortality rates of the tifacogin and the placebo groups were 70/251 (27.9%) and 80/245 (32.7%), respectively. The strongest signals were seen in patients with CAP not receiving concomitant heparin, having microbiologically confirmed infection, or the combination of documented infection and no heparin. The reduction in mortality in this narrowly defined subgroup when treated with tifacogin compared with placebo was statistically significant (17/58, 29.3% with tifacogin and 28/54, 51.9% with placebo, unadjusted p-value < 0.02). CONCLUSIONS: Tifacogin administration did not significantly reduce mortality in all severe CAP patients. Exploratory analyses showed an improved survival in patients who did not receive concomitant heparin with microbiologically-confirmed infections. These data support the rationale of an ongoing Phase III study exploring the potential benefit of tifacogin in severe CAP (ClinicalTrials.gov identifier NCT00084071).
PMID: 19284881 [PubMed - as supplied by publisher]