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Am J Respir Crit Care Med. 2011 Jun 1;183(11):1561-8. doi: 10.1164/rccm.201007-1167OC. Epub 2011 Feb 4.

Recombinant tissue factor pathway inhibitor in severe community-acquired pneumonia: a randomized trial.

Collaborators (185)

Albertson T, Anderson L, Baird I, Dal Nogare A, DeMatte-D'Amico J, Iregui M, Jauregui-Peredo L, Kinasewitz G, Laos L, Chisdak M, Matuschak G, Morris P, Park M, Simpson S, Preston J, Seibert A, Stone J, Doig C, Chittock D, Hebert P, Muscedere J, Light B, Jacka M, Mehta S, Poirier G, Wood G, Russell J, Krumpe P, Siegel M, Willms D, Tessler S, Hammersley J, Paunovic B, Stimpson R, Cheng E, Levy M, Almoosa K, Hirsch G, St John R, Ferguson N, Fowler R, Silver M, Reyno J, Shanholtz C, Scheinberg P, Keenan S, Neff M, Legare M, Albert M, Kutsogiannis D, Marsh J, DeMarini T, Bruton C, Wright P, Barker R, Swilley J, Hoo GS, Conrad S, Kazemi M, Lewis F, Witty L, Martin J, Snyder D, Marshall J, DePietro M, Feldman G, Pullman J, Klausner H, Quaranta AJ, Boscia J, Fletcher EC, Fletcher E, Ganesh S, Dean N, Taylor R, Anzueto A, Hodder R, Amin D, Schuller D, Botnick WC, Koura FA, Sepulveda P, Alapat P, Schroeder E, Emery D, Cohen J, Chang S, Hector Gentile J, San Juan J, Corral J, Prieto S, Jasovich A, Margareth SA, Moritz R, Patelli Lima M, Rocha M, Fiterman J, Mohamad Youssef NC, Cysneiros T, Reis C, Goncxalves Macedo A, Casa de Santos S, Alcantara Holanda M, Delgado Barros Pereira E, Reyes W, Chahín Anania C, Barker C, Isabel M, Villaran Ferreyros C, Cesar Muñoz Sanchez J, Vivar Mendoza A, Genaro J, Camere Torrealva MA, de Carvalho Rezende EA, Richards B, French C, Woolfe C, Turner A, Hourigan C, Cade J, Newell S, Dobb G, Leditschke IA, Peake S, Seppelt I, Henderson S, Williams A, Ernest D, van Heerden P, Bellomo R, Wright G, Freebairn R, Garrett P, Morrison L, Dugernier T, Forët F, Benoit D, Dive A, Lambermont B, Quinonez M, Spapen H, van der Rest P, Malbrain M, Peckelsen C, Álvarez-Lerma F, Artigas A, Tejerina E, Ibáñez J, Manuel Nava J, Santos A, Torrabadella P, Torres A, Sánchez García M, Desachy A, Capellier G, Carlet J, Francxois B, Offenstadt G, Perrotin D, Reignier, Ruyer O, Sollet JP, Bohe J, Mercat A, van der Berg PS, Hendrick J, van Rensburg J, Lalloo U, Richards G, Poulose V, Loo CM, Mukhopadhyay A, Kim WJ, Hwang SC, Jung KS, Sohn JW, Cho YK, Kim JH, Kim HY, Tai LL, Kamaliah L, Mustafa M, Tan CC, Hassan J, Diaz D.

Author information

1
Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. r-wunderink@northwestern.edu

Abstract

RATIONALE:

Severe community-acquired pneumonia (sCAP) is a leading cause of death worldwide. Adjunctive therapies for sCAP are needed to further improve outcome. A systemic inhibitor of coagulation, tifacogin (recombinant human tissue factor pathway inhibitor) seemed to provide mortality benefit in the sCAP subgroup of a previous sepsis trial.

OBJECTIVES:

Evaluate the impact of adjunctive tifacogin on mortality in patients with sCAP.

METHODS:

A multicenter, randomized, placebo-controlled, double-blind, three-arm study was conducted from July 2005 to June 2008 at 188 centers in North and South America, Europe, South Africa, Asia, Australia, and New Zealand. Adults with sCAP were randomized to receive a continuous intravenous infusion of tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, or matching placebo over 96 hours.

MEASUREMENTS AND MAIN RESULTS:

Severity-adjusted 28-day all-cause mortality. Of 2,138 randomized patients, 946, 238, and 918 received tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, and placebo, respectively. Tifacogin 0.075 mg/kg/h was discontinued after the first interim analysis according to prespecified futility criterion. The 28-day all-cause mortality rates were similar between the 0.025 mg/kg/h (18%) and placebo groups (17.9%) (P = 0.56). Greater reduction in prothrombin fragment 1+2 and thrombin antithrombin complexes levels relative to baseline throughout the first 96 hours was found with tifacogin 0.025 mg/kg/h than with placebo. The incidence of adverse events and serious adverse events were comparable between the tifacogin 0.025 mg/kg/h and placebo groups.

CONCLUSIONS:

Tifacogin showed no mortality benefit in patients with sCAP despite evidence of biologic activity.

PMID:
21297074
DOI:
10.1164/rccm.201007-1167OC
[Indexed for MEDLINE]

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