A multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial assessing safety and efficacy of active site inactivated recombinant factor VIIa in subjects with acute lung injury or acute respiratory distress syndrome

Critical Care Medicine

Volumn 37, Issue 6, 2009, Pages 1874-1880

  Vincent, Jean Louis ^a   Artigas, Antonio ^b   Petersen, Lars C ^c   Meyer, Christian ^c  

^a ERASME HOSPITAL   (Belgium)

^b HOSPITAL DE SABADELL   (Spain)

^c NOVO NORDISK A S   (Denmark)

Author keywords

Bleeding; Mortality; Outcome

Indexed keywords

D DIMER; INTERLEUKIN 6; PLACEBO; RECOMBINANT BLOOD CLOTTING FACTOR 7A; BLOOD CLOTTING FACTOR 7A; RECOMBINANT FVIIA; RECOMBINANT PROTEIN;

ACUTE LUNG INJURY; ADULT; ADULT RESPIRATORY DISTRESS SYNDROME; AGED; ARTICLE; ARTIFICIAL VENTILATION; BLEEDING; BLOOD ANALYSIS; BLOOD CHEMISTRY; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; FEMALE; HUMAN; INTENSIVE CARE UNIT; MAJOR CLINICAL STUDY; MALE; MORTALITY; MULTICENTER STUDY; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL; SCORING SYSTEM; VITAL SIGN; MIDDLE AGED;

ACUTE LUNG INJURY; ADULT; AGED; AGED, 80 AND OVER; DOUBLE-BLIND METHOD; FACTOR VIIA; FEMALE; HUMANS; MALE; MIDDLE AGED; RECOMBINANT PROTEINS; RESPIRATORY DISTRESS SYNDROME, ADULT; YOUNG ADULT;

EID: 66449108092     PISSN: 00903493     EISSN: 15300293     Source Type: Journal    
DOI: 10.1097/CCM.0b013e31819fff2c     Document Type: Article

References (29)

1. Avecillas JF, Freire AX, Arroliga AC: Clinical epidemiology of acute lung injury and acute respiratory distress syndrome: Incidence, diagnosis, and outcomes. Clin Chest Med 2006; 27:549-557
2. Montgomery BA, Stager MA, Carrico J, et al: Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1985; 132:485-491
3. Ferring M, Vincent JL: Is outcome from ARDS related to the severity of respiratory failure? Eur Respir J 1997; 10:1297-1300
4. Bersten AD, Edibam C, Hunt T, et al: Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. Am J Respir Crit Care Med 2002; 165:443-448
5. Monroe DM, Key NS: The tissue factor-factor VIIa complex: Procoagulant activity, regulation, and multitasking. J Thromb Haemost 2007; 5:1097-1105
6. Levi M, van der Poll T, ten Cate H: Tissue factor in infection and severe inflammation. Semin Thromb Hemost 2006; 32:33-39
7. Albrektsen T, Sorensen BB, Hjorto GM, et al: Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells. J Thromb Haemost 2007; 5:1588-1597
8. Rao LV, Pendurthi UR: Tissue factor-factor VIIa signaling. Arterioscler Thromb Vasc Biol 2005; 25:47-56
9. Versteeg HH, Ruf W: Emerging insights in tissue factor-dependent signaling events. Semin Thromb Hemost 2006; 32:24-32
10. Idell S: Extravascular coagulation and fibrin deposition in acute lung injury. New Horiz 1994; 2:566-574
11. Gunther A, Mosavi P, Heinemann S, et al: Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. Am J Respir Crit Care Med 2000; 161:454-462
12. Laterre PF, Wittebole X, Collienne C: Pharmacological inhibition of tissue factor. Semin Thromb Hemost 2006; 32:71-76
13. Pawlinski R, Pedersen B, Kehrle B, et al: Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model. Blood 2003; 101:3940-3947
14. Tang H, Ivanciu L, Popescu N, et al: Sepsisinduced coagulation in the baboon lung is associated with decreased tissue factor pathway inhibitor. Am J Pathol 2007; 171:1066-1077
15. Niessen F, Schaffner F, Furlan-Freguia C, et al: Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammation. Nature 2008; 452:654-658
16. Petersen LC, Freskgard P, Ezban M: Tissue factor-dependent factor VIIa signaling. Trends Cardiovasc Med 2000; 10:47-52
17. Erhardtsen E, Nilsson P, Johannessen M, et al: Pharmacokinetics and safety of FFR-rFVIIa after single doses in healthy subjects. J Clin Pharmacol 2001; 41:880-885
18. Kjalke M, Monroe DM, Hoffman M, et al: The effects of activated factor VII in a cell-based model for tissue factor-initiated coagulation. Blood Coagul Fibrinolysis 1998; 9 (Suppl 1):S21-S25
19. Welty-Wolf KE, Carraway MS, Miller DL, et al: Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons. Am J Respir Crit Care Med 2001; 164:1988-1996
20. Carraway MS, Welty-Wolf KE, Miller DL, et al: Blockade of tissue factor: Treatment for organ injury in established sepsis. Am J Respir Crit Care Med 2003; 167:1200-1209
21. Vincent JL, Moreno R, Takala J, et al: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/ failure. Intensive Care Med 1996; 22:707-710
22. Bolland K, Whitehead J: Formal approaches to safety monitoring of clinical trials in life-threatening conditions. Stat Med 2000; 19: 2899-2917
23. Amaral A, Opal SM, Vincent JL: Coagulation in sepsis. Intensive Care Med 2004; 30:1032-1040
24. Abraham E, Reinhart K, Opal S, et al: Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: A randomized controlled trial. JAMA 2003; 290:238-247
25. Eisele B, Lamy M, Thijs LG, et al: Antithrom-bin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med 1998; 24:663-672
26. Waydhas C, Nast-Kolb D, Gippner-Steppert C, et al: High-dose antithrombin III treatment of severely injured patients: Results of a prospective study. J Trauma 1998; 45:931-940
27. Warren BL, Eid A, Singer P, et al: Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: A randomized controlled trial. JAMA 2001; 286:1869-1878
28. Bernard GR, Vincent JL, Laterre PF, et al: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344:699-709
29. Welty-Wolf KE, Carraway MS, Huang YC, et al: Bacterial priming increases lung injury in gram-negative sepsis. Am J Respir Crit Care Med 1998; 158:610-619