Drotrecogin alfa (activated) for the treatment of severe sepsis and septic shock

American Journal of the Medical Sciences

Volumn 328, Issue 4, 2004, Pages 205-214

  Rice, Todd W ^a   Bernard, Gordon R ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Activated protein C; Cost effectiveness; Drotrecogin alfa (activated); Early treatment; XIGRIS

Indexed keywords

ACETYLSALICYLIC ACID; ACTIVATED PROTEIN C; ANTITHROMBOCYTIC AGENT; CARVEDILOL; DIPYRIDAMOLE; DROTRECOGIN; FLUDROCORTISONE; HYDROCORTISONE; SIMVASTATIN; STREPTOKINASE; TICLOPIDINE; TISSUE PLASMINOGEN ACTIVATOR;

ANTICOAGULATION; ANTIINFLAMMATORY ACTIVITY; BLEEDING; BLOOD CLOTTING DISORDER; BRAIN HEMORRHAGE; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; DRUG MECHANISM; FIBRINOLYSIS; HUMAN; INFLAMMATION; INTENSIVE CARE UNIT; MICROTHROMBUS; MORBIDITY; MORTALITY; MULTIPLE ORGAN FAILURE; REVIEW; SEPSIS; SEPTIC SHOCK;

EID: 5644298607     PISSN: 00029629     EISSN: None     Source Type: Journal    
DOI: 10.1097/00000441-200410000-00003     Document Type: Article

References (72)

1. Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546-54.
2. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303-10.
3. Weycker D, Akhras KS, Edelsberg J, et al. Long-term mortality and medical care charges in patients with severe sepsis. Crit Care Med 2003;31:2316-23.
4. Matthay M. Severe sepsis-a new treatment with both anticoagulant and anti-inflammatory properties. N Engl J Med 2001;344:759-62.
5. Gilles J. FDA approves first drug for severe sepsis. Washington Post. 11/22/01, p. A05.
6. Zeni F, Freeman B, Natanson C. Antiinflammatory therapies to treat sepsis and septic shock: a reassessment [editorial]. Crit Care Med 1997;25:1095-100.
7. Warren HS, Suffredini AF, Eichacker PQ, et al. Risks and benefits of activated protein C treatment for severe sepsis. N Engl J Med 2002;347:1027-30.
8. Assman SF, Pocock SJ, Enos LE, et al. Subgroup analysis and other (mis)uses of baseline data in clinical trials. Lancet 2000;355:1064-9.
9. van der Poll T, van Deventer SJH. Cytokines and anticytokines in the pathogenesis of sepsis. Infect Dis Clin North Am 1999;13:413-26.
10. Aird WC. Vascular bed-specific hemostasis: role of endothelium in sepsis pathogenesis. Crit Care Med 2001;29(suppl 7):28-35.
11. Rosenberg RD, Aird WC. Vascular-bed-specific hemostasis and hypercoagulable states. N Engl J Med 1999;340:1555-64.
12. 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;290:238-47.
13. Warren BL, Eid A, Singer P, et al. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001;286:1869-78.
14. ten Cate H. Pathophysiology of disseminated intravascular coagulation in sepsis. Crit Care Med 2000;28:9-11.
15. Bajzar L, Nesheim ME, Tracy PB. The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent. Blood 1996;88:2093-2100.
16. Hoffmann G, Totzke G, Seibel M, et al. In vitro modulation of inducible nitric oxide synthase gene expression and nitric oxide synthesis by procalcitonin. Crit Care Med 2001;29:112-6.
17. Schmidt-Supprian M, Murphy C, While B, et al. Activated protein C inhibits tumor necrosis factor and macrophage migration inhibitory factor production in monocytes. Eur Cytokine Netw 2000;11:407-13.
18. Grinnell BW, Hermann RB, Yan SB. Human protein C inhibits selectin-mediated cell adhesion: role of unique fucosylated oligosaccharide. Glycobiol 1994;4:221-5.
19. Molino M, Woolkalis MJ, Reavey-Cantwell J, et al. Endothelial cell thrombin receptors and PAR-2. J Biol Chem 1997;272:11133-41.
20. Christman JW, Sadikot RT, Blackwell TS. The role of nuclear factor-kappa B in pulmonary disease. Chest 2000;117:1482-7.
21. Joyce DE, Gelbert L, Ciaccia A, et al. Gene expression profile of antithrombotic protein C defines new mechanisms modulating inflammation and apoptosis. J Biol Chem 2001;276:11199-203.
22. Yan SB, Dhainaut JF. Activated protein C versus protein C in severe sepsis. Crit Care Med 2001;29:S69-74.
23. Esmon C. The protein C pathway. Crit Care Med 2000;28(Suppl):S44-8.
24. Taylor FB Jr, Chang A, Esmon CT, et al. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 1987;79:918-25.
25. Murakami K, Okajima K, Uchiba M, et al. Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production. Am J Physiol 1997;272: L197-202.
26. Taylor FB, Chang ACK, Peer GT. DEGR-factor Xa blocks disseminated intravascular coagulation initiated by E coli without preventing shock or organ damage. Blood 1991;78:364-8.
27. Randolph MM, White GL, Kosanke SD. Attenuation of tissue thrombosis and hemorrhage by ala-TFPI does not account for its protection against E. coli: a comparative study of treated and untreated non-surviving baboons challenged with LD100 E. coli. Thromb Haemost 1998;79:1048-53.
28. Isobe H, Okajima K, Uchiba M, et al. Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting excessive production of nitric oxide. Circulation 2001;104:1171-5.
29. Bernard GR, Wheeler AP, Russell JA, et al., for the Ibuprofen in Sepsis Study Group. The effects of ibuprofen on the physiology and survival of patients with sepsis. N Engl J Med 1997;336:912-8.
30. 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.
31. Hesselvik JF, Malm J, Dahlback B, et al. Protein C, protein S, C4b-binding protein in severe infection and septic shock. Thomb Haemost 1991;65:126-9.
32. Leclerc F, Hazelzet J, Jude B, et al. Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. Int Care Med 1992;18:202-5.
33. Powars D, Larsen R, Johnson J, et al. Epidemic meningococcemia and purpura fulminans with induced protein C deficiency. Clin Infect Dis 1993;17:254-61.
34. Yan SB, Helterbrand JD, Hartman DL, et al. Low levels of protein C are associated with poor outcomes in severe sepsis. Chest 2001;120:915-22.
35. Mesters RM, Helterbrand J, Utterback BG, et al. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications. Crit Care Med 2000;28:2209-16.
36. Macias WL, Nelson DR. Severe protein C deficiency predicts early death in severe sepsis. Crit Care Med 2004;32(Suppl):S223-8.
37. Matthay MA, Ware LB. Plasma protein C levels in patients with acute lung injury: prognostic significance. Crit Care Med 2004;32(Suppl):S229-32.
38. Bernard GR, Wright TJ, Ely EW, et al., for the rhAPC Sepsis Study Group. Safety and dose-relationship of recombinant human activated protein C (rhAPC) on coagulopathy in severe sepsis. Crit Care Med 2001;29:2051-9.
39. Ely EW, Bernard GR, Vincent JL. Activated protein C for severe sepsis. [letter to the editor]. N Engl J Med 2002;347:1035-6.
40. FDA briefing document for XIGRIS™ for the treatment of severe sepsis. Eli Lilly and Company. September, 2001. Available at: http://www.fda.gov/ohrms/dockets/ac/O1/briefing/3797b1_02_FDAbriefing.pdf. Accessed Sept. 7, 2004.
41. Hack CE, De Groot ER, Felt-Bersma RJ, et al. Increased plasma level of interleukin-6 in sepsis. Blood 1989;74:1704-10.
42. Calandra T, Gerain J, Heumann D, et al., for The Swiss-Dutch J5 Immunoglobulin Study Group. High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. Am J Med 1991;91:23-9.
43. Bernard GR. Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis. Crit Care Med 2003;31(Suppl):S85-93.
44. Lan KKG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika 1983;70:659-63.
45. Bernard GR, Macias WL, Joyce DE, et al. Safety assessment of drotrecogin alfa (activated) in the treatment of adult patients with severe sepsis. Crit Care 2003;7:155-63.
46. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-71.
47. Landry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1997;95:1122-5.
48. Vincent JL, Angus DC, Artigas A, et al., for the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group. Effects of drotrecogin (alfa) activated on organ dysfunction in the PROWESS trial. Crit Care Med 2003;31:834-40.
49. Murakami K, Okajima K, Uchiba M, et al. Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production. Am J Physiol 1997;272: L197-202.
50. Dolovich LR, Ginsberg JS, Douketis JD, et al. A metaanalysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism. Arch Intern Med 2000;160:181-8.
51. Griffin JH, Fernandez JA, Liu D, et al. Activated protein C and ischemic stroke. Crit Care Med 2004;32(Suppl):S247-53.
52. Folsom AR, Rosamond WD, Shahar E, et al. Prospective study of markers of hemostatic function with risk of ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation 1999;100:736-42.
53. Ely EW, Laterre PF, Angus DC et al., for the PROWESS Investigators. Drotrecogin alfa (activated) administration across clinically important subgroups of patients with severe sepsis. Crit Care Med 2003;31:12-9.
54. Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-29.
55. Vincent JL, Sundin DP, Trzaskoma BL, et al. Change in first day vasopressor use is predictive of outcome in severe sepsis, regardless of steroid use. Crit Care Med 2003;12(Suppl):A116.
56. Levy MM, Macias WL, Russell JA, et al. Failure to improve during first day of therapy is predictive of 28-day mortality in severe sepsis. Chest 2003;124(Suppl):120S.
57. Wheeler AP, Steingrub J, Linde-Zwirble W, et al. Prompt administration of drotrecogin alfa (activated) is associated with improved survival. Crit Care Med 2003;12(Suppl):A120.
58. Schmidt G, Bates B, McCollam JS, et al. Clinical use of drotrecogin alfa (activated): patients treated in mercury differ from those in prowess. Crit Care Med 2003;12(Suppl): A116.
59. Wheeler AP, Doig C, Wright T, et al. Baseline characteristics and survival of adult severe sepsis patients treated with drotrecogin alfa (activated) in a global, single-arm, open-label trial (ENHANCE). Chest 2003;124(Suppl):91S.
60. Vincent JL, Levy MM, Macias WL, et al. Early intervention with drotrecogin alfa (activated) improves survival benefit. Crit Care Med 2003;12(Suppl):A123.
61. Business Week. Available at: http://www.businessweek. com/bwdaily/dnflash/mar2002/nf2002037_2428.htm. Accessed Sept. 7, 2002.
62. Antiplatelet Trialists Collaboration. Collaborative overview of randomised trials of antiplatelet therapy. I. Prevention of death, myocardial infarction and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994;308:81-106.
63. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9.
64. Cannon CP, Braunwald E, McCabe CH, et al., for the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-504.
65. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure: US Carvedilol Heart Failure Study Group. N Engl J Med 1996;334:1349-55.
66. National Highway Traffic Safety Administration. Effectiveness of occupant protection systems and their use. Third report to Congress. Washington, DC: National Highway Traffic Safety Administration, US Dept of Transportation; 1996.
67. Kadish A, Dyer A, Daubert JP, et al., for the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004;350:2151-8.
68. Anonymous. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. (GISSI). Lancet 1986;1:397-402.
69. Anonymous. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349-60.
70. Anonymous. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction (GUSTO). N Engl J Med 1993;329:673-82.
71. Angus DC, Linde-Zwirble WT, Clermont G, et al. Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis. Crit Care Med 2003;31:1-11.
72. Coughlin MT, Angus DC. Economic evaluation of new therapies in critical illness. Crit Care Med 31(Suppl 1):S7-16, 2003.