Evaluating the efficacy and safety of two doses of the polyclonal anti-tumor necrosis factor-α Fragment antibody AZD9773 in Adult patients with severe sepsis and/or septic shock: Randomized, double-blind, placebo-controlled phase IIb Study

Critical Care Medicine

Volumn 42, Issue 3, 2014, Pages 504-511

  Bernard, Gordon R ^a   Francois, Bruno ^b   Mira, Jean Paul ^c   Vincent, Jean Louis ^d   Dellinger, R Phillip ^e   Russell, James A ^f   Larosa, Steven P ^g   Laterre, Pierre Francois ^h   Levy, Mitchell M ⁱ   Dankner, Wayne ^j   Schmitt, Nicola ^k   Lindemann, Justin ^k,l   Wittebole, Xavier ^h  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^b DUPUYTREN UNIVERSITY HOSPITAL   (France)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d CNRS   (France)

^e ERASME HOSPITAL   (Belgium)

^f Department of Anesthesiology   (United States)

^g UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^h Beverly Hospital   (United States)

ⁱ CLINIQUES UNIVERSITAIRES SAINT LUC   (Belgium)

^j BROWN UNIVERSITY   (United States)

^k PAREXEL INTERNATIONAL   (United States)

^l ASTRAZENECA   (United Kingdom)

more..

Author keywords

intensive care; phase II; polyclonal; randomized controlled trial; sepsis; tumor necrosis factor

Indexed keywords

ADULT; AGED; CONFIDENCE INTERVALS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; EVALUATION STUDIES AS TOPIC; FEMALE; FOLLOW-UP STUDIES; HUMANS; IMMUNOGLOBULIN FAB FRAGMENTS; INFUSIONS, INTRAVENOUS; KAPLAN-MEIER ESTIMATE; MALE; MIDDLE AGED; RISK ASSESSMENT; SEPSIS; SHOCK, SEPTIC; STATISTICS, NONPARAMETRIC; SURVIVAL RATE; TREATMENT OUTCOME; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84894456331     PISSN: 00903493     EISSN: 15300293     Source Type: Journal    
DOI: 10.1097/CCM.0000000000000043     Document Type: Article

References (29)

1. Dombrovskiy VY, Martin AA, Sunderram J, et al: Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: A trend analysis from 1993 to 2003. Crit Care Med 2007; 35:1244-1250
2. Dellinger RP, Levy MM, Carlet JM, et al; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine: Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296-327
3. Bone RC, Fisher CJ Jr, Clemmer TP, et al: Sepsis syndrome: A valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med 1989; 17:389-393
4. van der Poll T, van Deventer SJ: Cytokines and anticytokines in the pathogenesis of sepsis. Infect Dis Clin North Am 1999; 13:413-426, ix
5. Thijs LG, Hack CE: Time course of cytokine levels in sepsis. Intensive Care Med 1995; 21(Suppl 2):S258-S263
6. Antonopoulou A, Giamarellos-Bourboulis EJ: Immunomodulation in sepsis: State of the art and future perspective. Immunotherapy 2011; 3:117-128
7. Qiu P, Cui X, Barochia A, et al: The evolving experience with therapeutic TNF inhibition in sepsis: Considering the potential influence of risk of death. Expert Opin Investig Drugs 2011; 20:1555-1564
8. Nelson PN, Reynolds GM, Waldron EE, et al: Monoclonal antibodies. Mol Pathol 2000; 53:111-117
9. Covell DG, Barbet J, Holton OD, et al: Pharmacokinetics of monoclonal immunoglobulin G1, F(ab?)2, and Fab? in mice. Cancer Res 1986; 46:3969-3978
10. Schaumann W, Kaufmann B, Neubert P, et al: Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication. Eur J Clin Pharmacol 1986; 30:527-533
11. Rice TW, Wheeler AP, Morris PE, et al: Safety and efficacy of affinity-purified, anti-tumor necrosis factor-Alpha, ovine fab for injection (CytoFab) in severe sepsis. Crit Care Med 2006; 34:2271-2281
12. Morris PE, Zeno B, Bernard AC, et al: A placebo-controlled, double-blind, dose-escalation study to assess the safety, tolerability and pharmacokinetics/pharmacodynamics of single and multiple intravenous infusions of AZD9773 in patients with severe sepsis and septic shock. Crit Care 2012; 16:R31
13. AstraZeneca: Global Policy: Bioethics. 2011. Available at: http://www.astrazeneca.com/Responsibility/Code-policies-standards/ Ourglobal-policies. Accessed April 12, 2013
14. Fisher CJ Jr, Opal SM, Dhainaut JF, et al: Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. The CB0006 Sepsis Syndrome Study Group. Crit Care Med 1993; 21:318-327
15. Abraham E, Glauser MP, Butler T, et al: p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. Ro 45-2081 Study Group. JAMA 1997; 277:1531-1538
16. Abraham E, Anzueto A, Gutierrez G, et al: Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group. Lancet 1998; 351:929-933
17. Nguyen HB, Loomba M, Yang JJ, et al: Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock. J Inflamm (Lond) 2010; 7:6
18. Rivers EP, Kruse JA, Jacobsen G, et al: The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med 2007; 35:2016-2024
19. The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301-1308
20. Ranieri VM, Suter PM, Tortorella C, et al: Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: A randomized controlled trial. JAMA 1999; 282:54-61
21. Fisher CJ Jr, Agosti JM, Opal SM, et al: Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med 1996; 334:1697-1702
22. Ranieri VM, Thompson BT, Barie PS, et al; PROWESS-SHOCK Study Group: Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012; 366:2055-2064
23. Aggenix AG: Agennix Halts Phase II/III OASIS Trial in Severe Sepsis, 2012. Available at: http://www.agennix.com/index.php?option=com- content&view=article&id=43&Itemid=53&lang=en. Accessed April 12, 2013
24. Artisan Pharma Inc: Summary of ART-123 Global Phase 2b Study. 2012. Available at: http://www.akpamerica.com/120606-MARK-Summary-of-Global-Ph2b- study%200531.pdf. Accessed December 5, 2013
25. Ferrer R, Artigas A, Levy MM, et al; Edusepsis Study Group: Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA 2008; 299:2294-2303
26. Ferrer R, Artigas A: Effectiveness of treatments for severe sepsis: Data from the bundle implementation programs. Minerva Anestesiol 2011; 77:360-365
27. Gao F, Melody T, Daniels DF, et al: The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: A prospective observational study. Crit Care 2005; 9:R764-R770
28. Levy MM, Dellinger RP, Townsend SR, et al; Surviving Sepsis Campaign: The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010; 38:367-374
29. Micek ST, Roubinian N, Heuring T, et al: Before-After study of a standardized hospital order set for the management of septic shock. Crit Care Med 2006; 34:2707-2713