The difficulties of clinical trials evaluating therapeutic agents in patients with severe sepsis

Irish Journal of Medical Science

Volumn 181, Issue 1, 2012, Pages 1-6

  Hall, T C ^a   Bilku, D K ^a   Al Leswas, D ^a   Horst, C ^b   Dennison, A R ^a  

^a LEICESTER GENERAL HOSPITAL   (United Kingdom)

^b UNIVERSITY HOSPITALS OF LEICESTER NHS TRUST   (United Kingdom)

Author keywords

Clinical trials; Review; Sepsis; Therapeutic agents

Indexed keywords

ETANERCEPT;

CLINICAL TRIAL (TOPIC); CRITICALLY ILL PATIENT; DATA ANALYSIS; DISEASE MODEL; DISEASE SEVERITY; GENETIC ASSOCIATION; GRAM NEGATIVE SEPSIS; GRAM POSITIVE INFECTION; GRAM POSITIVE SEPSIS; HUMAN; INTENTION TO TREAT ANALYSIS; NONHUMAN; PATIENT SELECTION; REVIEW; SAMPLE SIZE; SEPSIS; SEPTIC SHOCK;

CLINICAL TRIALS AS TOPIC; HUMANS; RESEARCH DESIGN; SEPSIS;

EID: 84863003002     PISSN: 00211265     EISSN: 18634362     Source Type: Journal    
DOI: 10.1007/s11845-011-0778-1     Document Type: Review

References (48)

1. Vincent JL, Sakr Y, Sprung CL et al (2006) Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 34(2):344-353 (Pubitemid 43145611)
2. Harrison DA, Welch CA, Eddleston JM (2006) The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database. Crit Care 10(2):R42
3. Dellinger RP, Levy MM, Carlet JM et al (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med 34:17-60
4. Levy MM, Dellinger RP, Townsend SR et al (2010) Surviving sepsis campaign: the Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 38:367-374
5. Opal SM (1995) Lessons learned from clinical trials of sepsis. J Endotoxin Res 2:221-226
6. Vincent JL (2004) Evidence-based medicine in the ICU: important advances and limitations. Chest 12(2):592-600
7. Vincent JL, Sun Q, Dubois MJ (2002) Clinical trials of immunomodulatory therapies in severe sepsis and septic shock. Clin Infect Dis 34:1084-1093 (Pubitemid 34289681)
8. Fisher CJ, Agosti JM Jr, Opal SM et al (1996) Treatment of septic shock by tumour necrosis factor receptor: Fc fusion protein. N Engl JMed 334:1697-1702 (Pubitemid 26193621)
9. Annane D (2000) Effects of the combination of hydrocortisone (HC)-fludrocortisone (FC) on mortality in septic shock. Crit Care Med 28:A63
10. van den Berghe G, Wouters P, Weekers F et al (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359-1367
11. Bernard GR, Vincent JL, Laterre PF et al (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699-709 (Pubitemid 32204987)
12. Sprung CL, Annane D, Keh D et al (2008) Corticus study group: hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111-124
13. Brunkhorst FM, Engel C, Bloos F et al (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125-139
14. Rowan KM, Kerr JH, Major E, Mc Pherson K, Short A, Vessey MP (1993) Intensive care society APACHE II study in Britain and Ireland II: outcome comparisons of intensive care units after adjustment for case mix by the American APACHE II method. BMJ 307:977-981 (Pubitemid 23306764)
15. Sprung CL, Eidelman LA, Pizov R et al (1997) Influence of alterations in foregoing life-sustaining treatment practices on a clinical sepsis trial. Crit Care Med 25:383-387 (Pubitemid 27152728)
16. Opal SM (2003) Clinical trial design and outcomes in patients with severe sepsis. Shock 20(4):295-302
17. Opal SM, Cohen J (1999) Clinical Gram-positive sepsis: Does it fundamentally differ from Gram-negative bacterial sepsis. Crit Care Med 27:1608-1616 (Pubitemid 29406956)
18. Bone RC (1993) Gram-negative sepsis: a dilemma of modern medicine. Clin Microbiol Rev 6:57-68 (Pubitemid 23055194)
19. Pournaras S, Iosifidis E, Roilides E (2009) Advances in antibacterial therapy against emerging bacterial pathogens. Semin Hematol 46(3):198-211
20. Bates DW, Pruess KE, Lee TH (1995) How bad are bacteremia and sepsis? Outcomes in a cohort with suspected bacteremia. Arch Intern Med 155:593-598
21. Bone RC (1994) Gram-positive organisms and sepsis. Arch Intern Med 154(1):26-34 (Pubitemid 24018098)
22. Valles J, Leon C, Alvarez-Ledrma F (1997) Nosocomial bacteremia in critically ill patients: a multicentre study evaluating epidemiology and prognosis. Clin Infect Dis 24:403-408
23. Gao H, Evans TW, Finney SJ (2008) Bench-to-bedside review: sepsis, severe sepsis and septic shock-does the nature of the infecting organism matter? Crit Care 12(3):213 Epub 2008 May 6
24. Fisher CJ, Agosti J, Opal SM et al (1996) A phase II, double-blind, randomized, clinical trial of soluble TNF receptor: Fc fusion protein in the treatment of severe sepsis. N Engl J Med 334:1697-1702
25. Cross AS, Opal SM, Sadoff JD, Gemski P (1993) Choice of bacteria in animal models of sepsis. Infect Immun 61:2741-2744
26. Andersson J, Nagy S, Bjork L, Abrams J, Holm S, Andersson U (1992) Bacterial toxin-induced cytokine production studied at the single-cell level. Immunol Rev 127:69-96
27. Westendorp RGJ, Langermans JAM, Huizinga TWJ et al (1997) Genetic influence on cytokine production and fatal meningococcal disease. Lancet 349:170-173 (Pubitemid 27039197)
28. Sørensen TI, Nielsen GG, Andersen PK, Teasdale TW (1988) Genetic and environmental influences on premature death in adult adoptees. N Engl J Med 318(12):727-732 (Pubitemid 18090256)
29. Holmes CL, Russell JA, Walley KR (2003) Genetic polymorphisms in sepsis and septic shock: role in prognosis and potential for Therapy. Chest 124:1103-1115 (Pubitemid 37123334)
30. Burt RA (1999) Genetics of host response to malaria. Int J Parasitol 29:973-979 (Pubitemid 29352338)
31. Newport MJ, Huxley CM (1996) Huston S et al.: A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med 335:1941-1949 (Pubitemid 26428218)
32. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV (1998) Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. N Engl J Med 338:640-644 (Pubitemid 28108433)
33. Bernard GR, Vincent JL, Laterre PF et al (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699-709 (Pubitemid 32204987)
34. Abraham E, Laterre PF, Garg R et al (2005) Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death: administration of drotrecogin alfa (activated) in early stage severe sepsis (ADDRESS) study group. N Engl J Med 353(13):1332-1341
35. Smedira NG, Evans BH, Grais LS et al (1990) Withholding and withdrawl of life support from the critically ill. New Eng J Med. 322:309-315 (Pubitemid 20046334)
36. Opal SM (1998) New strategies in the management of sepsis. Biomed Prog 11:52-56
37. Levy MM, Fink MP, Marshall JC et al (2003) 2001 SCCM/ ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 29:530-538
38. Pierrakos C, Vincent JL (2010) Sepsis biomarkers: a review. Critical Care 14:R15
39. Vincent JL (1997) Dear SIRS, Im sorry to say that I don't like you. Crit Care Med 25(2):372-374
40. Bossink AW, Groeneveld J, Hack CE, Thijs LG (1998) Prediction of mortality in febrile medical patients: How useful are systemic inflammatory response syndrome and sepsis criteria? Chest 113(6):1533-1541 (Pubitemid 28307156)
41. Bone RC, Fisher CJ, Clemmer TP, Slotman GJ, Metz CA, Balk RA (1989) Sepsis syndrome: A valid clinical entity. Crit Care Med 17:389-393 (Pubitemid 19136902)
42. Bone RC, Grodzin CJ, Balk RA (1997) Sepsis: a new hypothesis for the pathogenesis of the disease process. Chest 112:235-243 (Pubitemid 27343624)
43. Rubulotta F, Marshall JC, Ramsay G, Nelson D, Levy M, Williams M (2009) Predisposition, insult/infection, response, and organ dysfunction: a new model for staging severe sepsis. Crit Care Med 37(4):1329-1335
44. Predicting outcome in ICU patients. 2nd European consensus conference in intensive care medicine. Intensive Care Med. (1994) 20:390-397
45. Vincent J, De Mendonca A, Cantraine F et al (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicentre, prospective study. Working group on "sepsis related problems". Crit Care Med 26:1793-1800 (Pubitemid 28527688)
46. Opal SM, Cross AS (1999) Clinical trials for severe sepsis. Past failures, and future hopes. Infect Dis Clin North Am 13(2):285-297 (Pubitemid 29248745)
47. Brandtzaeg P, Kerrulf P, Gaustad P et al (1989) Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Infect Dis 159:195-204 (Pubitemid 19049357)
48. Warren HS, Suffredini AF, Eichacker PQ, Munford RS (2002) Risks and benefits of activated protein C treatment for severe sepsis. N Engl J Med 347:1027-1030