The Procalcitonin And Survival Study (PASS) -A Randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to ab

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• 作者：Jens-Ulrik Jensen (1) (2)
  Bettina Lundgren (1)
  Lars Hein (3)
  Thomas Mohr (3) (4)
  Pernille L Petersen (3)
  Lasse H Andersen (3)
  Anne ? Lauritsen (3)
  Sine Hougaard (3)
  Teit Mantoni (3)
  Bonnie B?mler (3)
  Klaus J Thornberg (4)
  Katrin Thormar (4)
  Jesper L?ken (5)
  Morten Steensen (5)
  Peder Carl (5)
  J Asger Petersen (5)
  Hamid Tousi (6)
  Peter S?e-Jensen (6)
  Morten Bestle (7)
  S?ren Hestad (7)
  Mads H Andersen (8)
  Paul Fjeldborg (8)
  Kim M Larsen (9)
  Charlotte Rossau (9)
  Carsten B Thomsen (10)
  Christian ?stergaard (1)
  Jesper Kj?r (2)
  Jesper Grarup (2)
  Jens D Lundgren (2)
  
• 刊名：BMC Infectious Diseases
• 出版年：2008
• 出版时间：December 2008
• 年：2008
• 卷：8
• 期：1
• 全文大小：805KB
• 参考文献：1. Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, Jimenez-Jimenez FJ, Perez-Paredes C, Ortiz-Leyba C: Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. / Crit Care Med 2003,31(12):2742-1. CrossRef
  2. Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, Sicignano A, Palazzo M, Moreno R, Boulme R, Lepage E, Le Gall R: Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. / Intensive Care Med 2002,28(2):108-1. CrossRef
  3. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C: High serum procalcitonin concentrations in patients with sepsis and infection. / Lancet 1993., 341:
  4. Chirouze C, Schuhmacher H, Rabaud C, Gil H, Khayat N, Estavoyer JM, May T, Hoen B: Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. / Clin Infect Dis 2002.,35(2):
  5. Dandona P, Nix D, Wilson MF, Aljada A, Love J, Assicot M, Bohuon C: Procalcitonin increase after endotoxin injection in normal subjects. / J Clin Endocrinol Metab 1994., 79:
  6. Lindberg M, Hole A, Johnsen H, Asberg A, Rydning A, Myrvold HE, Bjerve KS: Reference intervals for procalcitonin and C-reactive protein after major abdominal surgery. / Scand J Clin Lab Invest 2002., 62:
  7. Aouifi A, Piriou V, Blanc P, Bouvier H, Bastien O, Chiari P, Rousson R, Evans R, Lehot JJ: Effect of cardiopulmonary bypass on serum procalcitonin and C-reactive protein concentrations. / Br J Anaesth 1999., 83:
  8. Jensen JU, Heslet L, Jensen TH, Espersen K, Steffensen P, Tvede M: Procalcitonin increase in early identification of crittically ill patients at high risk of mortality. / Crit Care Med 2006, 34:10. CrossRef
  9. Wang TJ, Mort EA, Nordberg P, Chang Y, Cadigan ME, Mylott L, Ananian LV, Thompson BT, Fessler M, Warren W, Wheeler A, Jordan M, Fifer MA: A utilization management intervention to reduce unnecessary testing in the coronary care unit. / Arch Intern Med 2002,162(16):1885-0. CrossRef
  10. Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B: Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. / Lancet 2004,363(9409):600-. CrossRef
  11. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/8/91/prepub
  
• 作者单位：Jens-Ulrik Jensen (1) (2)
  Bettina Lundgren (1)
  Lars Hein (3)
  Thomas Mohr (3) (4)
  Pernille L Petersen (3)
  Lasse H Andersen (3)
  Anne ? Lauritsen (3)
  Sine Hougaard (3)
  Teit Mantoni (3)
  Bonnie B?mler (3)
  Klaus J Thornberg (4)
  Katrin Thormar (4)
  Jesper L?ken (5)
  Morten Steensen (5)
  Peder Carl (5)
  J Asger Petersen (5)
  Hamid Tousi (6)
  Peter S?e-Jensen (6)
  Morten Bestle (7)
  S?ren Hestad (7)
  Mads H Andersen (8)
  Paul Fjeldborg (8)
  Kim M Larsen (9)
  Charlotte Rossau (9)
  Carsten B Thomsen (10)
  Christian ?stergaard (1)
  Jesper Kj?r (2)
  Jesper Grarup (2)
  Jens D Lundgren (2)
  
  1. Dept. Of Clinical Microbiology 445, Hvidovre Hospital, Ketteg?rd Allé 30, DK-2650, Hvidovre, Denmark
  2. Centre for Viral Diseases/KMA, Rigshospitalet, 2100 Copenhagen ?, Denmark and Copenhagen HIV Programme, University of Copenhagen, Faculty of Health Sciences, The Panum Institute/Building 21.1, Blegdamsvej 3B, 2200, Copenhagen, N, Denmark
  3. Dept. of Intensive Care Y13, Glostrup University Hospital, Nordre Ringvej 69, DK-2600, Glostrup, Denmark
  4. Dept. of Intensive Care I-303, Gentofte University Hospital, Niels Andersens Vej 65, DK-2900, Gentofte, Denmark
  5. Dept. of Intensive Care 542, Hvidovre University Hospital, Kettegaard Alle 30, DK-2650, Hvidovre, Denmark
  6. Dept. of Intensive Care 104, Herlev University Hospital, Herlev Ringvej 75, DK-2730, Herlev, Denmark
  7. Dept. of Intensive Care, Hiller?d University Hospital, Helsevej 2, DK-3400, Hiller?d, Denmark
  8. Dept. of Intensive Care, Aarhus University Hospital Skejby, Brendstrupgaardsvej 100, DK-8200, Aarhus, N, Denmark
  9. Dept. of Intensive Care, Aarhus University Hospital ?rhus, N?rrebrogade 44, DK-8000, Aarhus, C, Denmark
  10. Dept. of Intensive Care, Roskilde University Hospital, K?gevej 7, DK-4000, Roskilde, Denmark
  

文摘

Background Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. Methods Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age ?18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent. Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. Discussion For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752).