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 abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients.
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 > or = 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.


CONCLUSIONS
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).
Jensen
Jens-Ulrik
JU
Dept. Of Clinical Microbiology 445, Hvidovre Hospital, Kettegård Allé 30, DK-2650, Hvidovre, Denmark. koordinator@pass-studiet.dk
Lundgren
Bettina
B
Hein
Lars
L
Mohr
Thomas
T
Petersen
Pernille L
PL
Andersen
Lasse H
LH
Lauritsen
Anne O
AO
Hougaard
Sine
S
Mantoni
Teit
T
Bømler
Bonnie
B
Thornberg
Klaus J
KJ
Thormar
Katrin
K
Løken
Jesper
J
Steensen
Morten
M
Carl
Peder
P
Petersen
J Asger
JA
Tousi
Hamid
H
Søe-Jensen
Peter
P
Bestle
Morten
M
Hestad
Søren
S
Andersen
Mads H
MH
Fjeldborg
Paul
P
Larsen
Kim M
KM
Rossau
Charlotte
C
Thomsen
Carsten B
CB
Ostergaard
Christian
C
Kjaer
Jesper
J
Grarup
Jesper
J
Lundgren
Jens D
JD
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D011498:Protein Precursors / Q000097:blood*; D018805:Sepsis / Q000175:diagnosis* / Q000401:mortality
D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide