- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00271752
The Procalcitonin and Survival Study (PASS)
The Procalcitonin and Survival Study - A Multicentre Single Blinded Randomized Controlled Trial to Investigate if Treatment Guided by Daily Procalcitonin Measurements Can Reduce Mortality in the Intensive Care Unit
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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. In the ICU, the infectious status of the patient is often difficult to assess because symptoms cannot be expressed (unconscious or sedated patients) and signs may present atypically because of immunologic incompetence and masking by the drugs given and thermo-therapy. Biological and biochemical markers of inflammation (White Blood Cells (WBC), C-reactive protein) may often be influenced by other parameters than infection, such as: trauma, surgery, other types of inflammation such as rheumatoid diseases (C-reactive protein) and gluco-corticosteroid treatment (WBC), 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.
For these reasons, in the clinical setting, it is often necessary to initiate or adjust antimicrobial therapy on an unsure ground and the relevant therapy may in some situations be delayed for important hours or even days. Specific and rapid markers of bacterial infection have been sought for use in the ICU. Mortality in critically ill patients increases gravely when Procalcitonin levels increase from day to day (own submitted, though yet unpublished data). Low PCT levels have been shown to effectively rule out sepsis.
However, no randomised controlled trials have been conducted to show if mortality in critically ill patients can be reduced by using a strategy of daily standardised Procalcitonin measurements as an early detector of serious bacterial infection. Therefore evidence is presently not sufficient to introduce daily consecutive Procalcitonin measurements to guide the diagnostic and therapeutic management of patients admitted to the ICU .
The rationale for this trial is to assess the ability of daily Procalcitonin measurements to reduce the mortality of critically ill patients.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Copenhagen
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Copenhagen NV, Copenhagen, Denmark, DK-2400
- Intensive Care Unit, Bispebjerg Hospital
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Gentofte, Copenhagen, Denmark, DK-2820
- Intensive Care Unit, KAS Gentofte
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Glostrup, Copenhagen, Denmark, DK-2600
- Intensive Care Unit, KAS Glostrup, Copenhagen University Hospital
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Herlev, Copenhagen, Denmark, DK-2730
- Intensive Care Unit, Herlev Hospital
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Hvidovre, Copenhagen, Denmark, DK-2650
- Intensive Care Unit 542, Hvidovre Hospital, Copenhagen University Hospital
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Frederiksborg County
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Hilleroed, Frederiksborg County, Denmark, DK-3400
- Intensive Care Unit, Hilleroed Sygehus
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Midtjylland
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Skejby, Århus, Midtjylland, Denmark, DK-8200
- Skejby Sygehus
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Århus, Midtjylland, Denmark, DK-8000
- Intensive Care Unit, Århus Sygehus, Nørrebrogade
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Sjælland
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Roskilde, Sjælland, Denmark, DK-4000
- Roskilde Sygehus
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Fulfilment of all of the following three criteria:
- Male or female, aged > 18 years of age.
- Admitted to the participating Intensive Care Units (ICUs) at the following hospitals: Hvidovre Hospital, Bispebjerg Hospital, Amager Hospital, Herlev Hospital, Glostrup Hospital, and Gentofte Hospital
- Ability to understand and provide written informed consent to participate in this trial; or ability to understand and provide oral informed consent in the presence of at least one impartial witness who should sign and personally date the consent form; or the subject's legally acceptable representative can understand and provide written informed consent if the subject is not capable of this because of the present mental or physical condition of the subject.
Exclusion Criteria:
A subject will NOT be eligible for inclusion in this trial if any of the following criteria apply:
- Subjects with known hyperbilirubinaemia (> 0.4 mg/ml) or hypertriglyceridaemia (> 10 g/l) since this can interfere with measurements. If subjects with unknown status on these points are included and have PCT measurements, the measuring equipment will detect these conditions.
- Subjects suffering from a blood disorder, where daily sampling of 7 ml of blood for a maximum of 28 days (210 ml distributed on 28 days) will be an inconvenience or a potential risk, which could compromise the safety of the subject.
- Subjects who are pregnant or breast feeding
The a priori probability of surviving with the normal recommended diagnostics and treatment with the presently available means to detect infections and, on the other hand, the normal diagnostics and treatment together with daily procalcitonin measurements and prompt clinical reaction should be equal.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PCT guided
Procalcitonin guided treatment of infections in the ICU.
Intervention: Intensification of antibiotics, surgery, microbiologic testing and diagnostic imaging, when Procalcitonin levels are increasing
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For every day Procalcitonin levels increase in the intervention group, antibiotics, surgery, diagnostic imaging and microbiologic testing is intensified
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Sham Comparator: Control
These patients receive "Standard of Care" which is the recommended treatment in the given ICU
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For every day Procalcitonin levels increase in the intervention group, antibiotics, surgery, diagnostic imaging and microbiologic testing is intensified
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
mortality/survival
Time Frame: 28 day
|
28 day
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
mortality/survival
Time Frame: 60 day
|
60 day
|
mortality/survival
Time Frame: 90 day
|
90 day
|
mortality/survival
Time Frame: 120 day
|
120 day
|
mortality/survival
Time Frame: 180 day
|
180 day
|
Consumption of antimicrobial chemotherapy
Time Frame: 28 day
|
28 day
|
Prevalence of complications to infection: sepsis
Time Frame: 28 day
|
28 day
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severe sepsis
Time Frame: 28 day
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28 day
|
septic shock
Time Frame: 28 day
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28 day
|
Multi Organ Dysfunction Syndrome
Time Frame: 28 day
|
28 day
|
Disseminated Intravascular Coagulation
Time Frame: 28 day
|
28 day
|
use of diagnostic imaging during admission to the ICU
Time Frame: 28 day
|
28 day
|
Quality of life post-ICU
Time Frame: 180 day
|
180 day
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Jens-Ulrik S Jensen, MD, PhD, Dept. of Clinical Microbiology, Hvidovre University Hospital & Copenhagen HIV Programme (CHIP), Faculty of Health Sciences, University of Copenhagen
Publications and helpful links
General Publications
- Holm FS, Sivapalan P, Seersholm N, Itenov TS, Christensen PH, Jensen JS. Acute Lung Injury in Critically Ill Patients: Actin-Scavenger Gelsolin Signals Prolonged Respiratory Failure. Shock. 2019 Sep;52(3):370-377. doi: 10.1097/SHK.0000000000001279.
- Jensen JS, Itenov TS, Thormar KM, Hein L, Mohr TT, Andersen MH, Loken J, Tousi H, Lundgren B, Boesen HC, Johansen ME, Ostrowski SR, Johansson PI, Grarup J, Vestbo J, Lundgren JD; Procalcitonin And Survival Study (PASS) Group. Prediction of non-recovery from ventilator-demanding acute respiratory failure, ARDS and death using lung damage biomarkers: data from a 1200-patient critical care randomized trial. Ann Intensive Care. 2016 Dec;6(1):114. doi: 10.1186/s13613-016-0212-y. Epub 2016 Nov 21.
- Johansen ME, Johansson PI, Ostrowski SR, Bestle MH, Hein L, Jensen AL, Soe-Jensen P, Andersen MH, Steensen M, Mohr T, Thormar K, Lundgren B, Cozzi-Lepri A, Lundgren JD, Jensen JU. Profound endothelial damage predicts impending organ failure and death in sepsis. Semin Thromb Hemost. 2015 Feb;41(1):16-25. doi: 10.1055/s-0034-1398377. Epub 2015 Jan 15.
- Johansen ME, Jensen JU, Bestle MH, Hein L, Lauritsen AO, Tousi H, Larsen KM, Loken J, Mohr T, Thormar K, Johansson PI, Cozzi-Lepri A, Lundgren JD. The potential of antimicrobials to induce thrombocytopenia in critically ill patients: data from a randomized controlled trial. PLoS One. 2013 Nov 28;8(11):e81477. doi: 10.1371/journal.pone.0081477. eCollection 2013.
- Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr T, Andersen MH, Thornberg KJ, Loken J, Steensen M, Fox Z, Tousi H, Soe-Jensen P, Lauritsen AO, Strange DG, Reiter N, Thormar K, Fjeldborg PC, Larsen KM, Drenck NE, Johansen ME, Nielsen LR, Ostergaard C, Kjaer J, Grarup J, Lundgren JD; Procalcitonin And Survival Study (PASS) Group. Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial. BMJ Open. 2012 Mar 11;2(2):e000635. doi: 10.1136/bmjopen-2011-000635. Print 2012.
- Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, Thornberg KJ, Loken J, Steensen M, Fox Z, Tousi H, Soe-Jensen P, Lauritsen AO, Strange D, Petersen PL, Reiter N, Hestad S, Thormar K, Fjeldborg P, Larsen KM, Drenck NE, Ostergaard C, Kjaer J, Grarup J, Lundgren JD; Procalcitonin And Survival Study (PASS) Group. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med. 2011 Sep;39(9):2048-58. doi: 10.1097/CCM.0b013e31821e8791.
- Jensen JU, Lundgren B, Hein L, Mohr T, Petersen PL, Andersen LH, Lauritsen AO, Hougaard S, Mantoni T, Bomler B, Thornberg KJ, Thormar K, Loken J, Steensen M, Carl P, Petersen JA, Tousi H, Soe-Jensen P, Bestle M, Hestad S, Andersen MH, Fjeldborg P, Larsen KM, Rossau C, Thomsen CB, Ostergaard C, Kjaer J, Grarup J, Lundgren JD. 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. BMC Infect Dis. 2008 Jul 13;8:91. doi: 10.1186/1471-2334-8-91.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PASS (Other)
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