The Procalcitonin and Survival Study (PASS)

March 3, 2010 updated by: Danish Procalcitonin Study Group

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

This is a randomised, single blinded, multicentre trial to evaluate whether daily procalcitonin (PCT) measurements and immediate diagnostic and therapeutic responses to abnormal values and day-to-day changes can reduce the mortality of critically ill patients in the Intensive Care Unit (ICU).

Study Overview

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critically ill patients increases gravely when Procalcitonin levels increase from day to day (own submitted, though yet unpublished data).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

Interventional

Enrollment (Actual)

1200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Copenhagen
      • Copenhagen NV, Copenhagen, Denmark, DK-2400
        • Intensive Care Unit, Bispebjerg Hospital
      • Gentofte, Copenhagen, Denmark, DK-2820
        • Intensive Care Unit, KAS Gentofte
      • Glostrup, Copenhagen, Denmark, DK-2600
        • Intensive Care Unit, KAS Glostrup, Copenhagen University Hospital
      • Herlev, Copenhagen, Denmark, DK-2730
        • Intensive Care Unit, Herlev Hospital
      • Hvidovre, Copenhagen, Denmark, DK-2650
        • Intensive Care Unit 542, Hvidovre Hospital, Copenhagen University Hospital
    • Frederiksborg County
      • Hilleroed, Frederiksborg County, Denmark, DK-3400
        • Intensive Care Unit, Hilleroed Sygehus
    • Midtjylland
      • Skejby, Århus, Midtjylland, Denmark, DK-8200
        • Skejby Sygehus
      • Århus, Midtjylland, Denmark, DK-8000
        • Intensive Care Unit, Århus Sygehus, Nørrebrogade
    • Sjælland
      • Roskilde, Sjælland, Denmark, DK-4000
        • Roskilde Sygehus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Fulfilment of all of the following three criteria:

  1. Male or female, aged > 18 years of age.
  2. 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
  3. 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:

  1. 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.
  2. 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.
  3. 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
For every day Procalcitonin levels increase in the intervention group, antibiotics, surgery, diagnostic imaging and microbiologic testing is intensified
Sham Comparator: Control
These patients receive "Standard of Care" which is the recommended treatment in the given ICU
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
severe sepsis
Time Frame: 28 day
28 day
septic shock
Time Frame: 28 day
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

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

September 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

January 1, 2006

First Submitted That Met QC Criteria

January 1, 2006

First Posted (Estimate)

January 4, 2006

Study Record Updates

Last Update Posted (Estimate)

March 4, 2010

Last Update Submitted That Met QC Criteria

March 3, 2010

Last Verified

March 1, 2010

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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