The Procalcitonin and Survival Study

Sepsis Clinical Trial

— PASS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00271752
• Other study ID #: PASS
• Status: Completed
• Phase: N/A
• First received: January 1, 2006
• Last updated: March 3, 2010
• Start date: January 2006
• Est. completion date: September 2009

Study information

• Verified date: March 2010
• Source: Danish Procalcitonin Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: National Board of Health
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1200
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Localized Infection
• Multiple Organ Failure
• Sepsis

Intervention

Procedure:
• Earlier therapeutic changes regarding infection
For every day Procalcitonin levels increase in the intervention group, antibiotics, surgery, diagnostic imaging and microbiologic testing is intensified

Locations

Country	Name	City	State
Denmark	Intensive Care Unit, Århus Sygehus, Nørrebrogade	Århus	Midtjylland
Denmark	Intensive Care Unit, Bispebjerg Hospital	Copenhagen NV	Copenhagen
Denmark	Intensive Care Unit, KAS Gentofte	Gentofte	Copenhagen
Denmark	Intensive Care Unit, KAS Glostrup, Copenhagen University Hospital	Glostrup	Copenhagen
Denmark	Intensive Care Unit, Herlev Hospital	Herlev	Copenhagen
Denmark	Intensive Care Unit, Hilleroed Sygehus	Hilleroed	Frederiksborg County
Denmark	Intensive Care Unit 542, Hvidovre Hospital, Copenhagen University Hospital	Hvidovre	Copenhagen
Denmark	Roskilde Sygehus	Roskilde	Sjælland
Denmark	Skejby Sygehus	Skejby, Århus	Midtjylland

Sponsors (4)

Lead Sponsor	Collaborator
Danish Procalcitonin Study Group	Copenhagen HIV Programme, Danish Research Agency, Hvidovre University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mortality/survival		28 day	Yes
Secondary	mortality/survival		60 day	Yes
Secondary	mortality/survival		90 day	Yes
Secondary	mortality/survival		120 day	Yes
Secondary	mortality/survival		180 day	Yes
Secondary	Consumption of antimicrobial chemotherapy		28 day	No
Secondary	Prevalence of complications to infection: sepsis		28 day	Yes
Secondary	severe sepsis		28 day	Yes
Secondary	septic shock		28 day	Yes
Secondary	Multi Organ Dysfunction Syndrome		28 day	Yes
Secondary	Disseminated Intravascular Coagulation		28 day	Yes
Secondary	use of diagnostic imaging during admission to the ICU		28 day	No
Secondary	Quality of life post-ICU		180 day	No