The Procalcitonin and Survival Study

Study Overview
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Brief Summary
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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).

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ill patients increases gravely when Procalcitonin levels increase from day to day (own submitted, though yet unpublished data).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

Official Title
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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

Conditions
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Localized Infection, Sepsis, Multiple Organ Failure

Intervention / Treatment
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* Procedure: Earlier therapeutic changes regarding infection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PCT guided<br>Procalcitonin guided treatment of infections in the ICU. Intervention: Intensification of antibiotics, surgery, microbiologic testing and diagnostic imaging, when Procalcitonin levels are increasing | Procedure: Earlier therapeutic changes regarding infection<br>* For every day Procalcitonin levels increase in the intervention group, antibiotics, surgery, diagnostic imaging and microbiologic testing is intensified<br>|
| Sham Comparator: Control<br>These patients receive Standard of Care which is the recommended treatment in the given ICU | Procedure: Earlier therapeutic changes regarding infection<br>* For every day Procalcitonin levels increase in the intervention group, antibiotics, surgery, diagnostic imaging and microbiologic testing is intensified<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality/survival |  | 28 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality/survival |  | 60 day | 
| mortality/survival |  | 90 day | 
| mortality/survival |  | 120 day | 
| mortality/survival |  | 180 day | 
| Consumption of antimicrobial chemotherapy |  | 28 day | 
| Prevalence of complications to infection: sepsis |  | 28 day | 
| severe sepsis |  | 28 day | 
| septic shock |  | 28 day | 
| Multi Organ Dysfunction Syndrome |  | 28 day | 
| Disseminated Intravascular Coagulation |  | 28 day | 
| use of diagnostic imaging during admission to the ICU |  | 28 day | 
| Quality of life post-ICU |  | 180 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Procalcitonin, Sepsis, Intensive Care Unit, Sepsis and Complications, Organ Failure