Placebo Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis
- Conditions
- Severe SepsisSeptic Shock
- Interventions
- Drug: sodium-seleniteDrug: PlaceboProcedure: Procalcitonin guided therapy
- Registration Number
- NCT00832039
- Lead Sponsor
- Kompetenznetz Sepsis
- Brief Summary
Severe sepsis and septic shock are diseases of infectious origin with a high risk of death. The purpose of this study is to determine whether the intravenous application of selenium (given as sodium-selenite) can reduce mortality in patients with severe sepsis or septic shock. Additionally, it is investigated, whether the measurement of procalcitonin - a marker of infection - can be used to guide anti-infectious measures in this disease.
- Detailed Description
This is a multicenter trial of the German Network Sepsis (SepNet) on patients with severe sepsis or septic shock. This study is supported by unrestricted grants.
The release of reactive oxygen species is an important factor in the development of sepsis induced multiorgan dysfunction syndrome. Common protection mechanisms are impaired in this syndrome. Serum levels of selenium, a cofactor of the glutathionperoxidase, are reduced. Several studies suggest a benefit of selenium application in patients with severe sepsis but data from large clinical trials are not available. After inclusion into the study, patients are randomly allocated to a placebo or selenium group. Treating physicians and patients are blinded regarding the allocation. The selenium group receives sodium selenite intravenously - 1000 µg as a bolus followed by a continuous infusion of 1000 µg per day until the end of ICU treatment but not longer than 21 days.
Procalcitonin (PCT) is a biomarker which is elevated in the blood of patients with severe sepsis/septic shock. Data from patients with community acquired pneumonia demonstrated that this biomarker can be used to decide on the duration of antimicrobial therapy. Studies with small sample size seem to confirm this in ICU patients with severe sepsis. However, this needs to be confirmed in a larger cohort. All patients are randomly allocated to a PCT guided algorithm or a control group. In the PCT-guided group, PCT is measured at randomization, day 4, 7, 10, and 14. Depending on the PCT course, the protocol recommends to change, alter, or stop anti-infectious measures. In the control group, anti-infectious therapy is left to the discretion of the treating physician.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1089
- Severe sepsis or septic shock according to ACCP/SCCM criteria
- Onset of severe sepsis or septic shock <24 h
- Age >= 18 years
- Informed consent
- Pregnant or breast-feeding women
- Fertile female women without effective contraception
- Participation in interventional clinical trial within the last 30 days
- Current participation in any study
- Former participation in this trial
- Selenium intoxication
- No commitment to full patient support (i.e. DNR order)
- Patient's death is considered imminent due to coexisting disease
- Relationship of the patient to study team member (i.e. colleague, relative)
- Infection where guidelines recommend a longer duration of antimicrobial therapy (i.e. endocarditis, tuberculosis, malaria etc)
- Immunocompromised patients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description SelPCT sodium-selenite Patient receives sodium-selenite; causal therapy is guided by a PCT based algorithm. SelPCT Procalcitonin guided therapy Patient receives sodium-selenite; causal therapy is guided by a PCT based algorithm. SelKon sodium-selenite Patient receives sodium-selenite; causal therapy is not guided by a PCT based algorithm. PlacPCT Placebo Patient receives placebo; causal therapy is guided by a PCT based algorithm. PlacPCT Procalcitonin guided therapy Patient receives placebo; causal therapy is guided by a PCT based algorithm. PlacKon Placebo Patient receives placebo; causal therapy is not guided by a PCT based algorithm.
- Primary Outcome Measures
Name Time Method All cause mortality 28 days
- Secondary Outcome Measures
Name Time Method Hospital length of stay 90 days Mean total SOFA and SOFA subscores study duration All cause mortality 90 days Frequency and duration of mechanical ventilation 90 days Frequency and duration of vasopressor support 90 days Frequency of adverse events and severe adverse events study duration Duration of antimicrobial therapy study duration Clinical cure and microbiological cure days 4, 7, 10, 14 Costs of antimicrobial therapy study duration Time to change of antibiotic therapy duration of study Days alive without antimicrobial therapy study duration Frequency of resistancies against antibiotics (VRE, MRSA, ESBL) study duration ICU length of stay 90 days Rate of surgical procedures for focus control study duration Rate of procedures to diagnose infections study duration Frequency of new infections study duration
Trial Locations
- Locations (35)
Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy
🇩🇪Berlin, Germany
Klinikum Augsburg - Dep. of Medicine I
🇩🇪Augsburg, Germany
University Erlangen-Nürnberg - Dep. of Medicine IV
🇩🇪Erlangen, Germany
University Hospital Leipzig - Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Leipzig, Germany
University Hospital Munich - Dep. of Internal Medicine
🇩🇪Munich, Germany
Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine
🇩🇪Hamburg, Germany
Ev. Krankenhaus Gilead - Dep. of Anesthesiology
🇩🇪Bielefeld, Germany
University Hospital Köln - Dep. of Medicine I
🇩🇪Köln, Germany
Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Augsburg, Germany
University Hospital Aachen - Dep. of Intensive Care Medicine
🇩🇪Aachen, Germany
Military Hospital Berlin - Dep. of Anaesthesiology and Intensive Care Medicine
🇩🇪Berlin, Germany
Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Berlin, Germany
DRK-Kliniken Berlin-Köpenick - Dep. of Anesthesiology, Pain Therapy, and Intensive Care Medicine
🇩🇪Berlin, Germany
Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology
🇩🇪Berlin, Germany
University Hospital Bonn - Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Bonn, Germany
University Hospital Dresden - Dep. of Anesthesiology and Intensive Care Med.
🇩🇪Dresden, Germany
J.-W. Goethe University Hospital - Dep. of Anaesthesiology, Intensive Care Medicine and Pain Therapy
🇩🇪Frankfurt/Main, Germany
University Hospital Freiburg- Dep. of Surgery
🇩🇪Freiburg, Germany
Ernst-Moritz-Arndt-Universität Greifswald - Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Greifswald, Germany
Georg August Universität Göttingen - Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Göttingen, Germany
Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Heide, Germany
University Hospital Heidelberg - study center Anesthesiology/Surgery
🇩🇪Heidelberg, Germany
Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology
🇩🇪Halle, Germany
University Hospital Mannheim - Dep. of Medicine I
🇩🇪Mannheim, Germany
University Hospital Kiel - Dep. of. Anesthesiology and Intensive Care Medicine
🇩🇪Kiel, Germany
University Hospital Jena, Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Jena, Germany
St. Elisabeth-Krankenhaus - Dep. of Anesthesiology
🇩🇪Köln-Hohenlind, Germany
Hospital Munich Harlaching - Dep. of Internal Acute Medicine and Prevention
🇩🇪Munich, Germany
University Hospital Munich - Dep. of Anaesthesiology
🇩🇪Munich, Germany
Klinikum Oldenburg GmbH - Dep. of Anesthesiology
🇩🇪Oldenburg, Germany
Krankenhaus München-Neuperlach - Dep. of Anesthesiology
🇩🇪München, Germany
University Hospital Münster - Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Münster, Germany
University Hospital Halle - Dep. of Medicine III
🇩🇪Halle, Germany
HELIOS Klinikum Erfurt - Dep. of Anesthesiology and Intensive Care Medicine
🇩🇪Erfurt, Germany
Krankenhaus Dresden-Friedrichstadt
🇩🇪Dresden, Germany