Placebo Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Severe Sepsis Septic Shock |
Drug: sodium-selenite Drug: Placebo Procedure: Procalcitonin guided therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | Prospective, Randomized Multicenter Trial of Adjunctive Intravenous Therapy With Sodium-selenite(Selenase®, Double-blinded) and a Procalcitonin Guided Causal Therapy (Open) of Severe Sepsis or Septic Shock. |
- All cause mortality [ Time Frame: 28 days ] [ Designated as safety issue: No ]
- Mean total SOFA and SOFA subscores [ Time Frame: study duration ] [ Designated as safety issue: No ]
- All cause mortality [ Time Frame: 90 days ] [ Designated as safety issue: No ]
- Frequency and duration of mechanical ventilation [ Time Frame: 90 days ] [ Designated as safety issue: No ]
- Frequency and duration of vasopressor support [ Time Frame: 90 days ] [ Designated as safety issue: No ]
- Frequency of adverse events and severe adverse events [ Time Frame: study duration ] [ Designated as safety issue: Yes ]
- Clinical cure and microbiological cure [ Time Frame: days 4, 7, 10, 14 ] [ Designated as safety issue: No ]
- Duration of antimicrobial therapy [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Costs of antimicrobial therapy [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Time to change of antibiotic therapy [ Time Frame: duration of study ] [ Designated as safety issue: No ]
- Days alive without antimicrobial therapy [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Frequency of resistancies against antibiotics (VRE, MRSA, ESBL) [ Time Frame: study duration ] [ Designated as safety issue: Yes ]
- ICU length of stay [ Time Frame: 90 days ] [ Designated as safety issue: No ]
- Hospital length of stay [ Time Frame: 90 days ] [ Designated as safety issue: No ]
- Rate of surgical procedures for focus control [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Rate of procedures to diagnose infections [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Frequency of new infections [ Time Frame: study duration ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 1180 |
| Study Start Date: | November 2009 |
| Estimated Study Completion Date: | June 2013 |
| Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: SelPCT
Patient receives sodium-selenite; causal therapy is guided by a PCT based algorithm.
|
Drug: sodium-selenite
An intravenous bolus of 1000 µg followed by a continuous intravenous infusion of 1000 µg/day until patient is discharged from the ICU but not more than 21 applications à 24 hours.
Other Name: selenase T
Procedure: Procalcitonin guided therapy
Causal therapy of sepsis is guided by applying the following algorithm: Day 4: PCT drop from baseline >=50%: no change in causal therapy; PCT drop from baseline <50%: change or optimize antimicrobial therapy, new intervention (i.e. surgery, diagnostics) recommended for source control. Day 7, 10, 14: PCT <=1.0 ng/ml: finish antimicrobial therapy; PCT >1.0 ng/ml and PCT drop from last PCT measurement >=50%: finish antimicrobial therapy; PCT >1.0 ng/ml and PCT drop from last PCT measurement <50%: change or optimize antimicrobial therapy, new intervention (i.e. surgery, diagnostics) recommended for source control. |
|
Active Comparator: SelKon
Patient receives sodium-selenite; causal therapy is not guided by a PCT based algorithm.
|
Drug: sodium-selenite
An intravenous bolus of 1000 µg followed by a continuous intravenous infusion of 1000 µg/day until patient is discharged from the ICU but not more than 21 applications à 24 hours.
Other Name: selenase T
|
|
Placebo Comparator: PlacPCT
Patient receives placebo; causal therapy is guided by a PCT based algorithm.
|
Drug: Placebo
An intravenous bolus of placebo followed by a continuous intravenous infusion with placebo until patient is discharged from the ICU but not more than 21 applications à 24 hours.
Other Name: 0.9 % sodium chlorid
Procedure: Procalcitonin guided therapy
Causal therapy of sepsis is guided by applying the following algorithm: Day 4: PCT drop from baseline >=50%: no change in causal therapy; PCT drop from baseline <50%: change or optimize antimicrobial therapy, new intervention (i.e. surgery, diagnostics) recommended for source control. Day 7, 10, 14: PCT <=1.0 ng/ml: finish antimicrobial therapy; PCT >1.0 ng/ml and PCT drop from last PCT measurement >=50%: finish antimicrobial therapy; PCT >1.0 ng/ml and PCT drop from last PCT measurement <50%: change or optimize antimicrobial therapy, new intervention (i.e. surgery, diagnostics) recommended for source control. |
|
Placebo Comparator: PlacKon
Patient receives placebo; causal therapy is not guided by a PCT based algorithm.
|
Drug: Placebo
An intravenous bolus of placebo followed by a continuous intravenous infusion with placebo until patient is discharged from the ICU but not more than 21 applications à 24 hours.
Other Name: 0.9 % sodium chlorid
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Severe sepsis or septic shock according to ACCP/SCCM criteria
- Onset of severe sepsis or septic shock <24 h
- Age >= 18 years
- Informed consent
Exclusion Criteria:
- 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
Contacts and Locations| Germany | |
| University Hospital Aachen - Dep. of Intensive Care Medicine | |
| Aachen, Germany, 52074 | |
| Klinikum Augsburg - Dep. of Medicine I | |
| Augsburg, Germany, 86156 | |
| Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine | |
| Augsburg, Germany, 86156 | |
| Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy | |
| Berlin, Germany, 12313 | |
| DRK-Kliniken Berlin-Köpenick - Dep. of Anesthesiology, Pain Therapy, and Intensive Care Medicine | |
| Berlin, Germany, 12559 | |
| Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology | |
| Berlin, Germany, 13353 | |
| Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine | |
| Berlin, Germany, 10117 | |
| Military Hospital Berlin - Dep. of Anaesthesiology and Intensive Care Medicine | |
| Berlin, Germany, 10115 | |
| Ev. Krankenhaus Gilead - Dep. of Anesthesiology | |
| Bielefeld, Germany, 33617 | |
| University Hospital Bonn - Dep. of Anesthesiology and Intensive Care Medicine | |
| Bonn, Germany, 53105 | |
| Krankenhaus Dresden-Friedrichstadt | |
| Dresden, Germany, 01067 | |
| University Hospital Dresden - Dep. of Anesthesiology and Intensive Care Med. | |
| Dresden, Germany, 01307 | |
| HELIOS Klinikum Erfurt - Dep. of Anesthesiology and Intensive Care Medicine | |
| Erfurt, Germany, 99089 | |
| University Erlangen-Nürnberg - Dep. of Medicine IV | |
| Erlangen, Germany, 91054 | |
| J.-W. Goethe University Hospital - Dep. of Anaesthesiology, Intensive Care Medicine and Pain Therapy | |
| Frankfurt/Main, Germany, 60590 | |
| University Hospital Freiburg- Dep. of Surgery | |
| Freiburg, Germany, 79106 | |
| Ernst-Moritz-Arndt-Universität Greifswald - Dep. of Anesthesiology and Intensive Care Medicine | |
| Greifswald, Germany, 17475 | |
| Georg August Universität Göttingen - Dep. of Anesthesiology and Intensive Care Medicine | |
| Göttingen, Germany, 37075 | |
| University Hospital Halle - Dep. of Medicine III | |
| Halle, Germany, 06120 | |
| Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology | |
| Halle, Germany, 06097 | |
| Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine | |
| Hamburg, Germany, 20246 | |
| Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine | |
| Heide, Germany, 25746 | |
| University Hospital Heidelberg - study center Anesthesiology/Surgery | |
| Heidelberg, Germany, 69120 | |
| University Hospital Jena, Dep. of Anesthesiology and Intensive Care Medicine | |
| Jena, Germany, 07747 | |
| University Hospital Kiel - Dep. of. Anesthesiology and Intensive Care Medicine | |
| Kiel, Germany, 24105 | |
| University Hospital Köln - Dep. of Medicine I | |
| Köln, Germany, 50924 | |
| St. Elisabeth-Krankenhaus - Dep. of Anesthesiology | |
| Köln-Hohenlind, Germany, 50935 | |
| University Hospital Leipzig - Dep. of Anesthesiology and Intensive Care Medicine | |
| Leipzig, Germany, 04103 | |
| University Hospital Mannheim - Dep. of Medicine I | |
| Mannheim, Germany, 68167 | |
| Hospital Munich Harlaching - Dep. of Internal Acute Medicine and Prevention | |
| Munich, Germany, 81545 | |
| University Hospital Munich - Dep. of Internal Medicine | |
| Munich, Germany, 80336 | |
| University Hospital Munich - Dep. of Anaesthesiology | |
| Munich, Germany, 81377 | |
| Krankenhaus München-Neuperlach - Dep. of Anesthesiology | |
| München, Germany, 81737 | |
| University Hospital Münster - Dep. of Anesthesiology and Intensive Care Medicine | |
| Münster, Germany, 48149 | |
| Klinikum Oldenburg GmbH - Dep. of Anesthesiology | |
| Oldenburg, Germany, 26133 | |
| Study Chair: | Konrad Reinhart, M.D. | University Hospital Jena; Dep. of Anesthesiology and Intensive Care Medicine |
| Study Director: | Markus Löffler | University Leipzig; Koordinierungszentrum für Klinische Studien Leipzig (KKSL) |
| Study Director: | Thomas Deufel, M. D. | University Hopitel Jena, Institute for Medical Chemistry |
More Information
Additional Information:
Publications:
| Responsible Party: | Kompetenznetz Sepsis |
| ClinicalTrials.gov Identifier: | NCT00832039 History of Changes |
| Other Study ID Numbers: | EudraCT 2007-004333-42, 01 KI 01 06, SE120301S |
| Study First Received: | January 28, 2009 |
| Last Updated: | March 26, 2013 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Kompetenznetz Sepsis:
|
sepsis adjunctive therapy sodium-selenite procalcitonin |
Additional relevant MeSH terms:
|
Sepsis Toxemia Shock Shock, Septic Infection Systemic Inflammatory Response Syndrome |
Inflammation Pathologic Processes Anti-Infective Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013