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Placebo Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT)

This study has been completed.
Sponsor:
Collaborators:
Biosyn
Brahms AG
Information provided by (Responsible Party):
Kompetenznetz Sepsis
ClinicalTrials.gov Identifier:
NCT00832039
First received: January 28, 2009
Last updated: June 28, 2013
Last verified: June 2013
  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.

Resource links provided by NLM:


Further study details as provided by Kompetenznetz Sepsis:

Primary Outcome Measures:
  • All cause mortality [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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
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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00832039

Locations
Germany
University Hospital Aachen - Dep. of Intensive Care Medicine
Aachen, Germany, 52074
Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine
Augsburg, Germany, 86156
Klinikum Augsburg - Dep. of Medicine I
Augsburg, Germany, 86156
Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology
Berlin, Germany, 13353
Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine
Berlin, Germany, 10117
DRK-Kliniken Berlin-Köpenick - Dep. of Anesthesiology, Pain Therapy, and Intensive Care Medicine
Berlin, Germany, 12559
Military Hospital Berlin - Dep. of Anaesthesiology and Intensive Care Medicine
Berlin, Germany, 10115
Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy
Berlin, Germany, 12313
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
Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology
Halle, Germany, 06097
University Hospital Halle - Dep. of Medicine III
Halle, Germany, 06120
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 Anaesthesiology
Munich, Germany, 81377
University Hospital Munich - Dep. of Internal Medicine
Munich, Germany, 80336
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
Sponsors and Collaborators
Kompetenznetz Sepsis
Biosyn
Brahms AG
Investigators
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: June 28, 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
Shock, Septic
Toxemia
Infection
Inflammation
Pathologic Processes
Shock
Systemic Inflammatory Response Syndrome
Anti-Infective Agents
Selenious Acid
Sodium Selenite
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Trace Elements

ClinicalTrials.gov processed this record on November 24, 2014