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

NCT ID: NCT00832039

Last Updated: 2016-08-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1089 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-11-30

Study Completion Date

2013-06-30

Brief Summary

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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

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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.

Conditions

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Severe Sepsis Septic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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SelPCT

Patient receives sodium-selenite; causal therapy is guided by a PCT based algorithm.

Group Type ACTIVE_COMPARATOR

sodium-selenite

Intervention Type DRUG

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.

Procalcitonin guided therapy

Intervention Type PROCEDURE

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.

SelKon

Patient receives sodium-selenite; causal therapy is not guided by a PCT based algorithm.

Group Type ACTIVE_COMPARATOR

sodium-selenite

Intervention Type DRUG

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.

PlacPCT

Patient receives placebo; causal therapy is guided by a PCT based algorithm.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Procalcitonin guided therapy

Intervention Type PROCEDURE

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.

PlacKon

Patient receives placebo; causal therapy is not guided by a PCT based algorithm.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type PROCEDURE

Other Intervention Names

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selenase T 0.9 % sodium chlorid

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biosyn

INDUSTRY

Sponsor Role collaborator

Brahms AG

INDUSTRY

Sponsor Role collaborator

Kompetenznetz Sepsis

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Konrad Reinhart, M.D.

Role: STUDY_CHAIR

University Hospital Jena; Dep. of Anesthesiology and Intensive Care Medicine

Markus Löffler

Role: STUDY_DIRECTOR

University Leipzig; Koordinierungszentrum für Klinische Studien Leipzig (KKSL)

Thomas Deufel, M. D.

Role: STUDY_DIRECTOR

University Hopitel Jena, Institute for Medical Chemistry

Locations

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University Hospital Aachen - Dep. of Intensive Care Medicine

Aachen, , Germany

Site Status

Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine

Augsburg, , Germany

Site Status

Klinikum Augsburg - Dep. of Medicine I

Augsburg, , Germany

Site Status

Military Hospital Berlin - Dep. of Anaesthesiology and Intensive Care Medicine

Berlin, , Germany

Site Status

Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine

Berlin, , Germany

Site Status

Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy

Berlin, , Germany

Site Status

DRK-Kliniken Berlin-Köpenick - Dep. of Anesthesiology, Pain Therapy, and Intensive Care Medicine

Berlin, , Germany

Site Status

Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology

Berlin, , Germany

Site Status

Ev. Krankenhaus Gilead - Dep. of Anesthesiology

Bielefeld, , Germany

Site Status

University Hospital Bonn - Dep. of Anesthesiology and Intensive Care Medicine

Bonn, , Germany

Site Status

University Hospital Köln - Dep. of Medicine I

Cologne, , Germany

Site Status

Krankenhaus Dresden-Friedrichstadt

Dresden, , Germany

Site Status

University Hospital Dresden - Dep. of Anesthesiology and Intensive Care Med.

Dresden, , Germany

Site Status

HELIOS Klinikum Erfurt - Dep. of Anesthesiology and Intensive Care Medicine

Erfurt, , Germany

Site Status

University Erlangen-Nürnberg - Dep. of Medicine IV

Erlangen, , Germany

Site Status

J.-W. Goethe University Hospital - Dep. of Anaesthesiology, Intensive Care Medicine and Pain Therapy

Frankfurt am Main, , Germany

Site Status

University Hospital Freiburg- Dep. of Surgery

Freiburg im Breisgau, , Germany

Site Status

Georg August Universität Göttingen - Dep. of Anesthesiology and Intensive Care Medicine

Göttingen, , Germany

Site Status

Ernst-Moritz-Arndt-Universität Greifswald - Dep. of Anesthesiology and Intensive Care Medicine

Greifswald, , Germany

Site Status

Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology

Halle, , Germany

Site Status

University Hospital Halle - Dep. of Medicine III

Halle, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine

Hamburg, , Germany

Site Status

Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine

Heide, , Germany

Site Status

University Hospital Heidelberg - study center Anesthesiology/Surgery

Heidelberg, , Germany

Site Status

University Hospital Jena, Dep. of Anesthesiology and Intensive Care Medicine

Jena, , Germany

Site Status

University Hospital Kiel - Dep. of. Anesthesiology and Intensive Care Medicine

Kiel, , Germany

Site Status

St. Elisabeth-Krankenhaus - Dep. of Anesthesiology

Köln-Hohenlind, , Germany

Site Status

University Hospital Leipzig - Dep. of Anesthesiology and Intensive Care Medicine

Leipzig, , Germany

Site Status

University Hospital Mannheim - Dep. of Medicine I

Mannheim, , Germany

Site Status

University Hospital Munich - Dep. of Internal Medicine

Munich, , Germany

Site Status

University Hospital Munich - Dep. of Anaesthesiology

Munich, , Germany

Site Status

Hospital Munich Harlaching - Dep. of Internal Acute Medicine and Prevention

Munich, , Germany

Site Status

Krankenhaus München-Neuperlach - Dep. of Anesthesiology

München, , Germany

Site Status

University Hospital Münster - Dep. of Anesthesiology and Intensive Care Medicine

Münster, , Germany

Site Status

Klinikum Oldenburg GmbH - Dep. of Anesthesiology

Oldenburg, , Germany

Site Status

Countries

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Germany

References

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Bloos F, Trips E, Nierhaus A, Briegel J, Heyland DK, Jaschinski U, Moerer O, Weyland A, Marx G, Grundling M, Kluge S, Kaufmann I, Ott K, Quintel M, Jelschen F, Meybohm P, Rademacher S, Meier-Hellmann A, Utzolino S, Kaisers UX, Putensen C, Elke G, Ragaller M, Gerlach H, Ludewig K, Kiehntopf M, Bogatsch H, Engel C, Brunkhorst FM, Loeffler M, Reinhart K; for SepNet Critical Care Trials Group. Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial. JAMA Intern Med. 2016 Sep 1;176(9):1266-76. doi: 10.1001/jamainternmed.2016.2514.

Reference Type RESULT
PMID: 27428731 (View on PubMed)

Guo A, Srinath J, Feuerecker M, Crucian B, Briegel J, Boulesteix AL, Kaufmann I, Chouker A. Immune function testing in sepsis patients receiving sodium selenite. J Crit Care. 2019 Aug;52:208-212. doi: 10.1016/j.jcrc.2019.05.001. Epub 2019 May 4.

Reference Type DERIVED
PMID: 31102938 (View on PubMed)

Feuerecker M, Sudhoff L, Crucian B, Pagel JI, Sams C, Strewe C, Guo A, Schelling G, Briegel J, Kaufmann I, Chouker A. Early immune anergy towards recall antigens and mitogens in patients at onset of septic shock. Sci Rep. 2018 Jan 29;8(1):1754. doi: 10.1038/s41598-018-19976-w.

Reference Type DERIVED
PMID: 29379043 (View on PubMed)

Related Links

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Other Identifiers

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01 KI 01 06

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SE120301S

Identifier Type: OTHER

Identifier Source: secondary_id

EudraCT 2007-004333-42

Identifier Type: -

Identifier Source: org_study_id

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