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

Primary Purpose

Severe Sepsis, Septic Shock

Status

Completed

Phase

Phase 3

Locations

Germany

Study Type

Interventional

Intervention

sodium-selenite

Placebo

Procalcitonin guided therapy

About this trial

This is an interventional treatment trial for Severe Sepsis focused on measuring sepsis, adjunctive therapy, sodium-selenite, procalcitonin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospital Aachen - Dep. of Intensive Care Medicine
Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine
Klinikum Augsburg - Dep. of Medicine I
Military Hospital Berlin - Dep. of Anaesthesiology and Intensive Care Medicine
Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine
Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy
DRK-Kliniken Berlin-Köpenick - Dep. of Anesthesiology, Pain Therapy, and Intensive Care Medicine
Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology
Ev. Krankenhaus Gilead - Dep. of Anesthesiology
University Hospital Bonn - Dep. of Anesthesiology and Intensive Care Medicine
Krankenhaus Dresden-Friedrichstadt
University Hospital Dresden - Dep. of Anesthesiology and Intensive Care Med.
HELIOS Klinikum Erfurt - Dep. of Anesthesiology and Intensive Care Medicine
University Erlangen-Nürnberg - Dep. of Medicine IV
J.-W. Goethe University Hospital - Dep. of Anaesthesiology, Intensive Care Medicine and Pain Therapy
University Hospital Freiburg- Dep. of Surgery
Ernst-Moritz-Arndt-Universität Greifswald - Dep. of Anesthesiology and Intensive Care Medicine
Georg August Universität Göttingen - Dep. of Anesthesiology and Intensive Care Medicine
Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology
University Hospital Halle - Dep. of Medicine III
Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine
University Hospital Heidelberg - study center Anesthesiology/Surgery
Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine
University Hospital Jena, Dep. of Anesthesiology and Intensive Care Medicine
University Hospital Kiel - Dep. of. Anesthesiology and Intensive Care Medicine
St. Elisabeth-Krankenhaus - Dep. of Anesthesiology
University Hospital Köln - Dep. of Medicine I
University Hospital Leipzig - Dep. of Anesthesiology and Intensive Care Medicine
University Hospital Mannheim - Dep. of Medicine I
University Hospital Munich - Dep. of Internal Medicine
University Hospital Munich - Dep. of Anaesthesiology
Hospital Munich Harlaching - Dep. of Internal Acute Medicine and Prevention
Krankenhaus München-Neuperlach - Dep. of Anesthesiology
University Hospital Münster - Dep. of Anesthesiology and Intensive Care Medicine
Klinikum Oldenburg GmbH - Dep. of Anesthesiology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Arm Label

SelPCT

SelKon

PlacPCT

PlacKon

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

All cause mortality

Secondary Outcome Measures

Mean total SOFA and SOFA subscores

All cause mortality

Frequency and duration of mechanical ventilation

Frequency and duration of vasopressor support

Frequency of adverse events and severe adverse events

Clinical cure and microbiological cure

Duration of antimicrobial therapy

Costs of antimicrobial therapy

Time to change of antibiotic therapy

Days alive without antimicrobial therapy

Frequency of resistancies against antibiotics (VRE, MRSA, ESBL)

ICU length of stay

Hospital length of stay

Rate of surgical procedures for focus control

Rate of procedures to diagnose infections

Frequency of new infections

Full Information

NCT ID

NCT00832039

First Posted

January 28, 2009

Last Updated

August 11, 2016

Sponsor

Kompetenznetz Sepsis

Collaborators

Biosyn, Brahms AG

1. Study Identification

Unique Protocol Identification Number

NCT00832039

Brief Title

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

Acronym

SISPCT

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.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2016

Overall Recruitment Status

Completed

Study Start Date

November 2009 (undefined)

Primary Completion Date

March 2013 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Kompetenznetz Sepsis

Collaborators

Biosyn, Brahms AG

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe Sepsis, Septic Shock

Keywords

sepsis, adjunctive therapy, sodium-selenite, procalcitonin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Factorial Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1089 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SelPCT

Arm Type

Active Comparator

Arm Description

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

Arm Title

SelKon

Arm Type

Active Comparator

Arm Description

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

Arm Title

PlacPCT

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

PlacKon

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

sodium-selenite

Other Intervention Name(s)

selenase T

Intervention Description

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

Intervention Name(s)

Placebo

Other Intervention Name(s)

0.9 % sodium chlorid

Intervention Description

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

Procedure

Intervention Name(s)

Procalcitonin guided therapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

All cause mortality

Time Frame

28 days

Secondary Outcome Measure Information:

Title

Mean total SOFA and SOFA subscores

Time Frame

study duration

Title

All cause mortality

Time Frame

90 days

Title

Frequency and duration of mechanical ventilation

Time Frame

90 days

Title

Frequency and duration of vasopressor support

Time Frame

90 days

Title

Frequency of adverse events and severe adverse events

Time Frame

study duration

Title

Clinical cure and microbiological cure

Time Frame

days 4, 7, 10, 14

Title

Duration of antimicrobial therapy

Time Frame

study duration

Title

Costs of antimicrobial therapy

Time Frame

study duration

Title

Time to change of antibiotic therapy

Time Frame

duration of study

Title

Days alive without antimicrobial therapy

Time Frame

study duration

Title

Frequency of resistancies against antibiotics (VRE, MRSA, ESBL)

Time Frame

study duration

Title

ICU length of stay

Time Frame

90 days

Title

Hospital length of stay

Time Frame

90 days

Title

Rate of surgical procedures for focus control

Time Frame

study duration

Title

Rate of procedures to diagnose infections

Time Frame

study duration

Title

Frequency of new infections

Time Frame

study duration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Konrad Reinhart, M.D.

Organizational Affiliation

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

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Markus Löffler

Organizational Affiliation

University Leipzig; Koordinierungszentrum für Klinische Studien Leipzig (KKSL)

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Thomas Deufel, M. D.

Organizational Affiliation

University Hopitel Jena, Institute for Medical Chemistry

Official's Role

Study Director

Facility Information:

Facility Name

University Hospital Aachen - Dep. of Intensive Care Medicine

City

Aachen

ZIP/Postal Code

52074

Country

Germany

Facility Name

Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine

City

Augsburg

ZIP/Postal Code

86156

Country

Germany

Facility Name

Klinikum Augsburg - Dep. of Medicine I

City

Augsburg

ZIP/Postal Code

86156

Country

Germany

Facility Name

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

City

Berlin

ZIP/Postal Code

10115

Country

Germany

Facility Name

Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Facility Name

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

City

Berlin

ZIP/Postal Code

12313

Country

Germany

Facility Name

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

City

Berlin

ZIP/Postal Code

12559

Country

Germany

Facility Name

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

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Ev. Krankenhaus Gilead - Dep. of Anesthesiology

City

Bielefeld

ZIP/Postal Code

33617

Country

Germany

Facility Name

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

City

Bonn

ZIP/Postal Code

53105

Country

Germany

Facility Name

Krankenhaus Dresden-Friedrichstadt

City

Dresden

ZIP/Postal Code

01067

Country

Germany

Facility Name

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

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

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

City

Erfurt

ZIP/Postal Code

99089

Country

Germany

Facility Name

University Erlangen-Nürnberg - Dep. of Medicine IV

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

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

City

Frankfurt/Main

ZIP/Postal Code

60590

Country

Germany

Facility Name

University Hospital Freiburg- Dep. of Surgery

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

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

City

Greifswald

ZIP/Postal Code

17475

Country

Germany

Facility Name

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

City

Göttingen

ZIP/Postal Code

37075

Country

Germany

Facility Name

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

City

Halle

ZIP/Postal Code

06097

Country

Germany

Facility Name

University Hospital Halle - Dep. of Medicine III

City

Halle

ZIP/Postal Code

06120

Country

Germany

Facility Name

Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

University Hospital Heidelberg - study center Anesthesiology/Surgery

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine

City

Heide

ZIP/Postal Code

25746

Country

Germany

Facility Name

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

City

Jena

ZIP/Postal Code

07747

Country

Germany

Facility Name

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

City

Kiel

ZIP/Postal Code

24105

Country

Germany

Facility Name

St. Elisabeth-Krankenhaus - Dep. of Anesthesiology

City

Köln-Hohenlind

ZIP/Postal Code

50935

Country

Germany

Facility Name

University Hospital Köln - Dep. of Medicine I

City

Köln

ZIP/Postal Code

50924

Country

Germany

Facility Name

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

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

University Hospital Mannheim - Dep. of Medicine I

City

Mannheim

ZIP/Postal Code

68167

Country

Germany

Facility Name

University Hospital Munich - Dep. of Internal Medicine

City

Munich

ZIP/Postal Code

80336

Country

Germany

Facility Name

University Hospital Munich - Dep. of Anaesthesiology

City

Munich

ZIP/Postal Code

81377

Country

Germany

Facility Name

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

City

Munich

ZIP/Postal Code

81545

Country

Germany

Facility Name

Krankenhaus München-Neuperlach - Dep. of Anesthesiology

City

München

ZIP/Postal Code

81737

Country

Germany

Facility Name

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

City

Münster

ZIP/Postal Code

48149

Country

Germany

Facility Name

Klinikum Oldenburg GmbH - Dep. of Anesthesiology

City

Oldenburg

ZIP/Postal Code

26133

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

27428731

Citation

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.

Results Reference

result

PubMed Identifier

31102938

Citation

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.

Results Reference

derived

PubMed Identifier

29379043

Citation

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.

Results Reference

derived

Links:

URL

http://www.sepsis-gesellschaft.de

Description

German Sepsis Society

URL

http://www.sepsis-gesellschaft.de/DSG/Deutsch/SepNet?sid=nbGlH39rI6b9u2fBVVhxiM&iid=1

Description

Competence Network Sepsis (SepNet)

URL

http://www.survivingsepsis.org

Description

Surviving Sepsis Campaign

Learn more about this trial

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

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