Clinical trial NCT00832039: Placebo Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Sepsis
Septic Shock
Keywords: sepsis
adjunctive therapy
sodium-selenite
procalcitonin
Lead sponsor: Kompetenznetz Sepsis
Sponsor class: NETWORK
Collaborators: name: Biosyn
name: Brahms AG
First posted: 2009-01-29
Enrollment: 1089
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: All cause mortality
timeFrame: 28 days
Secondary outcomes:
measure: Mean total SOFA and SOFA subscores
timeFrame: study duration
measure: All cause mortality
timeFrame: 90 days
measure: Frequency and duration of mechanical ventilation
timeFrame: 90 days
measure: Frequency and duration of vasopressor support
timeFrame: 90 days
measure: Frequency of adverse events and severe adverse events
timeFrame: study duration
measure: Clinical cure and microbiological cure
timeFrame: days 4, 7, 10, 14
measure: Duration of antimicrobial therapy
timeFrame: study duration
measure: Costs of antimicrobial therapy
timeFrame: study duration
measure: Time to change of antibiotic therapy
timeFrame: duration of study
measure: Days alive without antimicrobial therapy
timeFrame: study duration
measure: Frequency of resistancies against antibiotics (VRE, MRSA, ESBL)
timeFrame: study duration
measure: ICU length of stay
timeFrame: 90 days
measure: Hospital length of stay
timeFrame: 90 days
measure: Rate of surgical procedures for focus control
timeFrame: study duration
measure: Rate of procedures to diagnose infections
timeFrame: study duration
measure: Frequency of new infections
timeFrame: study duration
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: University Hospital Aachen - Dep. of Intensive Care Medicine
city: Augsburg
country: Germany
facility: Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine
city: Augsburg
country: Germany
facility: Klinikum Augsburg - Dep. of Medicine I
city: Berlin
country: Germany
facility: Military Hospital Berlin - Dep. of Anaesthesiology and Intensive Care Medicine
city: Berlin
country: Germany
facility: Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy
city: Berlin
country: Germany
facility: DRK-Kliniken Berlin-Köpenick - Dep. of Anesthesiology, Pain Therapy, and Intensive Care Medicine
city: Berlin
country: Germany
facility: Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology
city: Bielefeld
country: Germany
facility: Ev. Krankenhaus Gilead - Dep. of Anesthesiology
city: Bonn
country: Germany
facility: University Hospital Bonn - Dep. of Anesthesiology and Intensive Care Medicine
city: Dresden
country: Germany
facility: Krankenhaus Dresden-Friedrichstadt
city: Dresden
country: Germany
facility: University Hospital Dresden - Dep. of Anesthesiology and Intensive Care Med.
city: Erfurt
country: Germany
facility: HELIOS Klinikum Erfurt - Dep. of Anesthesiology and Intensive Care Medicine
city: Erlangen
country: Germany
facility: University Erlangen-Nürnberg - Dep. of Medicine IV
city: Frankfurt/Main
country: Germany
facility: J.-W. Goethe University Hospital - Dep. of Anaesthesiology, Intensive Care Medicine and Pain Therapy
city: Freiburg
country: Germany
facility: University Hospital Freiburg- Dep. of Surgery
city: Greifswald
country: Germany
facility: Ernst-Moritz-Arndt-Universität Greifswald - Dep. of Anesthesiology and Intensive Care Medicine
city: Göttingen
country: Germany
facility: Georg August Universität Göttingen - Dep. of Anesthesiology and Intensive Care Medicine
city: Halle
country: Germany
facility: Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology
city: Halle
country: Germany
facility: University Hospital Halle - Dep. of Medicine III
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg - study center Anesthesiology/Surgery
city: Heide
country: Germany
facility: Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine
city: Jena
country: Germany
facility: University Hospital Jena, Dep. of Anesthesiology and Intensive Care Medicine
city: Kiel
country: Germany
facility: University Hospital Kiel - Dep. of. Anesthesiology and Intensive Care Medicine
city: Köln-Hohenlind
country: Germany
facility: St. Elisabeth-Krankenhaus - Dep. of Anesthesiology
city: Köln
country: Germany
facility: University Hospital Köln - Dep. of Medicine I
city: Leipzig
country: Germany
facility: University Hospital Leipzig - Dep. of Anesthesiology and Intensive Care Medicine
city: Mannheim
country: Germany
facility: University Hospital Mannheim - Dep. of Medicine I
city: Munich
country: Germany
facility: University Hospital Munich - Dep. of Internal Medicine
city: Munich
country: Germany
facility: University Hospital Munich - Dep. of Anaesthesiology
city: Munich
country: Germany
facility: Hospital Munich Harlaching - Dep. of Internal Acute Medicine and Prevention
city: München
country: Germany
facility: Krankenhaus München-Neuperlach - Dep. of Anesthesiology
city: Münster
country: Germany
facility: University Hospital Münster - Dep. of Anesthesiology and Intensive Care Medicine
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg GmbH - Dep. of Anesthesiology
Study officials:
affiliation: University Hospital Jena; Dep. of Anesthesiology and Intensive Care Medicine
name: Konrad Reinhart, M.D.
role: STUDY_CHAIR
affiliation: University Leipzig; Koordinierungszentrum für Klinische Studien Leipzig (KKSL)
name: Markus Löffler
role: STUDY_DIRECTOR
affiliation: University Hopitel Jena, Institute for Medical Chemistry
name: Thomas Deufel, M. D.
role: STUDY_DIRECTOR
References:
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.
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.
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.