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

Sponsor

Kompetenznetz Sepsis (Other)

Overall Status

Completed

CT.gov ID

NCT00832039

Collaborator

Biosyn (Industry), Brahms AG (Industry)

1,089

Enrollment

Locations

Arms

Duration (Months)

31.1

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Sepsis Septic Shock	Drug: sodium-selenite Drug: Placebo Procedure: Procalcitonin guided therapy	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1089 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double (Participant, 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.

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: 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 Names: 0.9 % sodium chlorid

Outcome Measures

Primary Outcome Measures

All cause mortality [28 days]

Secondary Outcome Measures

Mean total SOFA and SOFA subscores [study duration]
All cause mortality [90 days]
Frequency and duration of mechanical ventilation [90 days]
Frequency and duration of vasopressor support [90 days]
Frequency of adverse events and severe adverse events [study duration]
Clinical cure and microbiological cure [days 4, 7, 10, 14]
Duration of antimicrobial therapy [study duration]
Costs of antimicrobial therapy [study duration]
Time to change of antibiotic therapy [duration of study]
Days alive without antimicrobial therapy [study duration]
Frequency of resistancies against antibiotics (VRE, MRSA, ESBL) [study duration]
ICU length of stay [90 days]
Hospital length of stay [90 days]
Rate of surgical procedures for focus control [study duration]
Rate of procedures to diagnose infections [study duration]
Frequency of new infections [study duration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Hospital Aachen - Dep. of Intensive Care Medicine	Aachen	Germany	52074
2	Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine	Augsburg	Germany	86156
3	Klinikum Augsburg - Dep. of Medicine I	Augsburg	Germany	86156
4	Military Hospital Berlin - Dep. of Anaesthesiology and Intensive Care Medicine	Berlin	Germany	10115
5	Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine	Berlin	Germany	10117
6	Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy	Berlin	Germany	12313
7	DRK-Kliniken Berlin-Köpenick - Dep. of Anesthesiology, Pain Therapy, and Intensive Care Medicine	Berlin	Germany	12559
8	Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology	Berlin	Germany	13353
9	Ev. Krankenhaus Gilead - Dep. of Anesthesiology	Bielefeld	Germany	33617
10	University Hospital Bonn - Dep. of Anesthesiology and Intensive Care Medicine	Bonn	Germany	53105
11	Krankenhaus Dresden-Friedrichstadt	Dresden	Germany	01067
12	University Hospital Dresden - Dep. of Anesthesiology and Intensive Care Med.	Dresden	Germany	01307
13	HELIOS Klinikum Erfurt - Dep. of Anesthesiology and Intensive Care Medicine	Erfurt	Germany	99089
14	University Erlangen-Nürnberg - Dep. of Medicine IV	Erlangen	Germany	91054
15	J.-W. Goethe University Hospital - Dep. of Anaesthesiology, Intensive Care Medicine and Pain Therapy	Frankfurt/Main	Germany	60590
16	University Hospital Freiburg- Dep. of Surgery	Freiburg	Germany	79106
17	Ernst-Moritz-Arndt-Universität Greifswald - Dep. of Anesthesiology and Intensive Care Medicine	Greifswald	Germany	17475
18	Georg August Universität Göttingen - Dep. of Anesthesiology and Intensive Care Medicine	Göttingen	Germany	37075
19	Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology	Halle	Germany	06097
20	University Hospital Halle - Dep. of Medicine III	Halle	Germany	06120
21	Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine	Hamburg	Germany	20246
22	University Hospital Heidelberg - study center Anesthesiology/Surgery	Heidelberg	Germany	69120
23	Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine	Heide	Germany	25746
24	University Hospital Jena, Dep. of Anesthesiology and Intensive Care Medicine	Jena	Germany	07747
25	University Hospital Kiel - Dep. of. Anesthesiology and Intensive Care Medicine	Kiel	Germany	24105
26	St. Elisabeth-Krankenhaus - Dep. of Anesthesiology	Köln-Hohenlind	Germany	50935
27	University Hospital Köln - Dep. of Medicine I	Köln	Germany	50924
28	University Hospital Leipzig - Dep. of Anesthesiology and Intensive Care Medicine	Leipzig	Germany	04103
29	University Hospital Mannheim - Dep. of Medicine I	Mannheim	Germany	68167
30	University Hospital Munich - Dep. of Internal Medicine	Munich	Germany	80336
31	University Hospital Munich - Dep. of Anaesthesiology	Munich	Germany	81377
32	Hospital Munich Harlaching - Dep. of Internal Acute Medicine and Prevention	Munich	Germany	81545
33	Krankenhaus München-Neuperlach - Dep. of Anesthesiology	München	Germany	81737
34	University Hospital Münster - Dep. of Anesthesiology and Intensive Care Medicine	Münster	Germany	48149
35	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