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

Phase 3CompletedNCT00832039

Kompetenznetz Sepsis1,089 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Conditions

Severe Sepsis Septic Shock

Interventions

sodium-seleniteDRUG

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.

PlaceboDRUG

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 therapyPROCEDURE

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (35)

Outcomes

Primary Outcomes

All cause mortality

Time frame: 28 days

Secondary Outcomes

Mean total SOFA and SOFA subscores

Time frame: study duration

All cause mortality

Time frame: 90 days

Frequency and duration of mechanical ventilation

Time frame: 90 days

Frequency and duration of vasopressor support

Time frame: 90 days

Frequency of adverse events and severe adverse events

Time frame: study duration

Clinical cure and microbiological cure

Time frame: days 4, 7, 10, 14

Duration of antimicrobial therapy

Time frame: study duration

Costs of antimicrobial therapy

Time frame: study duration

Time to change of antibiotic therapy

Time frame: duration of study

Days alive without antimicrobial therapy

Time frame: study duration

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

Time frame: study duration

Data from ClinicalTrials.gov

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