Selenium Replacement and Serum Selenium Level in Severe Sepsis and Septic Shock Patients (SEREAL)

Effects of Selenium Replacement on Prognosis of Severe Sepsis and Septic Shock Patients and Their Initial Serum Selenium Level: a Randomized, Double-blind Placebo Controlled Phase 2 Study

This study will be performed to determine whether selenium replacement reduces 28-day mortality of severe sepsis and septic shock patients, and to investigate whether selenium replacement contributes differently to the mortality reduction of the patients according to their initial serum selenium level.

Study Overview

• Status: Withdrawn
• Conditions: Sepsis; Shock, Septic
• Intervention / Treatment: Dietary supplement: selenium replacement; Dietary supplement: Placebo

Detailed Description

This study is a single center, randomized, double-blind, placebo controlled trial.

After the diagnosis of severe sepsis and septic shock, enrolled patients will be randomized. Then, selenium or placebo will be intravenously administered to them for 7 days. Hemodynamic and laboratory data will be recorded for 7 days and additional serum samples will be obtained at 0, 24, 72, and 168 hours post-treatment and stored. Mortality will be observed for 28 days.

An interim analysis will be conducted by the independent data safety monitoring board.

Serum selenium levels will be measured from the stored serum samples after the study completion.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18 or older
• clinical diagnosis of severe sepsis or septic shock

Exclusion Criteria:

• pregnancy or breast feeding
• age younger than 18
• advanced directive state to withhold treatment
• known allergy to selenium
• CPR or death within 24 hours after the diagnosis of severe sepsis or septic shock
• advanced malignancy without further treatment plan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Selenium; 500 mcg of selenium (10mL) daily for 7 days	Dietary supplement: selenium replacement; Selenium 500 mcg (10 mL) mixed to 230 mL of normal saline will be infused continuously per day (10 mL/hour). Study drugs will be infused for 7 days.; Other Names: Selenase T pro injectione
PLACEBO_COMPARATOR: Placebo; Placebo 10 mL (delivered from biosyn) for 7 days	Dietary supplement: Placebo; placebo (10 mL) mixed to 230 mL of normal saline will be infused continuously per day (10 mL/hour). Study drugs will be infused for 7 days.; Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality	All cause mortality occurs within 28 days.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU length of stay	After 3 months from enrollment, the participant's ICU length of stay will be evaluated.	3 months
Mortality at hospital discharge	After 3 months from enrollment, the participant's in hospital mortality will be evaluated.	3 months
Development of the new infection	After 3 months from enrollment, the development of new infection of the participant during the hospitalization will be evaluated.	3 months
Serum selenium level	After study completion, serum selenium level will be measured from stored samples. Then, we will investigate whether selenium replacement contributes differently to the mortality reduction of the enrolled patients according to their initial serum selenium level.	At 0, 24, 72, 168 hours post-enrollment
Ventilator days	After 3 months from enrollment, total numbers of ventilator days of the participant during the hospitalization will be evaluated.	3 months
Renal replacement therapy days	After 3 months from enrollment, the days of renal replacement therapy of the participant during the hospitalization will be evaluated.	3 months
Oxidative stress marker	After study completion, serum glutathione peroxidase, reduced glutathione, NADPH, and MDA will be measured from stored samples.	At 0, 24, 72, 168 hours post-enrollment
Changes in severity scores	APACHE II score, SOFA score, and SAPS II will be calculated at 1, 3, 7 days	7 days
3-month mortality		3 months post-enrollment
Inflammatory markers	After study completion, serum cytokines, CRP, and chemokines will be measured from stored samples.	At 0, 24, 72, 268 hours post-enrollment
Vasopressor days	Days of dopamine, norepinephrine, dobutamine, vasopressin, and epinephrine will be investigated	3 months

Collaborators and Investigators

• Sponsor: Gil Joon Suh
• Collaborators: Biosyn; Boryung Pharmaceutical Co., Ltd
• Investigators: Principal Investigator: Gil Joon Suh, professor, Seoul National University Hospital

Publications and helpful links

General Publications

• Angstwurm MW, Engelmann L, Zimmermann T, Lehmann C, Spes CH, Abel P, Strauss R, Meier-Hellmann A, Insel R, Radke J, Schuttler J, Gartner R. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med. 2007 Jan;35(1):118-26. doi: 10.1097/01.CCM.0000251124.83436.0E.
• Andrews PJ, Avenell A, Noble DW, Campbell MK, Croal BL, Simpson WG, Vale LD, Battison CG, Jenkinson DJ, Cook JA; Scottish Intensive care Glutamine or seleNium Evaluative Trial Trials Group. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ. 2011 Mar 17;342:d1542. doi: 10.1136/bmj.d1542.
• Forceville X, Laviolle B, Annane D, Vitoux D, Bleichner G, Korach JM, Cantais E, Georges H, Soubirou JL, Combes A, Bellissant E. Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Crit Care. 2007;11(4):R73. doi: 10.1186/cc5960.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (ANTICIPATED): April 1, 2014
• Study Completion (ANTICIPATED): May 1, 2014

Study Registration Dates

• First Submitted: May 15, 2012
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (ESTIMATE): May 18, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 4, 2016
• Last Update Submitted That Met QC Criteria: March 3, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Survival; Sepsis; Shock, Septic; Selenium
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Shock, Septic; Shock; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Trace Elements; Micronutrients; Antioxidants; Selenium
• Other Study ID Numbers: SNUHEM-SEREAL-12-0001