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

• ICU length of stay [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  After 3 months from enrollment, the participant's ICU length of stay will be evaluated.
• Mortality at hospital discharge [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  After 3 months from enrollment, the participant's in hospital mortality will be evaluated.
• Development of the new infection [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  After 3 months from enrollment, the development of new infection of the participant during the hospitalization will be evaluated.
• Serum selenium level [ Time Frame: At 0, 24, 72, 168 hours post-enrollment ] [ Designated as safety issue: No ]
  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.
• Ventilator days [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  After 3 months from enrollment, total numbers of ventilator days of the participant during the hospitalization will be evaluated.
• Renal replacement therapy days [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  After 3 months from enrollment, the days of renal replacement therapy of the participant during the hospitalization will be evaluated.
• Oxidative stress marker [ Time Frame: At 0, 24, 72, 168 hours post-enrollment ] [ Designated as safety issue: No ]
  After study completion, serum glutathione peroxidase, reduced glutathione, NADPH, and MDA will be measured from stored samples.
• Changes in severity scores [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  APACHE II score, SOFA score, and SAPS II will be calculated at 1, 3, 7 days
• 3-month mortality [ Time Frame: 3 months post-enrollment ] [ Designated as safety issue: No ]
• Inflammatory markers [ Time Frame: At 0, 24, 72, 268 hours post-enrollment ] [ Designated as safety issue: No ]
  After study completion, serum cytokines, CRP, and chemokines will be measured from stored samples.
• Vasopressor days [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  Days of dopamine, norepinephrine, dobutamine, vasopressin, and epinephrine will be investigated

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.

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.

• Sepsis
• Shock, Septic

• 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 Name: Selenase T pro injectione
• 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 Name: Normal saline

• Experimental: Selenium
  500 mcg of selenium (10mL) daily for 7 days
  Intervention: Dietary Supplement: selenium replacement
• Placebo Comparator: Placebo
  Placebo 10 mL (delivered from biosyn) for 7 days
  Intervention: Dietary Supplement: Placebo

• Angstwurm MW, Engelmann L, Zimmermann T, Lehmann C, Spes CH, Abel P, Strauss R, Meier-Hellmann A, Insel R, Radke J, Schüttler J, Gärtner 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.
• 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.

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

• Biosyn
• Boryung Pharmaceutical Co., Ltd