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.

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.

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.

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.

After 3 months from enrollment, the development of new infection of the participant during the hospitalization will be evaluated.

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.

After 3 months from enrollment, total numbers of ventilator days of the participant during the hospitalization will be evaluated.

After 3 months from enrollment, the days of renal replacement therapy of the participant during the hospitalization will be evaluated.

After study completion, serum glutathione peroxidase, reduced glutathione, NADPH, and MDA will be measured from stored samples.

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

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