Selenium Replacement and Serum Selenium Level in Severe Sepsis and Septic Shock Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Sepsis, Shock, Septic

Intervention / Treatment
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* Dietary Supplement: selenium replacement
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selenium<br>500 mcg of selenium (10mL) daily for 7 days | Dietary Supplement: selenium replacement<br>* 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.<br>* Other names: Selenase T pro injectione;|
| Placebo Comparator: Placebo<br>Placebo 10 mL (delivered from biosyn) for 7 days | Dietary Supplement: Placebo<br>* 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.<br>* Other names: Normal saline;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Shock, Septic, Selenium, Survival