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

Sepsis Clinical Trial

— SEREAL  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01601938
• Other study ID #: SNUHEM-SEREAL-12-0001
• Status: Withdrawn
• Phase: Phase 2
• First received: May 15, 2012
• Last updated: March 3, 2016
• Start date: September 2012
• Est. completion date: May 2014

Study information

• Verified date: March 2016
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Shock
• Shock, Septic
• Toxemia

Intervention

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.
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (3)

Lead Sponsor	Collaborator
Gil Joon Suh	Biosyn, Boryung Pharmaceutical Co., Ltd

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	28-day mortality	All cause mortality occurs within 28 days.	28 days	No
Secondary	ICU length of stay	After 3 months from enrollment, the participant's ICU length of stay will be evaluated.	3 months	No
Secondary	Mortality at hospital discharge	After 3 months from enrollment, the participant's in hospital mortality will be evaluated.	3 months	No
Secondary	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	No
Secondary	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	No
Secondary	Ventilator days	After 3 months from enrollment, total numbers of ventilator days of the participant during the hospitalization will be evaluated.	3 months	No
Secondary	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	No
Secondary	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	No
Secondary	Changes in severity scores	APACHE II score, SOFA score, and SAPS II will be calculated at 1, 3, 7 days	7 days	No
Secondary	3-month mortality		3 months post-enrollment	No
Secondary	Inflammatory markers	After study completion, serum cytokines, CRP, and chemokines will be measured from stored samples.	At 0, 24, 72, 268 hours post-enrollment	No
Secondary	Vasopressor days	Days of dopamine, norepinephrine, dobutamine, vasopressin, and epinephrine will be investigated	3 months	No

External Links

•   Our preliminary observational study which shows low serum selenium level was associated with poor prognosis of patients with septic shock in Korea.