Severe Sepsis and Septic Shock

Primary Objectives: To assess the efficacy of Rexis® as an add-on therapy in severe sepsis or septic shock patients Secondary Objectives: To evaluate the safety of Rexis® as an add-on therapy in severe sepsis or septic shock patients

Rexis®

Sodium Selenite Pentahydrate (SSP)

Injection

50 mcg of Selenium/mL

1. Primary endpoint:
28-day all-cause mortality
2. Secondary endpoints:
(1) 7-day, 14-day, and 21-day all-cause mortality
(2) ICU mortality
(3) 28-day all-cause mortality in subjects with low selenium level at baseline
3. Tertiary endpoints:
(1) Hospital mortality
(2) Mean changes from baseline (on day -1) in total SOFA score on days 1, 7, 14, 21, and 28.
Score will be recorded if subjects are still hospitalized on day 28.
(3) Length of ICU stay, length of hospital stay, number of ventilator days, development of new
infections during treatment period, duration of antimicrobial therapy.
(4) Serum selenium/selenite level and serum glutathione peroxidase (GPx3) levels return
within the normal range. The samples are to be collected at pre-dose (day -1), and on days
1, 3, 7, 10, and 14. The samples will be collected at the end of daily infusion of these
specified days. Two( 2) additional time points on days 21 and 28 if subjects are still being
hospitalized.
(5) EuroQoL Questionnaire-5 Dimensions 3 Level Version (EQ-5D-3L) on days 1 and 28,
when subjects discharge from hospital before day 28, only phone interview for EQ-5D-3L
on day 28 will be performed

Main inclusion criteria:
(1) Age  20 years
(2) Meet the criteria of either severe sepsis or septic shock (see below).
(3) From the diagnosis of severe sepsis or septic shock to drug administration ≤ 48 hours
(4) Life expectancy  72 hours
(5) Adequate placement of the central venous catheter for simultaneously administration of
Rexis® and concomitant therapy

Main exclusion criteria:
(1) Known allergy to selenium
(2) Expected to be in a chronic vegetative state or having pre-existing uncorrectable medical
condition with life expectancy < 28 days, include or suspected to have malignant
neoplasms or end-stage diseases.
(3) Undergoing ECMO treatment
(4) Undergoing regular hemodialysis or peritoneal dialysis treatment (including any
continuous renal replacement therapy such as CAVH or CVVH)
(5) Having severe head trauma or intracerebral hemorrhage (ICH)
(6) Known human immunodeficiency virus (HIV) infection
(7) Patients with granulocyte counts < 1000/mm3
not due to sepsis
(8) Has history of moderate to severe chronic heart failure (defined by New York Heart
Association Functional Classification III or IV) or has documented or suspected prior
myocardial infarction (MI) within the last 6 weeks:
Criteria for the diagnosis of prior MI:
(i) Pathological Q waves with or without symptoms in the absence of non-ischemic
causes
(ii) Imaging evidence of a region of loss of viable myocardium that is thinned and fails to
contract, in the absence of a non-ischemic cause
(iii) Pathological findings of a prior MI
(9) Body weight ≥ 150 kg at admission
(10) CPR treated within the previous 4 weeks
(11) Sepsis due to or to be suspected due to surgical complications
(12) Third-degree burns (within the previous 7 days) covering > 20% of body surface area
(13) History of receiving or undergoing organ transplantation or immune disorders that require
continuous immunosuppressant agent therapy
(14) Under anti-cancer medication or malignant primary disease as the cause of SIRS or sepsis,
for example, agranulocytosis as a result of chemotherapy or idiopathic bone marrow
aplasia.
(15) Pregnant or breast-feeding women
(16) Currently participating in any other clinical study or have participated in clinical trial
within the last 30 days
(17) Participants without informed consent or agreed with statement of "Do Not Resuscitate" or
"Do Not Treat"