Selenium, as Sodium Selenite, in the Treatment of Septic Shock

Study Overview
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Brief Summary
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Septic shock is a frequent syndrome with a 45% mortality rate despite intensive care unit (ICU) care, where free radicals may play a key role, and a >40% decrease in plasma selenium concentration is observed. Selenium is a trace element with both indirect enzymatic anti-oxidant, and direct oxidant properties. High dose of sodium selenite administration could increase antioxidant cells capacities, and reduce inflammation by a direct paradoxical pro-oxidative effect. We conduct a study to evaluate the effects of selenium treatment in comparison to placebo, in septic shock patients. Efficacy will be evaluated by the weaning time of catecholamines.

Detailed Description
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Septic shock - an uncontrolled systemic host response to invasive infection -, leading to multiple organ failure, is a public health issue because of its frequency (> 1/1000 inhabitants per year), its cost and its 45% mortality rate, remaining high despite all the improvements made in ICU for the past 20 years. His physiopathology is better understood with increasing data supporting the key role of free radicals, and a more than 40% plasma selenium concentration decrease that maybe associated with increased morbidity and mortality. Meanwhile, for the past 30 years, researches have been conducted on the essential trace element selenium for its requirement for key antioxidant enzymes, through the 21st aa selenocystein, and also for its potentially toxic, pro-oxidant properties. In septic shock, both properties may be useful, antioxidant enzymatic to increase cell defense especially endothelial cells, and direct pro-oxidant action to decrease the genomic response, especially on phagocytic cells. The objective of this study is to evaluate the effects of a high dose of selenium administration, such as selenite, at pro-oxydant initial dose followed by anti-oxidant dose in severe septic shock patients with documented infection. The initial dose was chosen as the highest dose of selenium, as sodium selenite, estimated without severe adverse effects in healthy people for a one-day ingestion. The patients are randomized to receive either the placebo or the selenite at this high initial dose followed by lower doses on a 9-day period. The efficacy will be evaluated by the weaning time of catecholamines, with a special attention to the 6-month mortality rate as first secondary end point.

Official Title
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Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating Efficacy and Safety of a Therapeutic Administration of Selenium, as Selenite, in Septic Shock Patients.

Conditions
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Septic Shock, Severe Sepsis

Intervention / Treatment
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* Drug: Selenium as sodium selenite


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalization in ICU Severe documented infection Ventilation Circulatory failure requiring high dose of catecholamine IGS II score >25 at inclusion Informed written consent Exclusion Criteria: Pregnancy End phase chronic disease Limitation of care Shock due to an urinary infection without bacteriemia Peritonitis related to peritoneal dialysis or trauma Preliminary circulatory failure Participating to another clinical trial

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: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Selenium as sodium selenite|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weaning time of catecholamines |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - 6 month mortality rate |  |  | 
| - 6 month quality of life |  |  | 
| - 28 days mortality |  |  | 
| - ICU mortality |  |  | 
| - Hospital mortality |  |  | 
| - ICU length of stay |  |  | 
| - Hospital length of stay |  |  | 
| - Number of nosocomial infections in ICU |  |  | 
| - Duration of ventilation |  |  | 
| - SOFA score in ICU at days 4, 7, 10 and 14 |  |  | 
| - Oxidative stress evaluation at days 4, 7, 10 and 14 |  |  | 
| - Inflammation evaluation at days 4, 7, 10 and 14 |  |  | 
| - Selenium status |  |  | 
| - Costs and work load |  |  | 
| - Onset of clinical events |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Selenium, Oxidative stress, Septic shock, Sodium selenite