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

Phase 2

Completed

• Conditions: Septic Shock; Severe Sepsis

• Registration Number: NCT00207844
• Lead Sponsor: Centre Hospitalier de Meaux

Brief Summary

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

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.

Study Timeline

• Study Start: 2002-01
• Study Completion: 2005-01
• Status Verified: 2005-09
• Study First Submitted: 2005-09-13
• Study First Submitted QC: 2005-09-13
• Last Update Submitted: 2005-09-13
• Study First Posted: 2005-09-21
• Last Update Posted: 2005-09-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Weaning time of catecholamines

Secondary Outcome Measures

Name	Time	Method
- Duration of ventilation
- 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
- 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

Trial Locations

Locations (7)

Service de Réanimation Polyvalente - Hôpital Saint Faron; 🇫🇷 Meaux, France

Service Réanimation - HIA Saint Anne; 🇫🇷 Toulon, France

Service de Réanimation - Centre Hospitalier G. Dron; 🇫🇷 Tourcoing, France

Service de Réanimation Polyvalente - CH de Châlons; 🇫🇷 Châlons-en-Champagne, France

Service de Réanimation - Centre Hospitalier Victor Dupouy; 🇫🇷 Argenteuil, France

Service de Réanimation Médicale - Hôpital Raymond Poincaré; 🇫🇷 Garches, France

Service de Réanimation - HIA Desgenettes; 🇫🇷 Lyon, France