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

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

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Severe Sepsis
• Intervention / Treatment: Drug: Selenium as sodium selenite

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 Type: Interventional
• Enrollment: 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Argenteuil, France, 95107
    • Service de Réanimation - Centre Hospitalier Victor Dupouy
  • Châlons-en-Champagne, France, 51000
    • Service de Réanimation Polyvalente - CH de Châlons
  • Garches, France, 92380
    • Service de Réanimation Médicale - Hôpital Raymond Poincaré
  • Lyon, France, 69275
    • Service de Réanimation - HIA Desgenettes
  • Meaux, France, 77104
    • Service de Réanimation Polyvalente - Hôpital Saint Faron
  • Toulon, France, 83800
    • Service Réanimation - HIA Saint Anne
  • Tourcoing, France, 59208
    • Service de Réanimation - Centre Hospitalier G. Dron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Weaning time of catecholamines

Secondary Outcome Measures

Outcome Measure
- 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

Collaborators and Investigators

• Sponsor: Centre Hospitalier de Meaux
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Xavier Forceville, MD, CH Meaux

Publications and helpful links

General Publications

• Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, Mercier JC, Offenstadt G, Regnier B. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA. 1995 Sep 27;274(12):968-74.
• Forceville X, Vitoux D, Gauzit R, Combes A, Lahilaire P, Chappuis P. Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients. Crit Care Med. 1998 Sep;26(9):1536-44. doi: 10.1097/00003246-199809000-00021.
• Goode HF, Webster NR. Free radicals and antioxidants in sepsis. Crit Care Med. 1993 Nov;21(11):1770-6. doi: 10.1097/00003246-199311000-00029.
• Novelli GP. Role of free radicals in septic shock. J Physiol Pharmacol. 1997 Dec;48(4):517-27.
• 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. doi: 10.1186/cc5960.

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Study Completion: January 1, 2005

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 21, 2005

Study Record Updates

• Last Update Posted (Estimate): September 21, 2005
• Last Update Submitted That Met QC Criteria: September 13, 2005
• Last Verified: September 1, 2005

More Information

Terms related to this study

• Keywords: Oxidative stress; Septic shock; Selenium; Sodium selenite
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Trace Elements; Micronutrients; Antioxidants; Selenious Acid; Sodium Selenite; Selenium
• Other Study ID Numbers: AFSSAPS 10602; CIC0203/003