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

NCT ID: NCT00207844

Last Updated: 2005-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2005-01-31

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.

Conditions

Septic Shock; Severe Sepsis

Keywords

Selenium; Oxidative stress; Septic shock; Sodium selenite

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Selenium as sodium selenite

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Centre Hospitalier de Meaux

OTHER

Sponsor Role: lead

Principal Investigators

Xavier Forceville, MD

Role: PRINCIPAL_INVESTIGATOR

CH Meaux

Eric Bellissant, MD, PhD

Role: STUDY_CHAIR

CHU Rennes

Locations

Service de Réanimation - Centre Hospitalier Victor Dupouy

Argenteuil, , France

Service de Réanimation Polyvalente - CH de Châlons

Châlons-en-Champagne, , France

Service de Réanimation Médicale - Hôpital Raymond Poincaré

Garches, , France

Service de Réanimation - HIA Desgenettes

Lyon, , France

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

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 7674528 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9751590 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8222696 (View on PubMed)

Novelli GP. Role of free radicals in septic shock. J Physiol Pharmacol. 1997 Dec;48(4):517-27.

Reference Type: BACKGROUND

PMID: 9444605 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 17617901 (View on PubMed)

Other Identifiers

CIC0203/003

Identifier Type: -

Identifier Source: secondary_id

AFSSAPS 10602

Identifier Type: -

Identifier Source: org_study_id