Clinical trial NCT00207844: Selenium, as Sodium Selenite, in the Treatment of Septic Shock
Official title: Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating Efficacy and Safety of a Therapeutic Administration of Selenium, as Selenite, in Septic Shock Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Septic Shock
Severe Sepsis
Keywords: Selenium
Oxidative stress
Septic shock
Sodium selenite
Lead sponsor: Centre Hospitalier de Meaux
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2005-09-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Weaning time of catecholamines
Secondary outcomes:
measure: - 6 month mortality rate
measure: - 6 month quality of life
measure: - 28 days mortality
measure: - ICU mortality
measure: - Hospital mortality
measure: - ICU length of stay
measure: - Hospital length of stay
measure: - Number of nosocomial infections in ICU
measure: - Duration of ventilation
measure: - SOFA score in ICU at days 4, 7, 10 and 14
measure: - Oxidative stress evaluation at days 4, 7, 10 and 14
measure: - Inflammation evaluation at days 4, 7, 10 and 14
measure: - Selenium status
measure: - Costs and work load
measure: - Onset of clinical events
Other outcomes:
Locations:
city: Argenteuil
country: France
facility: Service de Réanimation - Centre Hospitalier Victor Dupouy
city: Châlons-en-Champagne
country: France
facility: Service de Réanimation Polyvalente - CH de Châlons
city: Garches
country: France
facility: Service de Réanimation Médicale - Hôpital Raymond Poincaré
city: Lyon
country: France
facility: Service de Réanimation - HIA Desgenettes
city: Meaux
country: France
facility: Service de Réanimation Polyvalente - Hôpital Saint Faron
city: Toulon
country: France
facility: Service Réanimation - HIA Saint Anne
city: Tourcoing
country: France
facility: Service de Réanimation - Centre Hospitalier G. Dron
Study officials:
affiliation: CH Meaux
name: Xavier Forceville, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Rennes
name: Eric Bellissant, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: Novelli GP. Role of free radicals in septic shock. J Physiol Pharmacol. 1997 Dec;48(4):517-27.
citation: 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.