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

Septic Shock Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00207844
• Other study ID #: AFSSAPS 10602
• Secondary ID: CIC0203/003
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2005
• Last updated: September 13, 2005
• Start date: January 2002
• Est. completion date: January 2005

Study information

• Verified date: September 2005
• Source: Centre Hospitalier de Meaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Septic Shock
• Severe Sepsis
• Shock
• Shock, Septic

Intervention

Drug:
• Selenium as sodium selenite

Locations

Country	Name	City	State
France	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

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier de Meaux	Ministry of Health, France

Country where clinical trial is conducted

France, 

References & Publications (4)

Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, Mercier JC, Offenstadt G, Régnier 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. — View 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. — View Citation

Goode HF, Webster NR. Free radicals and antioxidants in sepsis. Crit Care Med. 1993 Nov;21(11):1770-6. Review. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weaning time of catecholamines
Secondary	- 6 month mortality rate
Secondary	- 6 month quality of life
Secondary	- 28 days mortality
Secondary	- ICU mortality
Secondary	- Hospital mortality
Secondary	- ICU length of stay
Secondary	- Hospital length of stay
Secondary	- Number of nosocomial infections in ICU
Secondary	- Duration of ventilation
Secondary	- SOFA score in ICU at days 4, 7, 10 and 14
Secondary	- Oxidative stress evaluation at days 4, 7, 10 and 14
Secondary	- Inflammation evaluation at days 4, 7, 10 and 14
Secondary	- Selenium status
Secondary	- Costs and work load
Secondary	- Onset of clinical events