Clinical trial NCT00122408: Probiotic Enteral Administration in Mechanically Ventilated Patients
Official title: Effect of Enterally Administered Probiotics in Mechanically Ventilated Patients: Double-Blind, Prospective Randomized Study Versus Placebo
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pneumonia
Keywords: ventilator-associated pneumonia
probiotic
mechanical ventilation
intensive care
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2005-07-22
Enrollment: 740
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: The objective of this study is to assess the effects of a daily enteral supplementation with probiotics within a population of critically ill, mechanically ventilated patients. Especially, the effects of probiotics on mortality rate in intensive care medicine will be analysed.

Detailed description: In a critically ill patient, the gut integrity is rapidly compromised either by the treatments used (such as catecholamine or antibiotics) or by the disease itself. This gut alteration favours the adhesion and/or internalisation of bacteria by intestine cells which lead to the production of large amounts of cytokines that rapidly reach the blood compartment, inducing neutrophils activation and then organ damage. Moreover, the imbalance in the normal intestinal flora (demonstrated as early as 24 hours after ICU admission) is one of the mechanisms involved in the development of ventilator associated pneumonia (VAP). VAP is the leading cause of ICU-acquired infection and is responsible for prolonged ICU stay, increased mortality and costs. Probiotics, and especially Lactobacillus Rhamnosus GG ('LGG'), have been demonstrated to possess beneficial effects in terms of intestine flora imbalance and immune response.

Objective: To study the effects of a probiotic mixture (containing LGG) enteral administration on the survival and the incidence of VAP in mechanically ventilated patients.

Patients and Methods: Prospective, randomized, double-blind, placebo-controlled study. After randomization, 740 intubated patients with a predictive length of mechanical support of more than 48 hours will enterally receive either 10.10 cfu of probiotic (Ergyphilus, Nutergia, France) or a identical placebo daily until withdrawal of mechanical support. The main endpoint is the mortality rate in ICU. Secondary endpoints include hospital length of stay and mortality rate, VAP incidence and the number of days free from antibiotics. Length of the study 24 months.

Perspectives: The objective is to demonstrate a survival advantage due to LGG administration, along with a reduction of VAP episodes and antibiotic use.

Eligibility criteria: Inclusion Criteria:

* Patients under mechanical ventilation for at least 48 hours

Exclusion Criteria:

* Age under 18
* Pregnancy
* Immunocompromised status
* Short bowel disease
* Moribund condition

Primary outcomes:
measure: Intensive Care Unit (ICU) mortality rate
timeFrame: 28 days
Secondary outcomes:
measure: Hospital mortality rate
timeFrame: 60 days
measure: incidence of ventilator-associated pneumonia
timeFrame: 28 days
measure: incidence of multi-resistant bacteria infection and colonization
timeFrame: 28 days
measure: incidence of diarrhea
timeFrame: 28 days
measure: ICU length of stay
timeFrame: 60 days
measure: hospital length of stay
timeFrame: 60 days
measure: antibiotic use in ICU (antibiotic-free days)
timeFrame: 28 days
Other outcomes:
Locations:
city: Macon
country: France
facility: CHG
city: Metz
country: France
facility: CHR
city: Nancy
country: France
facility: Hopital Central, Service de Reanimation Medicale
Study officials:
affiliation: CHU NANCY
name: Sebastien Gibot, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: