Probiotic Enteral Administration in Mechanically Ventilated Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Enterally Administered Probiotics in Mechanically Ventilated Patients: Double-Blind, Prospective Randomized Study Versus Placebo

Conditions
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Pneumonia

Intervention / Treatment
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* Dietary Supplement: Ergyphilus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients under mechanical ventilation for at least 48 hours Exclusion Criteria: Age under 18 Pregnancy Immunocompromised status Short bowel disease Moribund condition

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Dietary Supplement: Ergyphilus<br>* 5 pills a day of Ergyphilus or placebo<br>|
| Placebo Comparator: 2<br> | Dietary Supplement: Ergyphilus<br>* 5 pills a day of Ergyphilus or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensive Care Unit (ICU) mortality rate |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital mortality rate |  | 60 days | 
| incidence of ventilator-associated pneumonia |  | 28 days | 
| incidence of multi-resistant bacteria infection and colonization |  | 28 days | 
| incidence of diarrhea |  | 28 days | 
| ICU length of stay |  | 60 days | 
| hospital length of stay |  | 60 days | 
| antibiotic use in ICU (antibiotic-free days) |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ventilator-associated pneumonia, probiotic, mechanical ventilation, intensive care