Immuno Nutrition by L-citrulline for Critically Ill Patients (Immunocitre)

The main objective of this study is to demonstrate that the only administration of L-citrulline, can improve immune functions in critically ill patients at high risk of nosocomial infection.

Study Overview

• Status: Completed
• Conditions: Intubation; Pulmonary Ventilation
• Intervention / Treatment: Dietary supplement: Placebo; Procedure: Enteral nutrition; Dietary supplement: L-Citrulline

Detailed Description

This is a multicentric therapeutic trial, randomized and double blind: standard enteral nutrition plus L-citrulline (5 grams/12 Hours for 5 days from the admission in Intensive Care Unit (ICU)) versus standard enteral nutrition plus placebo.

Methods-Patients: Non-surgical patients admitted in medical intensive care unit, under mechanical ventilation for an expected duration > 2 days, without severe sepsis or septic shock, will be enrolled. Symptoms leading for ICU admission ongoing for five days maximum. On admission (before treatment), the severity will be evaluated with the Sepsis-related Organ Failure Assessment (SOFA) score together with an assessment of plasmatic arginine, cytokines (InterLeukin-6 (IL6) ), and expression of Human Leukocyte Antigen - antigen D Related (HLA-DR) by monocytes. The same evaluation will be repeated on day 3 (during treatment) and on day 7 (after treatment).

The enrolment of 100 patients is statistically enough to demonstrate a decreased SOFA scores in the L-citrulline group as compared to the placebo group on day 7.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU Angers
  • Nantes, France
    • CHU Nantes
  • Paris, France
    • Paris - HEGP
  • Rennes, France, 35033
    • Rennes Hospital University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age > 18 years
• medical patient (absence of recent surgery or trauma)
• initial aggression < 5 days
• mechanically ventilated with expected duration of mechanical ventilation > 2 days
• exclusive enteral nutrition
• absence of previous immunosuppression

Exclusion Criteria:

• severe sepsis
• septic shock
• obesity defined as BMI above 40
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-Citrulline group; Enteral nutrition 5-day L-citrulline treatment (10 grams/day)	Procedure: Enteral nutrition; Dietary supplement: L-Citrulline
Placebo Comparator: Control group; Enteral nutrition 5-day placebo treatment	Dietary supplement: Placebo; Procedure: Enteral nutrition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ failure score comparison D7	Organ failure score (SOFA score) on day 7 in the L-citrulline group as compared to the placebo group	At day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ failure score comparison D3	Organ failure score (SOFA score) on day 3 in the L-citrulline group as compared to the placebo group	At day 3
SOFA score evolution between randomisation and D7	Binary criterion of success or failure : - Success is defined by: an improved SOFA score of at least 2 points from randomization to Day 7 or an improvement in the general condition yielding the release of the unit; - Failure is defined by an improved SOFA score but less than 2 points, no improvement or worsening of the SOFA score from randomization to Day 7 or the patient's death before J7;	up to 7 days
Expression of HLA-DR	Expression of HLA-DR in the L-citrulline group as compared to the placebo group	At day 7
Plasmatic concentration of IL6	Comparison of the plasmatic concentration of interleukin-6 between the L-citrulline group and the placebo group	At day 7
HLA-DR	Comparison of the percentage of expression of monocytic HLA-DR between the L-citrulline group and the placebo group	At day 7
Plasmatic concentration of L-arginine	Comparison of the plasmatic concentration of L-arginine and its metabolites between the L-citrulline group and the placebo group	At day 7
Incidence of nosocomial infections	Comparison between the L-citrulline group and the placebo group	during the stay in the ICU, an average of 7 days
Length of stay	Length of stay in ICU and hospital: Comparison between the L-citrulline group and the placebo group	during the stay in hospital, up to 28 days
Mortality	Mortality in intensive care and in hospital : Comparison between the L-citrulline group and the placebo group; Duration of mechanical ventilation.	during the stay in hospital, up to 28 days
Duration of mechanical ventilation	Duration of mechanical ventilation: Comparison between the L-citrulline group and the placebo group	during the stay in ICU, an average of 7 days

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Jean-Marc TADIE, MD, CHU Rennes

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 8, 2016
• First Posted (Estimate): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: 35RC14_9835; 2015-A00961-48 (Other Identifier: Id-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No