Intubation, Pulmonary Ventilation
Conditions
Brief summary
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.
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.
Interventions
PROCEDUREEnteral nutrition
DIETARY_SUPPLEMENTL-Citrulline
DIETARY_SUPPLEMENTPlacebo
Sponsors
Rennes University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Organ failure score comparison D7 | At day 7 | Organ failure score (SOFA score) on day 7 in the L-citrulline group as compared to the placebo group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SOFA score evolution between randomisation and D7 | up to 7 days | 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; |
| Expression of HLA-DR | At day 7 | Expression of HLA-DR in the L-citrulline group as compared to the placebo group |
| Plasmatic concentration of IL6 | At day 7 | Comparison of the plasmatic concentration of interleukin-6 between the L-citrulline group and the placebo group |
| HLA-DR | At day 7 | Comparison of the percentage of expression of monocytic HLA-DR between the L-citrulline group and the placebo group |
| Organ failure score comparison D3 | At day 3 | Organ failure score (SOFA score) on day 3 in the L-citrulline group as compared to the placebo group |
| Incidence of nosocomial infections | during the stay in the ICU, an average of 7 days | Comparison between the L-citrulline group and the placebo group |
| Length of stay | during the stay in hospital, up to 28 days | Length of stay in ICU and hospital: Comparison between the L-citrulline group and the placebo group |
| Mortality | during the stay in hospital, up to 28 days | * Mortality in intensive care and in hospital : Comparison between the L-citrulline group and the placebo group * Duration of mechanical ventilation. |
| Duration of mechanical ventilation | during the stay in ICU, an average of 7 days | Duration of mechanical ventilation: Comparison between the L-citrulline group and the placebo group |
| Plasmatic concentration of L-arginine | At day 7 | Comparison of the plasmatic concentration of L-arginine and its metabolites between the L-citrulline group and the placebo group |
Countries
France
Outcome results
None listed