IntubationImmunocitreNCT02864017
Immuno Nutrition by L-citrulline for Critically Ill Patients
A study testing Enteral nutrition and L-Citrulline in people with Intubation and Pulmonary Ventilation, run by Rennes University Hospital at 4 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intubation, Pulmonary Ventilation
- What is being tested?
- Enteral nutrition and L-Citrulline
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 4 sitesFrance
- Study dates
- Sep 2016to Apr 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- severe sepsis
- septic shock
- obesity defined as BMI above 40
- pregnancy
Trial locations and contacts
4 sites in 1 country.
France4 sites
CHU Angers
Angers
CHU Nantes
Nantes
Paris - HEGP
Paris
Rennes Hospital University
Rennes, 35033
About this study
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.
Read the 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.
- Conditions
- Intubation, Pulmonary Ventilation
- Being tested
- Enteral nutrition, L-Citrulline, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enteral nutritionProcedure or surgery
L-CitrullineDietary supplement
PlaceboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| L-Citrulline group | Experimental | Enteral nutrition 5-day L-citrulline treatment (10 grams/day) Receives: Procedure: Enteral nutrition; Dietary Supplement: L-Citrulline |
| Control group | Placebo comparator | Enteral nutrition 5-day placebo treatment Receives: Procedure: Enteral nutrition; Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Organ failure score comparison D7
Organ failure score (SOFA score) on day 7 in the L-citrulline group as compared to the placebo group
Measured: At day 7
Secondary outcomes (10)
Organ failure score comparison D3
Organ failure score (SOFA score) on day 3 in the L-citrulline group as compared to the placebo group
Measured: 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;
Measured: up to 7 days
Expression of HLA-DR
Expression of HLA-DR in the L-citrulline group as compared to the placebo group
Measured: At day 7
Plasmatic concentration of IL6
Comparison of the plasmatic concentration of interleukin-6 between the L-citrulline group and the placebo group
Measured: At day 7
HLA-DR
Comparison of the percentage of expression of monocytic HLA-DR between the L-citrulline group and the placebo group
Measured: 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
Measured: At day 7
Incidence of nosocomial infections
Comparison between the L-citrulline group and the placebo group
Measured: 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
Measured: 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.
Measured: 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
Measured: during the stay in ICU, an average of 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2016 (estimated)
- Study startSep 2016
- Primary completionApr 2019
- Study completionApr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for IntubationStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Marc TADIE, MD, Principal investigator, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02864017
- Sponsor's protocol ID
- 35RC14_9835
- Other IDs
- 2015-A00961-48
- Acronym
- Immunocitre
- Status last verified
- Jun 2020
- First submitted
- 4 Aug 2016
- Last updated
- 9 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Maamar A, Gacouin A, Reignier J, Asfar P, Commereuc M, Lesouhaitier M, Gregoire M, Le Pabic E, Bendavid C, Moreau C, Thibault R, Terzi N, Delclaux C, Laviolle B, Tadie JM. What a negative trial does not tell us: Bayesian reanalysis of the enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients randomized clinical trial. Clin Nutr ESPEN. 2026 Sep 17:105113. doi: 10.1016/j.clnesp.2026.105113. Online ahead of print.
PubMed 42753870Tadie JM, Locher C, Maamar A, Reignier J, Asfar P, Commereuc M, Lesouhaitier M, Gregoire M, Le Pabic E, Bendavid C, Moreau C, Diehl JL, Gey A, Tartour E, Le Tulzo Y, Thibault R, Terzi N, Gacouin A, Roussel M, Delclaux C, Tarte K, Cynober L. Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial. Crit Care. 2023 Oct 3;27(1):381. doi: 10.1186/s13054-023-04651-y.
PubMed 37784110
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immuno Nutrition by L-citrulline for Critically Ill Patients
- ClinicalTrials.gov ID
- NCT02864017
- Acronym / sponsor ID
- Immunocitre / 35RC14_9835
- Conditions
- Intubation, Pulmonary Ventilation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- Apr 2019 (actual)
- Study completion
- Apr 2020 (actual)
- First posted
- 11 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-Citrulline group | Experimental | Procedure: Enteral nutrition, Dietary Supplement: L-CitrullineEnteral nutrition 5-day L-citrulline treatment (10 grams/day) |
| Control group | Placebo comparator | Procedure: Enteral nutrition, Dietary Supplement: PlaceboEnteral nutrition 5-day placebo treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- severe sepsis
- septic shock
- obesity defined as BMI above 40
- pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enteral nutrition | Procedure or surgery | Control group, L-Citrulline group |
| L-Citrulline | Dietary supplement | L-Citrulline group |
| Placebo | Dietary supplement | Control group |
Primary outcome
Organ failure score comparison D7
Time frame: At day 7
Organ failure score (SOFA score) on day 7 in the L-citrulline group as compared to the placebo group
10 secondary outcomes
Organ failure score comparison D3
Time frame: At day 3
SOFA score evolution between randomisation and D7
Time frame: up to 7 days
Expression of HLA-DR
Time frame: At day 7
Plasmatic concentration of IL6
Time frame: At day 7
HLA-DR
Time frame: At day 7
Plasmatic concentration of L-arginine
Time frame: At day 7
Incidence of nosocomial infections
Time frame: during the stay in the ICU, an average of 7 days
Length of stay
Time frame: during the stay in hospital, up to 28 days
Mortality
Time frame: during the stay in hospital, up to 28 days
Duration of mechanical ventilation
Time frame: during the stay in ICU, an average of 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
- Derived from this study: PubMed 42753870Maamar A, Gacouin A, Reignier J, Asfar P, Commereuc M, Lesouhaitier M, Gregoire M, Le Pabic E, Bendavid C, Moreau C, Thibault R, Terzi N, Delclaux C, Laviolle B, Tadie JM. What a negative trial does not tell us: Bayesian reanalysis of the enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients randomized clinical trial. Clin Nutr ESPEN. 2026 Sep 17:105113. doi: 10.1016/j.clnesp.2026.105113. Online ahead of print.
- Derived from this study: PubMed 37784110Tadie JM, Locher C, Maamar A, Reignier J, Asfar P, Commereuc M, Lesouhaitier M, Gregoire M, Le Pabic E, Bendavid C, Moreau C, Diehl JL, Gey A, Tartour E, Le Tulzo Y, Thibault R, Terzi N, Gacouin A, Roussel M, Delclaux C, Tarte K, Cynober L. Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial. Crit Care. 2023 Oct 3;27(1):381. doi: 10.1186/s13054-023-04651-y.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Marc TADIE, MD principal investigator
Rennes University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Enteral nutrition and L-Citrulline in people with Intubation and Pulmonary Ventilation, run by Rennes University Hospital at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Organ failure score comparison D7 (time frame: At day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02864017, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2020.