Intensive Care UnitsCARSNCT03837730
Citrulline and Arginase Activity in Severe Sepsis and Septic Shock
An observational study of Intensive Care Units and Infection, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
Trial summary
Sepsis is an acute pathology defined as an inappropriate response of the host to infection, resulting in the onset of organ failure (Quick SOFA ≥2, or SOFA ≥2). Septic shock is a sepsis associated with an elevation of lactate ≥ 2 mmol / l and an arterial hypotension requiring vasoactive drugs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intensive Care Units, Infection, Biomarkers
- How many people
- 118 participants
- Where
- 1 siteFrance
- Study dates
- 28 May 2019to 30 Oct 2022
- Phase
- Observational
- 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
Study population: patients admitted to the ICU for severe sepsis or septic shock
Who may be able to join
- 18 years old or older
- Patient admitted to ICU
- Diagnosis, suspected or confirmed, of severe sepsis or septic shock
- Expected ICU stay of at least 2 days
- Affiliation to a social security system or recipient of a such system
- Signed informed consent
Who cannot join
- Pregnancy
- Chronic intestinal pathology
- Chronic renal failure defined by creatinine clearance <50 ml / min / 1.73m2 (CKD-EPI)
- Severe hepatic insufficiency (Child-Pugh stage C score)
- Legal incapacity or limited legal capacity
- Subject unlikely to cooperate with the study and / or weak cooperation anticipated by the investigator
- Patient within the exclusion period of another study or planned by the "national file of volunteers"
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Activity and Expression of Plasma Arginase in Patients With Severe Sepsis or Septic Shock as Prognostic Value
Sepsis is an acute pathology defined as an inappropriate response of the host to infection, resulting in the onset of organ failure (Quick SOFA ≥2, or SOFA ≥2). Septic shock is a sepsis associated with an elevation of lactate ≥ 2 mmol / l and an arterial hypotension requiring vasoactive drugs. Several studies highlighted that sepsis is associated with a plasma L-arginine deficiency. This deficiency induces a lower availability of L-arginine for multiple metabolic pathways including those involved in the synthesis of nitric oxide (NO) in the vascular endothelium via NO synthase. NO is the main endogenous vasodilator mediator, a lower synthesis induces a vascular and endothelial dysfunction that can promote the occurrence of an organic dysfunction during sepsis. Decrease in available NO was confirmed in patients with sepsis and appears correlated with severity.
L-arginine deficiency can have multiple origins:
Read more
- L-arginine deficiency resulting from a decrease in endogenous production from citrulline synthesized by the enterocytes. Such enterocyte dysfunction has been confirmed in patients with sepsis and is characterized biologically by elevated plasma levels of I-FABP (intestinal fatty acid binding protein - enterocyte-specific protein, cytolysis marker) and lower than that of citrulline (hypocitrullinemia, marker of lower activity).
- L-arginine deficiency may also result from a catabolism increase via arginase activity increased. This ubiquitous enzyme, having 2 isoforms (Arg1 and Arg2), allows the synthesis of urea and ornithine from L-arginine. An increase in arginase activity would decrease the available reserves of L-arginine for NO synthesis.
The objectives of this work is to evaluate, in patients with severe sepsis or septic shock, the prognostic value of the plasma arginase activity and the plasma expression of 2 isoforms Arg1 and Arg2, their kinetics, and the link between activity / expression of arginase and enterocyte dysfunction.
- Conditions
- Intensive Care Units, Infection, Biomarkers, Sepsis, Septic Shock
- Keywords
- ICU, sepsis, septic shok, arginase, citrulline
- Medical subject headings
- Infections, Sepsis, Shock, Septic
What is being measured
The primary outcome is the main question the study is designed to answer.
prognostic value of plasma arginase activity and expression at ICU admission in patients with severe sepsis or septic shock
activity / expression of plasma arginase at ICU admission and 28-day mortality rate from admission to intensive care
Measured: 28 days
Secondary outcomes (2)
activity / expression kinetic of plasma arginase
3 points kinetic : admission, day 3 and day 7
Measured: during the first 7 days of ICU admission
prognostic value of enterocyte damage
at ICU admission and 28-day mortality rate from admission to intensive care
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2019
- Study start28 May 2019
- Primary completion30 Sep 2022
- Study completion30 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intensive Care UnitsStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gaël PITON, MD, Principal investigator, CHU DE BESANCON
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03837730
- Sponsor's protocol ID
- P/2018/353
- Acronym
- CARS
- Status last verified
- Jan 2025
- First submitted
- 8 Feb 2019
- Last updated
- 17 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Activity and Expression of Plasma Arginase in Patients With Severe Sepsis or Septic Shock as Prognostic Value
- ClinicalTrials.gov ID
- NCT03837730
- Acronym / sponsor ID
- CARS / P/2018/353
- Conditions
- Intensive Care Units, Infection, Biomarkers, Sepsis, Septic Shock
- Keywords
- ICU, sepsis, septic shok, arginase, citrulline
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Study start
- 28 May 2019 (actual)
- Primary completion
- 30 Sep 2022 (actual)
- Study completion
- 30 Oct 2022 (actual)
- First posted
- 12 Feb 2019 (actual)
- 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.
Sepsis is an acute pathology defined as an inappropriate response of the host to infection, resulting in the onset of organ failure (Quick SOFA ≥2, or SOFA ≥2). Septic shock is a sepsis associated with an elevation of lactate ≥ 2 mmol / l and an arterial hypotension requiring vasoactive drugs. Several studies highlighted that sepsis is associated with a plasma L-arginine deficiency. This deficiency induces a lower availability of L-arginine for multiple metabolic pathways including those involved in the synthesis of nitric oxide (NO) in the vascular endothelium via NO synthase. NO is the main endogenous vasodilator mediator, a lower synthesis induces a vascular and endothelial dysfunction that can promote the occurrence of an organic dysfunction during sepsis. Decrease in available NO was confirmed in patients with sepsis and appears correlated with severity.
L-arginine deficiency can have multiple origins:
- L-arginine deficiency resulting from a decrease in endogenous production from citrulline synthesized by the enterocytes. Such enterocyte dysfunction has been confirmed in patients with sepsis and is characterized biologically by elevated plasma levels of I-FABP (intestinal fatty acid binding protein - enterocyte-specific protein, cytolysis marker) and lower than that of citrulline (hypocitrullinemia, marker of lower activity).
- L-arginine deficiency may also result from a catabolism increase via arginase activity increased. This ubiquitous enzyme, having 2 isoforms (Arg1 and Arg2), allows the synthesis of urea and ornithine from L-arginine. An increase in arginase activity would decrease the available reserves of L-arginine for NO synthesis.
The objectives of this work is to evaluate, in patients with severe sepsis or septic shock, the prognostic value of the plasma arginase activity and the plasma expression of 2 isoforms Arg1 and Arg2, their kinetics, and the link between activity / expression of arginase and enterocyte dysfunction.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients admitted to the ICU for severe sepsis or septic shock
Key inclusion criteria (6 listed)
- 18 years old or older
- Patient admitted to ICU
- Diagnosis, suspected or confirmed, of severe sepsis or septic shock
- Expected ICU stay of at least 2 days
- Affiliation to a social security system or recipient of a such system
Key exclusion criteria (7 listed)
- Pregnancy
- Chronic intestinal pathology
- Chronic renal failure defined by creatinine clearance <50 ml / min / 1.73m2 (CKD-EPI)
- Severe hepatic insufficiency (Child-Pugh stage C score)
- Legal incapacity or limited legal capacity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
prognostic value of plasma arginase activity and expression at ICU admission in patients with severe sepsis or septic shock
Time frame: 28 days
activity / expression of plasma arginase at ICU admission and 28-day mortality rate from admission to intensive care
2 secondary outcomes
activity / expression kinetic of plasma arginase
Time frame: during the first 7 days of ICU admission
prognostic value of enterocyte damage
Time frame: 28 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 17 Jan 2025.
- Individual participant dataSharing planned: Undecided
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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.
Gaël PITON, MD principal investigator
CHU DE BESANCON
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Intensive Care Units and Infection, run by Centre Hospitalier Universitaire de Besancon at 1 site 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 7 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 17 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
prognostic value of plasma arginase activity and expression at ICU admission in patients with severe sepsis or septic shock (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jan 2025.