Effect of Citrulline on the Clinical and Biochemical Evolution of Patients With Sepsis.

Study Overview
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Brief Summary
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Triple blind placebo-controlled study to determine if administering citrulline in patients with sepsis and severe sepsis slows progression to multiple organ failure and death, measuring biomarkers of endothelial dysfunction. Patients are divided into placebo or citrulline and followed up for 1 month.

Detailed Description
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Consecutive patients with sepsis are being recited from intensive care unite of IMSS at the CMN Siglo XXI and CMN La Raza over the period of november 2015 through june 2016. After signing an informed consent they will be randomized into 80 for intervention arm and 80 for the placebo arm. All patients will receive usual medical treatment; and during seven days citurlline arm subjects will receive supplementation with oral or nasogastric citrulline (10 g/day), while other group patients will receive during seven days oral or nasogastric placebo (10 g/day) with no visible difference between these. Microalbuminuria and interleukines 1, 6, and 10 will be measured at randomization and at day 7. All subjects will be followed for 28 days, and after the follow-up period results will be analyzed to determine de efficacy and safety of citrulline, primary outcome are the incidence of multiple organic failure and death, also microalbuminuria levels 1,6,10-interleukines. We will use Student-t and Chi2 for statistical analysis.

Official Title
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Controlled Randomized Multi-centric Clinical Trial on the Effect of Citrulline on the Clinical and Biochemical Evolution of Patients With Sepsis.

Conditions
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Sepsis

Intervention / Treatment
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* Dietary Supplement: Citrulline malate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sepsis Severe sepsis Diagnosis of sepsis in the first 36 hours of hospitalization. Informed Consent Intestinal tract intact Exclusion Criteria: Terminal cancer Acute and chronic liver diseases Chronic renal failure. Acute renal failure AKIN III. Pregnant and postpartum women Dying patients. Patients with cardiac arrest. Active gastrointestinal bleeding. Steroids or immunosuppressants. Enrolled in another study intervention. Citrulline allergy.

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: Intervention<br>Oral or nasogastric administration of 10 g citrulline malate daily. Blood and urine samples to determine biomarkers of endothelial damage (IL 6, IL 10 , nitric oxide and microalbuminuria), with a second sampling after 7 days of intervention. Disease severity will be measure with various scales, including APACHE II, SOFA | Dietary Supplement: Citrulline malate<br>* Active comparator: 10 g/day citrulline malate during 7 days<br>* Other names: Citrulline;|
| Placebo Comparator: Placebo<br>10 g of maltodextrin will be substituted for the citrulline. Blood and urine samples to determine biomarkers of endothelial damage (IL 6, IL 10 , nitric oxide and microalbuminuria), with a second sampling after 7 days of intervention. Disease severity will be measure with various scales, including APACHE II, SOFA | Dietary Supplement: Citrulline malate<br>* Active comparator: 10 g/day citrulline malate during 7 days<br>* Other names: Citrulline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple organ failure | Progression to multiple organ failure ending in death | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, citrulline, endothelial, toxemia, endothelial determination of progression, with vs without citrulline