Arginine supplementation in severe sepsis: effects on metabolism and microcirculation.|
|- candidate number||1724|
|- NTR Number||NTR423|
|- Date ISRCTN created||27-jan-2006|
|- date ISRCTN requested||18-nov-2005|
|- Date Registered NTR||23-sep-2005|
|- Secondary IDs||MEC 04-136 |
|- Public Title||Arginine supplementation in severe sepsis: effects on metabolism and microcirculation.|
|- Scientific Title||Arginine and nitric oxide (NO) metabolism in sepsis; effects of L-arginine supplementation on whole body and splanchnic metabolism and microcirculation in severely septic patients.|
|- ACRONYM||Arginine-sepsis study.|
|- hypothesis||NO synthesis is compromised during sepsis through lack of L-arginine and may thereby contribute to impaired microcirculation and organ dysfunction. Supplementation of L-arginine in septic patients can replete L-arginine deficiency and will improve microcirculation, vascular permeability, and organ function.|
|- Healt Condition(s) or Problem(s) studied||Sepsis, Septic shock |
|- Inclusion criteria||1. Written informed consent from close relative; |
2. Age > 18 years;
3. Patient meets the general criteria for severe sepsis or septic shock (International published sepsis definitions), diagnosed less than 48 h prior to study inclusion;
4. Patient must be relatively hemodynamically stable, defined as stable blood pressure (variation in mean arterial pressure <15 mm Hg) during 2 h without necessity of increasing the vasopressor dose, inotropic support or rate of fluid administration;
5. Systemic arterial catheter in place with continuous pressure monitoring;
6. Patients in whom the clinician is prepared to provide full life support during the duration of the study.
|- Exclusion criteria||1. Shock due to any cause other than sepsis (e.g. drug reaction or drug overdose, pulmonary embolus, burn injury, severe blood loss etc.);|
2. Prolonged or high dose corticosteroid use;
3. Liver cirrhosis;
4. Chronic pancreatitis;
5. Insulin-dependent diabetes mellitus;
6. Metastases, haematological, malignancies or chemotherapy;
7. Patients on dialysis (CVVH or other);
8. Pre-existent urea cycle disorders or renal failure.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||15-nov-2004|
|- planned closingdate||31-dec-2005|
|- Target number of participants||16|
|- Interventions||1. 3-days intravenous L-arginine infusion;|
2. 3-days intravenous L-alalanine (placebo) infusion.
|- Primary outcome||Microcirculation.|
|- Secondary outcome||1. Arginine metabolism;|
3. Vascular permeability;
4. Organ functions;
5. Disease severity scores.
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||PhD. Y.C. Luiking|
|- CONTACT for SCIENTIFIC QUERIES||MD. PhD. N.E.P. Deutz|
|- Sponsor/Initiator ||Nutrition and Toxicology Research Institute Maastricht (NUTRIM)|
(Source(s) of Monetary or Material Support)
|Novartis Consumer Health - R&D Nutrition|
|- Publications||1. Luiking, Y. C., Poeze, M., Dejong, C. H., Ramsay, G. & Deutz, N. E. (2004) Sepsis: an arginine deficiency state? Crit Care Med 32: 2135-2145.|
2. Bruins, M. J., Soeters, P. B., Lamers, W. H. & Deutz, N. E. (2002) L-arginine supplementation in pigs decreases liver protein turnover and increases hindquarter protein turnover both during and after endotoxemia. Am J Clin Nutr 75: 1031-1044.
3. Bruins, M. J., Luiking, Y. C., Soeters, P. B., Lamers, W. H., Akkermans, L. M. & Deutz, N. E. (2004) Effects of long-term intravenous and intragastric L-arginine intervention on jejunal motility and visceral nitric oxide production in the hyperdynamic compensated endotoxaemic pig. Neurogastroenterol Motil 16: 819-828.
|- Brief summary||Background: |
Sepsis is a severe clinical problem with a high mortality rate, which is caused by a severe inflammatory response to an infection. Nitric oxide (NO), which is produced by the body from the amino acid L-arginine, has an important role in the pathophysiology of the disease. NO has an important role as a vasodilator and therefore is important for vascular perfusion. In a previous study we observed that plasma arginine levels were lowered in sepsis. Moreover, L-arginine supplementation approved to be beneficial in a pig model of sepsis. This has led us to the hypothesis that sepsis is an arginine deficiency state (Luiking, CCM 2004;32:2135-45) and that patients could benefit from L-arginine administration in order to enhance NO production and improve organ perfusion and function.
Aim: The aim of our present study is to study the effects of L-arginine administration on NO production and microcirculation in a placebo controlled, double blind randomized study design.
This information adds to our understanding of the mechanism by which L-arginine supplementation may benefit septic patients. This can be a base for larger trials on arginine supplementation in the future.
|- Main changes (audit trail)|
|- RECORD||23-sep-2005 - 9-okt-2008|
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