Dose-response Study of Arginine Supplementation in Severe Sepsis

NCT ID: NCT01775020

Last Updated: 2013-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-31
• Study Completion Date: 2012-05-31

Brief Summary

Pilot data in patients and data from pig studies indicate that arginine-NO metabolism is impaired in sepsis with changes in splanchnic metabolism and function, and reduced survival at low nitrate levels. Prolonged intravenous supplementation of L-arginine proved effective in pigs for increasing NO production, restoring gut function, and inhibiting an increase in pulmonary arterial pressure, without any deleterious systemic side effects. Prolonged intravenous L-arginine supplementation could therefore be useful in septic ICU patients.

Conditions

Sepsis; Septic Shock

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

L-arginine

L-arginine

Group Type: EXPERIMENTAL

L-arginine

Intervention Type: DIETARY_SUPPLEMENT

Interventions

L-arginine

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

L-arginine-HCl

Eligibility Criteria

Inclusion Criteria

• Written informed consent from close relative
• Age > 18 years
• Patient meets the general criteria for severe sepsis or septic shock, diagnosed less than 48 h prior to study inclusion (see appendix A; in Dutch).
• 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.
• Systemic and pulmonary arterial catheters in place with continuous pressure monitoring.
• Patients in whom the clinician is prepared to provide full life support during the duration of the study, including a life expectance of > 24 h.

Exclusion Criteria

• Shock due to any cause other than sepsis (e.g. drug reaction or drug overdose, pulmonary embolus, burn injury etc.)
• Corticosteroid use (prolonged intake of > 1mg/kg daily or intake of > 70 mg/day for 7 consecutive days within 1 month preceding the study)
• Liver cirrhosis
• Chronic pancreatitis
• Diabetes mellitus type I
• Metastases, haematological malignancies or chemotherapy
• Patients on dialysis (CVVH or other)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Medical Nutrition

UNKNOWN

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicolaas E Deutz, MD PhD

Role: PRINCIPAL_INVESTIGATOR

References

Luiking YC, Poeze M, Ramsay G, Deutz NE. Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am J Clin Nutr. 2009 Jan;89(1):142-52. doi: 10.3945/ajcn.2007.25765. Epub 2008 Dec 3.

Reference Type: BACKGROUND

PMID: 19056593 (View on PubMed)

Poeze M, Bruins MJ, Kessels F, Luiking YC, Lamers WH, Deutz NE. Effects of L-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia. Am J Clin Nutr. 2011 Jun;93(6):1237-47. doi: 10.3945/ajcn.110.007237. Epub 2011 Apr 20.

Reference Type: BACKGROUND

PMID: 21508091 (View on PubMed)

Other Identifiers

MEC03-139.5

Identifier Type: -

Identifier Source: org_study_id