Dose-response Study of Arginine Supplementation in Severe Sepsis

Early Phase 1

Completed

• Conditions: Sepsis; Septic Shock
• Interventions: Dietary Supplement: L-arginine

• Registration Number: NCT01775020
• Lead Sponsor: Maastricht University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-10
• Primary Completion: 2004-05
• Study Completion: 2012-05
• Status Verified: 2013-01
• Study First Submitted: 2013-01-21
• Study First Submitted QC: 2013-01-21
• Study First Posted: 2013-01-24
• Last Update Submitted: 2013-01-28
• Last Update Posted: 2013-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
L-arginine	L-arginine	L-arginine

Primary Outcome Measures

Name	Time	Method
Nitric oxide synthesis	8 hours	Nitric oxide synthesis at step-wise increasing doses of L-arginine infusion. Following a 2h baseline measurements, 3 stepwise increasing arginine doses each provided for 2h will be tested for the effect on NO synthesis.

Secondary Outcome Measures

Name	Time	Method
hemodynamics	8 hours	Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), cardiac output (CO), cardiac index (CI), heart rate (HR)
blood parameters	8 hours	Blood gasses, electrolytes, glucose, insulin, amino acids, whole body protein and arginine metabolism
gastric perfusion	8 hours	Regional (gastric) CO2 production measured with tonometry (PrCO2)