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Dose-response Study of Arginine Supplementation in Severe Sepsis

This study has been completed.
Sponsor:
Collaborator:
Novartis Medical Nutrition
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01775020
First received: January 21, 2013
Last updated: January 28, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Sepsis
Septic Shock
 Dietary Supplement: L-arginine
 Phase 0

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Arginine and Nitric Oxide (NO) Metabolism in Sepsis; Dose-response Study on the Effect of L-arginine Supplementation on NO Metabolism and Gastric Perfusion in Severe Septic Patients.

Resource links provided by NLM:

MedlinePlus related topics: Sepsis Shock
U.S. FDA Resources

Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • Nitric oxide synthesis [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    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:
  • hemodynamics [ Time Frame: 8 hours ] [ Designated as safety issue: Yes ]
    Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), cardiac output (CO), cardiac index (CI), heart rate (HR)

  • blood parameters [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    Blood gasses, electrolytes, glucose, insulin, amino acids, whole body protein and arginine metabolism

  • gastric perfusion [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    Regional (gastric) CO2 production measured with tonometry (PrCO2)


Enrollment: 8
Study Start Date: October 2003
Study Completion Date: May 2012
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: L-arginine
L-arginine
 Dietary Supplement: L-arginine
Other Name: L-arginine-HCl

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01775020

Sponsors and Collaborators
Maastricht University Medical Center
Novartis Medical Nutrition
Investigators
Principal Investigator: Nicolaas E Deutz, MD PhD
  More Information

Publications:

Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01775020     History of Changes
Other Study ID Numbers: MEC03-139.5
Study First Received: January 21, 2013
Last Updated: January 28, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Sepsis
Toxemia
Shock
Shock, Septic
 Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on June 18, 2013