Citrulline in Severe Sepsis
Primary Purpose
Severe Sepsis, Acute Lung Injury
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
High Dose Citrulline
Placebo
Low Dose Citrulline
Sponsored by
About this trial
This is an interventional prevention trial for Severe Sepsis
Eligibility Criteria
Inclusion Criteria:
- Severe Sepsis
Exclusion Criteria:
- No Consent
- Malignant or other irreversible condition
- Moribund and not expected to survive 48 hours
- End Stage Liver Disease
- Enrolled in another IND study
- Pregnant or breast feeding female
- Age<13 years old
- Allergy to citrulline or arginine
Sites / Locations
- Vanderbilt University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Placebo Comparator
Active Comparator
Arm Label
Low Dose Citrulline
Placebo
High Dose Citrulline
Arm Description
Low Dose Citrulline
Placebo IV infusion
High Dose Citrulline
Outcomes
Primary Outcome Measures
Vasopressor Dependency Index
Worst Value of Index measuring blood pressure hourly through study infusion (day 4). Vasopressor index is mean arterial blood pressure divided by catecholamine index (the catecholamine index is a dimensionless variable calculated as (dopamine dose × 1) + (dobutamine dose × 1) + (adrenaline dose × 10) + (noradrenaline × 100) + (phenylephrine dose × 100), where all doses are expressed in ug/kg/min). (Higher is better)
Secondary Outcome Measures
Full Information
NCT ID
NCT01474863
First Posted
November 11, 2011
Last Updated
June 2, 2017
Sponsor
Vanderbilt University
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT01474863
Brief Title
Citrulline in Severe Sepsis
Official Title
Prospective, Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Intravenous Citrulline to Prevent or Mitigate Acute Lung Injury in Patients With Severe Sepsis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University
Collaborators
National Institutes of Health (NIH)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a randomized, double-blind, placebo-controlled, phase 2 study to evaluate biochemical, clinical, and safety effects of 2 doses of intravenous L-citrulline compared to placebo in patients with severe sepsis at risk for or with acute lung injury. The hypothesis is that intravenous L-citrulline will decreased the development or progression of acute lung injury in patients with severe sepsis compared to placebo.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis, Acute Lung Injury
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
72 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low Dose Citrulline
Arm Type
Active Comparator
Arm Description
Low Dose Citrulline
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo IV infusion
Arm Title
High Dose Citrulline
Arm Type
Active Comparator
Arm Description
High Dose Citrulline
Intervention Type
Drug
Intervention Name(s)
High Dose Citrulline
Intervention Description
Initial intravenous bolus of 20mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 9mg/kg (max 700mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
D5W IV fluids at isovolumetric rate (about 15ml/hr)
Intervention Type
Drug
Intervention Name(s)
Low Dose Citrulline
Intervention Description
Initial intravenous bolus of 10mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 4.5mg/kg (max 350mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days.
Primary Outcome Measure Information:
Title
Vasopressor Dependency Index
Description
Worst Value of Index measuring blood pressure hourly through study infusion (day 4). Vasopressor index is mean arterial blood pressure divided by catecholamine index (the catecholamine index is a dimensionless variable calculated as (dopamine dose × 1) + (dobutamine dose × 1) + (adrenaline dose × 10) + (noradrenaline × 100) + (phenylephrine dose × 100), where all doses are expressed in ug/kg/min). (Higher is better)
Time Frame
day 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Severe Sepsis
Exclusion Criteria:
No Consent
Malignant or other irreversible condition
Moribund and not expected to survive 48 hours
End Stage Liver Disease
Enrolled in another IND study
Pregnant or breast feeding female
Age<13 years old
Allergy to citrulline or arginine
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Todd Rice, MD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
12. IPD Sharing Statement
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Citrulline in Severe Sepsis
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