Citrulline in Severe Sepsis

NCT01474863 | Completed Phase 2 Results

• 1 other identifier: 111435
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Severe Sepsis; Acute Lung Injury

Outcome Measures

Primary Outcomes (1)

• 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)

  day 4

Study Arms (3)

Low Dose Citrulline

ACTIVE COMPARATOR

Low Dose Citrulline

Drug: Low Dose Citrulline

Placebo

PLACEBO COMPARATOR

Placebo IV infusion

Drug: Placebo

High Dose Citrulline

ACTIVE COMPARATOR

High Dose Citrulline

Drug: High Dose Citrulline

Interventions

High Dose Citrulline DRUG

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

High Dose Citrulline

Placebo DRUG

D5W IV fluids at isovolumetric rate (about 15ml/hr)

Placebo

Low Dose Citrulline DRUG

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.

Low Dose Citrulline

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe Sepsis

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Sepsis; Acute Lung Injury

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Injury; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Todd Rice, MD
• Organization: Vanderbilt University Medical Center

todd.rice@vanderbilt.edu

6153223412

Study Officials

• Todd Rice, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: November 11, 2011
• First Posted: November 18, 2011
• Study Start: August 1, 2012
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: June 5, 2017
• Results First Posted: June 5, 2017

Record last verified: 2017-06

Locations

US (1)