Rapid Administration of Carnitine in sEpsis (RACE)

Phase 2 Study of Levo-Carnitine for Vasopressor Dependent Septic Shock

Prior work has shown that exogenous L-carnitine administration enhances glucose and lactate oxidation, attenuates fatty acid toxicity, and improves endothelial-smooth muscle coupling and cardiac mechanical efficiency. The overall goal of this proposal is to investigate L-carnitine as a novel adjunctive treatment of septic shock. In this study the investigators will test our primary hypothesis: Early adjunctive L-carnitine administration in vasopressor dependent septic shock will significantly reduce cumulative organ failure at 48 hours with an associated decrease in 28-day mortality suggesting the need for further phase III study. To accomplish this the investigators will conduct a phase II, double blinded, placebo controlled, adaptive randomized trial of 250 eligible patients with vasopressor-dependent septic shock. Study subjects will be assigned to one of four arms: low (6g), medium (12g) or high (18g) dose intravenous L-carnitine or placebo for 12 hours as a part of early resuscitative care.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: placebo; Drug: Levo-Carnitine

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • University of Alabama Birmingham
  • California
    • Sacramento, California, United States
      • Univeristy of California Davis
  • Delaware
    • Wilmington, Delaware, United States
      • Christiana Care Health Services
  • Florida
    • Jacksonville, Florida, United States
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States
      • Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States
      • MGH
    • Boston, Massachusetts, United States
      • BIDMC
    • Boston, Massachusetts, United States
      • BWH
    • Worcester, Massachusetts, United States
      • St. Vincent Hospital
  • Michigan
    • Detroit, Michigan, United States
      • Wayne State University
  • Mississippi
    • Jackson, Mississippi, United States, 29316
      • University of Mississippi Medical Center
  • New Jersey
    • Camden, New Jersey, United States
      • Cooper University Hospital
  • North Carolina
    • Charlotte, North Carolina, United States
      • Carolinas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Suspected or confirmed infection (examples include but are not limited to: white cells in a normally sterile body fluid; perforated viscus; radiographic evidence of pneumonia in clinical symptoms; a syndrome associated with a high risk of infection e.g. cellulitis, cutaneous abscess, ascending cholangitis, toxic shock syndrome, fever of unknown origin with high suspicion of infectious etiology)
2. Any two of four criteria of systemic inflammatory response as defined by the 2001 ACCP/SCCM Consensus Conference Committee;
3. Recognition of septic shock and initiation of quantitative resuscitation within 24 hours of enrollment;
4. Requirement of high dose vasopressors for ≥4 hours to treat shock: Norepinephrine > 0.05mcg/kg/min; dopamine >10mcg/kg/min; Phenylephrine >0.4 mcg/kg/min; epinephrine > 0.05 mcg/kg/min;
5. Cumulative sequential organ failure assessment (SOFA) score of ≥ 6;
6. Blood lactate level of >2.0 mMol/L.

Exclusion Criteria:

1. Age <18 years;
2. Pregnancy or breastfeeding;
3. Any primary diagnosis other than sepsis;
4. Established Do Not Resuscitate status or advanced directives restricting aggressive care or treating physician deems aggressive care unsuitable;
5. Any history of seizures or a known seizure disorder;
6. Any known inborn error of metabolism;
7. Anticipated requirement for surgery that would interfere with the 12 hour infusion time;
8. Active participation in another interventional study;
9. Cardiopulmonary resuscitation (chest compression or defibrillation) prior to enrollment;
10. Known systemic allergy to L-carnitine.
11. Severe immunocompromised state (e.g. subject has neutropenia [receiving cytotoxic chemotherapy with absolute neutrophil count <500/uL or expected to decline to < 500 uL within the next three days).
12. Active Treatment with Coumadin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; Normal saline	Drug: placebo
Experimental: Carnitine Low; Levo-Carnitine 6g	Drug: Levo-Carnitine
Experimental: Carnitine Medium; Levo-Carnitine 12 g	Drug: Levo-Carnitine
Experimental: Carnitine High; Levo-Carnitine 18 g	Drug: Levo-Carnitine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta SOFA Score	Sequential Organ Failure Assessment Score (0-24 range). Delta SOFA is calculated as (SOFA Score at 48 hours post enrollment minus SOFA Score at enrollment). A negative value indicates improvement in the score.	48 hours

Collaborators and Investigators

• Sponsor: University of Mississippi Medical Center
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Alan Jones, MD, University of Mississippi Medical Center

Publications and helpful links

General Publications

• Jones AE, Puskarich MA, Shapiro NI, Guirgis FW, Runyon M, Adams JY, Sherwin R, Arnold R, Roberts BW, Kurz MC, Wang HE, Kline JA, Courtney DM, Trzeciak S, Sterling SA, Nandi U, Patki D, Viele K. Effect of Levocarnitine vs Placebo as an Adjunctive Treatment for Septic Shock: The Rapid Administration of Carnitine in Sepsis (RACE) Randomized Clinical Trial. JAMA Netw Open. 2018 Dec 7;1(8):e186076. doi: 10.1001/jamanetworkopen.2018.6076.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: August 11, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimate): August 15, 2012

Study Record Updates

• Last Update Posted (Actual): June 4, 2019
• Last Update Submitted That Met QC Criteria: May 16, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Shock, Septic
• Other Study ID Numbers: GM103799

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No