Rapid Administration of Carnitine in sEpsis (RACE)
Primary Purpose
Septic Shock
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Levo-Carnitine
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Septic Shock
Eligibility Criteria
Inclusion Criteria:
- 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)
- Any two of four criteria of systemic inflammatory response as defined by the 2001 ACCP/SCCM Consensus Conference Committee;
- Recognition of septic shock and initiation of quantitative resuscitation within 24 hours of enrollment;
- 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;
- Cumulative sequential organ failure assessment (SOFA) score of ≥ 6;
- Blood lactate level of >2.0 mMol/L.
Exclusion Criteria:
- Age <18 years;
- Pregnancy or breastfeeding;
- Any primary diagnosis other than sepsis;
- Established Do Not Resuscitate status or advanced directives restricting aggressive care or treating physician deems aggressive care unsuitable;
- Any history of seizures or a known seizure disorder;
- Any known inborn error of metabolism;
- Anticipated requirement for surgery that would interfere with the 12 hour infusion time;
- Active participation in another interventional study;
- Cardiopulmonary resuscitation (chest compression or defibrillation) prior to enrollment;
- Known systemic allergy to L-carnitine.
- 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).
- Active Treatment with Coumadin
Sites / Locations
- University of Alabama Birmingham
- Univeristy of California Davis
- Christiana Care Health Services
- University of Florida
- Northwestern University
- Indiana University
- BIDMC
- BWH
- MGH
- St. Vincent Hospital
- Wayne State University
- University of Mississippi Medical Center
- Cooper University Hospital
- Carolinas Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Control
Carnitine Low
Carnitine Medium
Carnitine High
Arm Description
Normal saline
Levo-Carnitine 6g
Levo-Carnitine 12 g
Levo-Carnitine 18 g
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01665092
First Posted
August 11, 2012
Last Updated
May 16, 2019
Sponsor
University of Mississippi Medical Center
Collaborators
National Institute of General Medical Sciences (NIGMS)
1. Study Identification
Unique Protocol Identification Number
NCT01665092
Brief Title
Rapid Administration of Carnitine in sEpsis
Acronym
RACE
Official Title
Phase 2 Study of Levo-Carnitine for Vasopressor Dependent Septic Shock
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
March 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Mississippi Medical Center
Collaborators
National Institute of General Medical Sciences (NIGMS)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
250 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Normal saline
Arm Title
Carnitine Low
Arm Type
Experimental
Arm Description
Levo-Carnitine 6g
Arm Title
Carnitine Medium
Arm Type
Experimental
Arm Description
Levo-Carnitine 12 g
Arm Title
Carnitine High
Arm Type
Experimental
Arm Description
Levo-Carnitine 18 g
Intervention Type
Drug
Intervention Name(s)
Levo-Carnitine
Intervention Type
Drug
Intervention Name(s)
placebo
Primary Outcome Measure Information:
Title
Delta SOFA Score
Description
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.
Time Frame
48 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
Any two of four criteria of systemic inflammatory response as defined by the 2001 ACCP/SCCM Consensus Conference Committee;
Recognition of septic shock and initiation of quantitative resuscitation within 24 hours of enrollment;
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;
Cumulative sequential organ failure assessment (SOFA) score of ≥ 6;
Blood lactate level of >2.0 mMol/L.
Exclusion Criteria:
Age <18 years;
Pregnancy or breastfeeding;
Any primary diagnosis other than sepsis;
Established Do Not Resuscitate status or advanced directives restricting aggressive care or treating physician deems aggressive care unsuitable;
Any history of seizures or a known seizure disorder;
Any known inborn error of metabolism;
Anticipated requirement for surgery that would interfere with the 12 hour infusion time;
Active participation in another interventional study;
Cardiopulmonary resuscitation (chest compression or defibrillation) prior to enrollment;
Known systemic allergy to L-carnitine.
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).
Active Treatment with Coumadin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan Jones, MD
Organizational Affiliation
University of Mississippi Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama Birmingham
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Univeristy of California Davis
City
Sacramento
State/Province
California
Country
United States
Facility Name
Christiana Care Health Services
City
Wilmington
State/Province
Delaware
Country
United States
Facility Name
University of Florida
City
Jacksonville
State/Province
Florida
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
Country
United States
Facility Name
BIDMC
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
BWH
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
MGH
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
St. Vincent Hospital
City
Worcester
State/Province
Massachusetts
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
29316
Country
United States
Facility Name
Cooper University Hospital
City
Camden
State/Province
New Jersey
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30646314
Citation
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.
Results Reference
derived
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Rapid Administration of Carnitine in sEpsis
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