Rapid Administration of Carnitine in sEpsis

NCT01665092 | Completed Phase 2 Results DMC

• 1 other identifier: GM103799
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 14

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.

Conditions

Septic Shock

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

Control

PLACEBO COMPARATOR

Normal saline

Drug: placebo

Carnitine Low

EXPERIMENTAL

Levo-Carnitine 6g

Drug: Levo-Carnitine

Carnitine Medium

EXPERIMENTAL

Levo-Carnitine 12 g

Drug: Levo-Carnitine

Carnitine High

EXPERIMENTAL

Levo-Carnitine 18 g

Drug: Levo-Carnitine

Interventions

Levo-Carnitine DRUG

Carnitine High; Carnitine Low; Carnitine Medium

placebo DRUG

Control

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Mississippi Medical Center: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (14)

University of Alabama Birmingham

Birmingham, Alabama, United States

Location

Univeristy of California Davis

Sacramento, California, United States

Location

Christiana Care Health Services

Wilmington, Delaware, United States

Location

University of Florida

Jacksonville, Florida, United States

Location

Northwestern University

Chicago, Illinois, United States

Location

Indiana University

Indianapolis, Indiana, United States

Location

BIDMC

Boston, Massachusetts, United States

Location

BWH

Boston, Massachusetts, United States

Location

MGH

Boston, Massachusetts, United States

Location

St. Vincent Hospital

Worcester, Massachusetts, United States

Location

Wayne State University

Detroit, Michigan, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 29316, United States

Location

Cooper University Hospital

Camden, New Jersey, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, United States

Location

Related Publications (1)

• 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.

  PMID: 30646314 DERIVED

MeSH Terms

Conditions

Shock, Septic

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Results Point of Contact

• Title: Alan Jones
• Organization: Univeristy of Mississippi Medical Center

aejones@umc.edu

601-384-5586

Study Officials

• Alan Jones, MD

  University of Mississippi Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Emergency Medicine

Study Record Dates

• First Submitted: August 11, 2012
• First Posted: August 15, 2012
• Study Start: January 1, 2013
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2019
• Last Updated: June 4, 2019
• Results First Posted: June 4, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)