Rapid Administration of Carnitine in sEpsis

Phase 2

Completed

• Conditions: Septic Shock
• Interventions: Drug: placebo; Drug: Levo-Carnitine

• Registration Number: NCT01665092
• Lead Sponsor: University of Mississippi Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-08-11
• Study First Submitted QC: 2012-08-14
• Study First Posted: 2012-08-15
• Study Start: 2013-01
• Primary Completion: 2018-03
• Study Completion: 2019-03
• Results First Submitted: 2019-04-23
• Status Verified: 2019-05
• Results First Submitted QC: 2019-05-16
• Last Update Submitted: 2019-05-16
• Results First Posted: 2019-06-04
• Last Update Posted: 2019-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 250

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	placebo	Normal saline
Carnitine Low	Levo-Carnitine	Levo-Carnitine 6g
Carnitine Medium	Levo-Carnitine	Levo-Carnitine 12 g
Carnitine High	Levo-Carnitine	Levo-Carnitine 18 g

Primary Outcome Measures

Name	Time	Method
Delta SOFA Score	48 hours	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.

Trial Locations

Locations (14)

BWH; 🇺🇸 Boston, Massachusetts, United States

Christiana Care Health Services; 🇺🇸 Wilmington, Delaware, United States

Cooper University Hospital; 🇺🇸 Camden, New Jersey, United States

University of Florida; 🇺🇸 Jacksonville, Florida, United States

St. Vincent Hospital; 🇺🇸 Worcester, Massachusetts, United States

Univeristy of California Davis; 🇺🇸 Sacramento, California, United States

BIDMC; 🇺🇸 Boston, Massachusetts, United States

Wayne State University; 🇺🇸 Detroit, Michigan, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

MGH; 🇺🇸 Boston, Massachusetts, United States

University of Alabama Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Carolinas Medical Center; 🇺🇸 Charlotte, North Carolina, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States