Rapid Administration of Carnitine in sEpsis (RACE)

University of Mississippi

Status and phase: Completed; Phase 2

Conditions: Septic Shock

Treatments: Drug: placebo; Drug: Levo-Carnitine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01665092

GM103799

Details and patient eligibility

About

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.

Enrollment: 250 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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250 participants in 4 patient groups, including a placebo group

Control

Placebo Comparator group

Description:

Normal saline

Treatment:

Drug: placebo

Carnitine Low

Experimental group

Description:

Levo-Carnitine 6g

Treatment:

Drug: Levo-Carnitine

Carnitine Medium

Experimental group

Description:

Levo-Carnitine 12 g

Treatment:

Drug: Levo-Carnitine

Carnitine High

Experimental group

Description:

Levo-Carnitine 18 g

Treatment:

Drug: Levo-Carnitine