Rapid Administration of Carnitine in sEpsis
Condition: Septic Shock
MeSH terms: Shock, Septic
Intervention: Levo-Carnitine; placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 250.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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