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Phase 2 N=250 Randomized Quadruple-blind Treatment

Rapid Administration of Carnitine in sEpsis

Septic Shock

Enrolled (actual)
250
Serious AEs
0.0%
Results posted
Jun 2019
Primary outcome: Primary: Delta SOFA Score — -1.8; -0.34; -1.68; -2.15 units on a scale

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Levo-Carnitine (Drug); placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
University of Mississippi Medical Center
Primary completion
Mar 2018

Outcome Measures

OutcomeResultp-value
PRIMARY
Delta SOFA Score
-1.8; -0.34; -1.68; -2.15

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

  • 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01665092). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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