Phase 2 Study of Levo-Carnitine for Vasopressor Dependent Septic Shock
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 250
- 试验地点
- 14
- 主要终点
- Delta SOFA Score
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Control
Normal saline
干预措施: placebo (Drug)
Carnitine Low
Levo-Carnitine 6g
干预措施: Levo-Carnitine (Drug)
Carnitine Medium
Levo-Carnitine 12 g
干预措施: Levo-Carnitine (Drug)
Carnitine High
Levo-Carnitine 18 g
干预措施: Levo-Carnitine (Drug)
结局指标
主要结局
Delta SOFA Score
时间窗: 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.
次要结局
未报告次要终点
研究者
Alan Jones
Professor of Emergency Medicine
University of Mississippi Medical Center