Exogenous Sodium Lactate Infusion in Traumatic Brain Injury (ELI-TBI)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 264
- 主要终点
- mortality
研究概览
简要总结
This is a safety phase 2 clinical trial of intravenous infusion of sodium lactate in patients with severe TBI. This study is intended for patients in the acute setting in an intensive care unit at centers that have been selected to participate in this trial. This is a proof of safety study and biomarker response study.
详细描述
Traumatic brain injury (TBI) consists of a primary localized insult to the brain followed by prolonged global disruption of brain metabolism, thus creating risk for secondary brain damage from energy deficiency. To date, there is no specific metabolic treatment to improve outcome after TBI. This study is designed to determine if providing a unique chemical fuel in the form sodium lactate will improve the brain's metabolism and prevent ongoing damage. The investigators will seek to find the highest dose of sodium lactate that is tolerated and then to determine if administering this dose for 24 hours improves brain metabolism and survival. We will collect blood and brain MRI images to test if the intervention helps brain metabolism and brain structure. The study will be a randomized trial so that we have a comparison group against which to best evaluate safety. Ten medical centers that are very experienced with traumatic brain injury will participate in the study and will be supervised by a data safety monitoring board. This is a pilot study that will ultimately inform the design of a large scale clinical trial of sodium lactate in the near future.
RATIONALE TBI has no definitive drug treatment, and multiple trials have failed. We propose a pilot safety study of a metabolic treatment for TBI using exogenous sodium lactate (ELI) infusion to enhance brain oxidative metabolism as a medical treatment for TBI.
STUDY DESIGN This is a multicenter phase 2 study. The phase 2a study will identify the maximum tolerated dose of ELI using the continual reassessment dose escalation design with three dose tiers and will be followed by a phase 2b, randomized, placebo-controlled comparison of the ELI at maximum tolerated dose (MTD) for 24 hours vs normal saline infusion. The time to enrollment and start of study infusion will be 24 hours after onset of TBI.
PRIMARY OBJECTIVE The primary objective of part 1, the dose finding study is to determine the maximum tolerated dose (MTD) associated with a prespecified probability of dose limiting toxicity (DLT). The DLT is defined as the occurrence within 7 days of ELI of any one of three adverse events: AKI, arrythmia (atrial or ventricular tachycardia that causes hypotension), or ARDS (mild or greater).
The primary objective of the part 2 of the study, the randomized trial of MTD ELI for 24 hours vs saline is 30 day mortality.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Participant is not awake and is not told which arm they were randomized to Assessor is blinded to randomization allocation
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •GCS at enrollment 3-8
- •Male or female aged 18-80 at admission
- •acute positive CT findings
- •ability for subject to comply with the requirements of the study
- •written informed consent obtained from subject or subject's legal representative.
排除标准
- •Penetrating TBI
- •Polytrauma leading to instability of systemic: hemodynamics, acidosis, or severe acute lung injury during the inclusion period
- •History of neurological disease, including Parkinson's, Huntington's, Alzheimer's, etc.
- •History of diabetes mellitus
- •Serum sodium ≥ 148 mM
- •Metabolic acidosis pH <7.34
- •Coagulopathy INR > 1.3, platelets < 100,000, or hematocrit < 28 mg/dl
- •Renal insufficiency with GFR < 60% of expected or Cr > 1.3;
- •AST or ALT > 1.5x upper limit of normal; Severe liver trauma;
- •baseline serum lactate > 2 mM
- •Hypotension SBP < 90 refractory to vasopressors
- •Known mitochondrial genetic disorder
- •Pregnancy
- •Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
- •Member of a protected population; simultaneous participation in another randomized trial
研究组 & 干预措施
intervention
sodium lactate
干预措施: Sodium Lactate (Drug)
placebo
sodium cbloride infusion
干预措施: placebo (Drug)
结局指标
主要结局
mortality
时间窗: 30 days
Mortality
Dose limiting toxicity
时间窗: 7 days
panel of serious adverse events
次要结局
未报告次要终点
研究者
Paul Vespa, MD
Professor and Assistant Dean
University of California, Los Angeles