Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI TRIAL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Change in HLA-DR Expression on Monocytes 72 Hours After Drug or Placebo Administration in Patient Groups (0g TXA (Placebo); 2g TXA; 4g TXA)."
研究概览
简要总结
The purpose of this study is to evaluate the effects of TXA on the immune system, its pharmacokinetics, as well as safety and efficacy in severely injured trauma patients.
详细描述
Trauma is the leading cause of death in persons younger than 40 years. Hemorrhage is the etiology in 30% of these deaths, and remains the leading cause of potentially preventable mortality (66-80%) on the battlefield. Death secondary to hemorrhagic shock occurs from both surgical bleeding and coagulopathy. Due to the knowledge of increased fibrinolysis promoting a hypocoagulable state in severe trauma, trials have been performed to determine if antifibrinolytics such as tranexamic acid (TXA) could reduce morbidity and mortality by reducing death from hemorrhage. TXA is an antifibrinolytic that inhibits both plasminogen activation and plasmin activity, thus preventing clot break-down rather than promoting new clot formation. Despite the extensive use of TXA in many surgical populations and an increasing use in severe trauma patients, TXA does not have an FDA approved indication for patients with traumatic injuries. The effect of TXA on immune function has not been thoroughly examined, especially in patients with severe traumatic injury. The study of the effects of TXA use on endothelial activation and injury is also important due to the inter-relationship between coagulation and endothelial function. Endothelial injury secondary to local hypoperfusion causes acute traumatic coagulopathy with fibrinolysis. Therefore a thorough and comprehensive evaluation of the effects of TXA on immune, coagulation, and endothelial parameters is important to allow for a better understanding of the mechanisms of action of this agent.
This is a randomized placebo controlled trial to obtain mechanism of action data, pharmacokinetic information, and efficacy and safety data for the use of TXA in severely injured trauma patients. Participants will be randomized into 1 of 3 treatment arms (1:1:1): TXA 2 gram IV bolus, TXA 4 gram IV bolus, or placebo. The study period is from time of enrollment to hospital discharge or transfer. The study intervention will occur only once upon enrollment in the trial. Participants will receive study drug within two hours from their initial injury. Blood samples will be drawn at multiple time points for immune parameters, Pharmacodynamics, and repository samples.
Immune parameter samples will be drawn at at approximately 0, 6, 24 and 72 hours after study drug/placebo administration.
Pharmacokinetic and pharmacodynamic samples will be drawn according to two schedules. Even number sampling times, blood will be drawn at the approximate time points: 0, 20 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, and 12 hr. A patient sampled on odd number sampling times will have samples drawn at the approximate time points: 0, 10 min, 40 min, 1.5 hr, 3 hr, 6 hr, 10 hr and 24 hr.
Repository samples will be drawn at approximate time points: 0, 1, 6, 24, and 72 hours.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Patients with traumatic injury that are ordered to receive at least 1 blood product and/or
- •Patients admitted to the Emergency Department with a traumatic injury and require immediate transfer to the operating room to control the bleeding
- •Able to receive the study drug within 2 hours from estimated time of injury **Please note that in circumstances where the patient initially met inclusion/exclusion criteria (i.e. received blood products in the ED before a full evaluation of their injuries is complete) but is later found to only have a soft tissue involved injury or does not have a traumatic bleeding source), the Investigator may determine that the patient should not be randomized into the trial and the patient should be considered a screen failure
排除标准
- •Patients known to be < 18 years of age
- •Suspected Acute MI or stroke(thromboembolic and/or hemorrhagic) on admission
- •Known inherited coagulation disorders
- •Known history of thromboembolic events (DVT, PE, MI, Stroke)
- •Please note that past medical history of hemorrhagic stroke is permitted, but not current admission with hemorrhagic stroke
- •Known history of seizures and/or seizure after injury/on admission related to this hospitalization
- •Suspected or known pregnancy
- •Known to be lactating
- •Suspected or known prisoners
- •Futile care
- •Known current state of immunosuppression (i.e. on high dose steroids, chemotherapeutics, etc.)
- •Unknown estimated time of injury 12). Patients wearing an "Opt Out" TAMPITI Study bracelet 13). Known presence of subarachnoid hemorrhage.
- •14.) Isolated injuries to hands and/or feet (distal) 15.) Administration of antifibrinolytics pre-hospital and/or during this ED admission prior to enrollment
研究组 & 干预措施
Tranexamic Acid 2 Gram
One time dose IV TXA 2 Grams given over 10 minutes within 2 hours of initial injury
干预措施: Tranexamic Acid (Drug)
Tranexamic Acid 4 Gram
One time dose IV TXA 4 Grams given over 10 minutes within 2 hours of initial injury
干预措施: Tranexamic Acid (Drug)
Placebo
Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury
干预措施: Placebo (Other)
结局指标
主要结局
Change in HLA-DR Expression on Monocytes 72 Hours After Drug or Placebo Administration in Patient Groups (0g TXA (Placebo); 2g TXA; 4g TXA)."
时间窗: Samples Drawn through 72 hours after study initiation
Blood was drawn from patients at baseline (0 h, just before placebo or drug administration) and at 72 hours post placebo or drug administration. Leukocytes in these blood samples were stained with fluroescent antibodies specific for CD45, CD14, and HLA-DR, analyzed by flow cytometry, and the median fluorescen intensity (MFI) of HLA-DR signal was recorded for monocytes (CD45+CD14+). The fold change in HLA-DR expression from prior to placebo/drug administration to 72 h after placebo/drug administration ("0 h : 72 h") was calculated as HLA-DR MFI72hours ÷ HLA-DR CD14 MFI0hours. Non-paramteric one-way ANOVA (Kruskal-Wallis test) was performed between each treatment group at the given time pont, and the p-value reported.
次要结局
- Differences in Cytokine Profiles Between the Three Study Groups(Samples Drawn through 72 hours after study initiation)
- Differences in Leukocyte Function Parameters Between the Three Study Groups(Samples Drawn through 72 hours after study initiation)
- Determine the Incidence of Seizures at 24 Hours in All Three Study Groups.(24 hours following TXA)
- Total Transfusion Volume CL(24 hours)
- Determine the Incidence of Thromboembolic Events (DVT, MI, PE, Stroke) in All Three Study Groups.(Hospital Discharge (average 10 days))
- Q- Intercompartmental Clearance (L/70kg)(24 hours)
- Determine the Incidence of All Adverse Events in All Three Study Groups(Hospital Discharge (average 10 days))
- Platelet Count CL(24 hours)
- Near Infrared Spectroscopy CL(24 hours)
- Creatinine Count CL(24 hours)
- V2- Peripheral Volume (L/70kg)(24 hours)
- V1- Central Volume (L/70kg)(24 hours)
- CL- Clearance of TXA (mL/(Min*70kg))(24 hours)