STAT (STatins and Aspirin in Trauma) Trial: A Phase II, Pragmatic, Prospective, Randomized, Double-blind, Adaptive Clinical Trial Examining the Efficacy of Statins and Aspirin in the Reduction of Acute Lung Injury and Venous Thromboembolism in Patients With Fibrinolysis Shutdown
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Incidence of VTE
研究概览
简要总结
This is a phase II, pragmatic, prospective, randomized, double-blind, adaptive clinical trial examining the efficacy of statins and aspirin in the reduction of acute lung injury and venous thromboembolism in patients with fibrinolysis shutdown.
详细描述
This protocol describes a Phase II, pragmatic, prospective, randomized, double-blind, adaptive clinical trial comparing combination rosuvastatin and aspirin therapy to placebo. Currently, there is no treatment for fibrinolysis shutdown or effective measures to prevent macro- and micro-thrombosis post-injury, thus, placebos are acceptable as the control group. Treatment for both groups would otherwise be by standard of care, which includes pharmacologic thromboembolism prophylaxis. The safety of concomitant use of VTE pharmacological prophylaxis with statins and aspirin is well documented in cardiac surgery patients.
Eligible adult patients with anticipated ICU admission will be screened for eligibility in the STAT trial (see inclusion/exclusion criteria) based on history, physical exam and clinical data obtained during their initial treatment. If deemed eligible for enrollment in the STAT trial, the patient, their legally authorized representative (LAR), or their proxy decision-maker will be contacted by our on-site professional research assistants (PRAs) for consent to enroll in the study. Only patients for whom consent is obtained within 24 hours post-injury will be eligible for randomization into the treatment phase of the study.
Upon consent, blood samples will be obtained immediately after consent at 6, 12, 24, 48, 72, 120 and 168 hours after injury. Traditional and tPA-Challenge TEG will be performed on these samples to evaluate the development of the three fibrinolysis phenotypes. Upon receiving an order for prophylactic anticoagulation, the DHMC pharmacy will randomize the patient to the control or intervention arms of the study. Randomization will occur using a computer-generated block (groups of 20 patients) random number sequence in sealed, opaque envelopes maintained at the DHMC pharmacy. Patients assigned to the intervention arm will receive the standard of care anticoagulation plus the combination experimental drugs (20mg of rosuvastatin daily and 325mg of aspirin) daily either orally or crushed via feeding tube. These doses are consistent with those currently recommended in the postoperative period following cardiac surgery. Patients assigned to the control group will receive identical-looking placebos at the same time points as the experimental group either orally or crushed via feeding tube.
Healthcare providers, PRAs and patients will be blinded to study allocation standard of care anticoagulation plus the combination placebos (produced to look and group assignment (double-blind design).
The DHMC pharmacist will be aware of the patient's treatment arm so that rapid un-blinding will be possible in the event of an adverse event possibly related to a study medication. The blood samples will be used to monitor for the type of fibrinolysis, the function of the biochemical mediators of coagulation and potential side effects of these medications, as explained in more detail below.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •all adult trauma patients requiring admission to the surgical intensive care unit (SICU) and expected hospital stay for at least 3 days. Outside hospital transfer patients that require SICU admission less than 24 hours after their injury are also eligible for enrollment.
- •Exclusion criteria for prophylactic anticoagulation and for the study are:
- •Known inherited bleeding disorder or coagulopathy
- •Known contraindication to pharmacologic anticoagulation
- •Spinal column fracture with epidural hematoma
- •Head trauma/central nervous system injury
- •Severe TBI; defined as AIS Head >3
- •Intracranial hemorrhage; subdural or epidural hematoma
- •Neurosurgery service objection; neurosurgical contra-indications will be documented
- •Ongoing hemorrhage requiring blood product transfusion
- •Thrombocytopenia (platelet count < 50,000)
- •Non-operatively managed liver or spleen injuries Grade III or above
- •Known chronic kidney disease (GFR < 15ml/min)
- •Rising creatinine (Cr > 1.5x baseline) at the time of enrollment
- •Inclusion in any other clinical trial
- •Documented previous ischemic strokes
- •In addition, the following exclusion criteria apply:
- •Receiving statin or aspirin therapy pre-injury, as potentially being assigned for Control would increase patient's risks
- •Known allergy or other contraindication to statins or aspirin
- •Pregnant patients
- •Prisoners, as their ability to freely consent is impaired
- •Inability to obtain consent from patient or proxy prior to 48 hours post-injury
- •VTE event (DVT or PE) diagnosed during current hospitalization prior to obtaining informed consent
排除标准
- 未提供
研究组 & 干预措施
Experimental
Administration of 325mg Aspirin and 20mg of Rosuvastatin mixture in a single capsule daily either orally or via a feeding tube for the duration of the patient's stay in the ICU.
干预措施: Aspirin and Rosuvastatin (Drug)
Control
Administration of the placebo, which is identical-looking to the Aspirin and Rosuvastatin single capsule mixture, daily either orally or via a feeding tube for the duration of the patient's stay in the ICU.
干预措施: Placebo (for Aspirin and Rosuvastatin) (Drug)
结局指标
主要结局
Incidence of VTE
时间窗: Day 5 or ICU discharge or upon symptoms of VTE (whichever comes first)
Based on screening duplex ultrasound (US) of legs and central line on day 5 or upon ICU discharge or upon symptoms of VTE (whichever comes first).
次要结局
- Fibrinolysis Phenotypes(During ICU stay at the following timepoints - 6, 12, 24, 48, 72, 120 and 168 hours)
- Plasminogen Activator Inhibitor (PAI) - 1 and Tissue Plasminogen Activator (tPA) Levels in Plasma(During ICU stay at the following timepoints - 6, 12, 24, 48, 72, 120 and 168 hours)
- Incidence of Acute Lung Injury (ALI)(Within two weeks post-injury)
- Ventilator Free Days(Up to 28 days)
- Incidence of Arterial Thrombotic Complications: Myocardial Infarction (MI) and Cerebrovascular Accident (CVA).(Up to 28 days)
- All-cause Mortality(30 days)
- Intensive Care Unit (ICU) Days(28 days)
- Incidence of Multiple Organ Failure (MOF)(Up to 28 days)
研究者
Ernest E. Moore, MD
Professor of Surgery
Denver Health and Hospital Authority