Restarting Anticoagulation After Traumatic Intracranial Hemorrhage (Restart tICrH): a Prospective Randomized Open Label Blinded Endpoint (PROBE) Pragmatic Time-dose, Response Adaptive Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 1,100
- 试验地点
- 1
- 主要终点
- 60 Day Composite of Thrombotic and Bleeding Events
研究概览
简要总结
Primary Objective:
To identify the optimal interval to restart oral anticoagulation after traumatic intracranial hemorrhage that will minimize thrombotic events and major bleeding by performing a response adaptive randomized (RAR) PROBE clinical trial of restarting in anticoagulant-associated traumatic intracranial hemorrhage patients, comparing restart at 1 week to restart at 2 weeks or at 4 weeks, with a primary composite outcome of major thrombotic events and bleeding.
Primary Outcome: 60-day composite of thromboembolic events, defined as DVT, pulmonary emboli, myocardial infarctions, ischemic strokes and systemic emboli, and bleeding events defined as non-CNS major bleeding events (modified BARC3 or above) and worsening index tICrH or new intracranial hemorrhage (ICrH).
Secondary objectives of this trial include:
- To use the Trauma Quality Improvement Program (TQIP) of the American College of Surgeons - Committee on Trauma (ACS-COT), a well-established and highly respected trauma center oversight mechanism, to translate findings of the trial into practice in a closed loop.
- To establish a relationship between time of restarting and overall secondary events, i.e. a dose response, that favors early restarting (1 week is better than 2 weeks and 2 weeks is better than 4 weeks.
- To explore patient centered utility weighting of thrombotic versus bleeding composite endpoint components by: A) 60-day Disability Rating Scale (DRS) 24,25 and modified Rankin Scale (mRS)26; B) Trial patient-reported standard gamble utilities including by race, gender and ethnicity.
- To explore the composite without DVT in the thrombotic component
详细描述
Title: Restart tICrH Protocol Synopsis A Prospective Randomized Open Label Blinded Endpoint Response Adaptive Clinical Trial of Timing to Restart Direct Oral Anticoagulants After Traumatic Intracranial Hemorrhage
Objectives: To identify the optimal interval to restart oral anticoagulation after traumatic intracranial hemorrhage that will minimize thrombotic events and major bleeding by performing a response adaptive randomized (RAR) clinical trial of restarting in anticoagulant-associated traumatic intracranial hemorrhage patients, comparing restart at 1 week to restart at 2 weeks or at 4 weeks, with a primary composite outcome of major thrombotic events and bleeding.
Hypotheses: We hypothesize that restarting an oral anticoagulant at one week after anticoagulant-associated traumatic intracranial hemorrhage, compared to delayed restarting, reduces a composite outcome of major thrombotic events and major bleeding.
Study design Prospective, response adaptive randomized, open-label, blinded end-point (PROBE), 40 center national trial Study population -- Approximately 1100 participants with traumatic intracranial hemorrhage and an indication for Direct Oral Anticoagulant Main inclusion criteria
- Clinician intent to restart a Direct Oral Anticoagulant (DOAC) after anticoagulant-associated traumatic intracranial hemorrhage and equipoise concerning restart of anticoagulation at the specified time intervals.
- Acute traumatic intracranial hemorrhage on anticoagulation for Atrial Fibrillation (AF) or Venous Thromboembolism (VTE)
- Patient is higher risk for stroke or other thrombotic events as witnessed by having a CHA2DS2-VASc score of > 3
- DOAC will be prescribed at label dose with label adjustments for creatinine clearance. DOAC will be at continuation dose, i.e., not initial therapy high doses in the setting of VTE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
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
- •Entry into the trial is primarily driven pragmatically by clinician intent to restart a Direct Oral Anticoagulant (DOAC) after anticoagulant-associated traumatic intracranial hemorrhage and equipoise concerning restart of anticoagulation at the specified time intervals. DOAC will be at label dose with label adjustments for creatinine clearance. DOAC will be at continuation dose, i.e. not initial therapy high doses in the setting of VTE.
- •Acute traumatic intracranial hemorrhage on anticoagulation for Atrial Fibrillation (AF) or Venous Thromboembolism (VTE) or both (2,500 patients per year at our 40 sites)
- •Patient is higher risk for stroke or other thrombotic events as witnessed by having a CHA2DS2-VASc score of > 3 (at least 3 of the following risk factors: age greater than 65,( age > 75 counts for two points), history of stroke or TIA, history of heart failure, history of diabetes, history of atherosclerotic vascular disease, female gender, history of hypertension) (Excludes 20% or 500 patients per year)
排除标准
- •Mechanical Valve
- •Ventricular Assist Device (VAD)
- •SDH >8 mm maximum width or any midline shift at any time point or more than one SDH
- •Physician plan to start/restart antiplatelet therapy during trial period
- •Acute Injury Score other than head >=3
- •Inability to understand need for adherence to study protocol
- •Renal function below DOAC label exclusions
- •Any active pathological bleeding (e.g. no acute blood on most recent CT)
- •Hypersensitivity to drug or other label contraindication
- •Any bleeding that the investigator deems unsafe to restart DOAC at 1 week post injury, or conversely unsafe to hold DOAC to 4 weeks
- •Expected completion of DOAC therapy expected prior to 60 day primary outcome, e.g. 3-6 month VTE therapy
- •Concomitant need for strong inducers/inhibitors of p-gp and CYP3A4
研究组 & 干预措施
1 week
Time to delay the initiation of anticoagulation is determined at randomization. Patients will be randomized to initiate anticoagulation 1 week, 2 weeks, or 4 weeks following injury.
干预措施: Anticoagulants (Drug)
2 weeks
Time to delay the initiation of anticoagulation is determined at randomization. Patients will be randomized to initiate anticoagulation 1 week, 2 weeks, or 4 weeks following injury.
干预措施: Anticoagulants (Drug)
4 weeks
Time to delay the initiation of anticoagulation is determined at randomization. Patients will be randomized to initiate anticoagulation 1 week, 2 weeks, or 4 weeks following injury.
干预措施: Anticoagulants (Drug)
结局指标
主要结局
60 Day Composite of Thrombotic and Bleeding Events
时间窗: 60 days following index bleeding event
Composite of Thrombotic events, defined as DVT, PE, MI, Ischemic Strokes, and systemic emboli, cardiovascular death along with bleeding events defined as non-CNS major bleeding, worsening index tICrH, or new intracranial hemorrhage.
次要结局
- 60 Day Modified Rankin Scale (1-6 with 6 being worse)(60 days following index bleeding event)
- 60 Day Disability Rating Scale (1-29 with 29 being worse)(60 days following index bleeding event)
- Standard Gamble Patient Reported utilities for endpoints(pre-randomization and after endpoints)
研究者
Truman J Milling Jr
Associate Professor of Neurology
University of Texas at Austin