Restarting Anticoagulation After Traumatic Intracranial Hemorrhage

• Status: Not yet recruiting
• Trial end date: 2027-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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:

1. 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.

2. 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.

3. 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.

4. To explore the composite without DVT in the thrombotic component

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Texas at Austin
• Treatments: Anticoagulants

Criteria

Inclusion Criteria:

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.

1. 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)

2. 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)

Exclusion Criteria:

1. Mechanical Valve

2. Ventricular Assist Device (VAD)

3. SDH >8 mm maximum width or any midline shift at any time point or more than one SDH

4. Physician plan to start/restart antiplatelet therapy during trial period

5. Acute Injury Score other than head >=3

6. Pregnancy

7. Inability to understand need for adherence to study protocol

8. Renal function below DOAC label exclusions

9. Any active pathological bleeding (e.g. no acute blood on most recent CT)

10. Hypersensitivity to drug or other label contraindication

11. Any bleeding that the investigator deems unsafe to restart DOAC at 1 week post injury, or conversely unsafe to hold DOAC to 4 weeks

12. Expected completion of DOAC therapy expected prior to 60 day primary outcome, e.g. 3-6 month VTE therapy

13. Concomitant need for strong inducers/inhibitors of p-gp and CYP3A4