Clinical trial NCT04891861: Restart TICrH Alpha Pilot Protocol, Restarting DOACs After Traumatic Intracranial Hemorrhage
Official title: A Pilot Trial of Restarting Direct Oral Anticoagulants After Traumatic Intracranial Hemorrhage
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Anticoagulants; Increased
Keywords: restart
anticoagulant
DOAC
Lead sponsor: University of Texas at Austin
Sponsor class: OTHER
Collaborators: name: University of Kansas
First posted: 2021-05-19
Enrollment: 100
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized trial of 1 versus 4 week DOAC restart after TICrH
Primary purpose: PREVENTION

Brief summary: Randomized pilot trial of restarting DOACs at 1 week versus 4 weeks after traumatic intracranial hemorrhage

Detailed description: Restart TICrH two-center pilot trial will assign patients with anticoagulant-associated traumatic intracranial hemorrhage to restart anticoagulation at 1 week or 4 weeks. Entry into the trial is primarily driven pragmatically by clinician intent to restart any Direct Oral Anticoagulant (DOAC, i.e. apixaban, rivaroxaban, edoxaban, dabigatran. There is no head to head evidence of superiority of any drug) 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.

Eligibility criteria: Inclusion Criteria:

1. Acute traumatic intracranial hemorrhage on anticoagulation for Atrial Fibrillation (AF) or Venous Thromboembolism (VTE)
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 2 points), history of stroke or TIA (2 points), history of heart failure, history of diabetes, history of atherosclerotic vascular disease, female biological sex, history of hypertension)
3. DOAC prescribed at label dose with creatinine clearance adjustments. DOAC at continuation dose, i.e., not initial therapy high doses in the setting of VTE

Exclusion Criteria:

1. Mechanical Valve or Ventricular Assist Device (VAD)
2. SDH \>8 mm maximum width or any midline shift at any time point or more than one SDH
3. Physician plan to start/restart antiplatelet therapy during trial period
4. Abbreviated Injury Scale other than head \>3
5. Pregnancy
6. Inability to understand need for adherence to study protocol
7. Renal function below DOAC label exclusions
8. Any active pathological bleeding (e.g. no acute blood on most recent CT)
9. Hypersensitivity to drug or other label contraindication
10. Any bleeding that the investigator deems unsafe to restart DOAC at 1 week post injury, or conversely unsafe to hold DOAC to 4 weeks
11. Completion of DOAC therapy expected prior to 60 day primary endpoint, e.g. 3-6 month VTE treatment
12. Concomitant need for strong inducers/inhibitors of p-gp and CYP3A4
13. Low body weight (\<45kg)
14. Inability to swallow

Primary outcomes:
measure: 60-day composite endpoint
timeFrame: 60 days
Secondary outcomes:
measure: Disability Rating Scale (0-29 scale range)
timeFrame: 60 days
measure: Modified Rankin Scale (0-6 scale range)
timeFrame: 60 day
measure: Standard Gamble
timeFrame: pre-randomization (The day before randomization, which must occur within 6 days of index injury) and after endpoints (the day after one of the endpoints occurs. We cannot know precisely when this will occur in the 60 day follow up period)
Other outcomes:
Locations:
Study officials:
References:
citation: Milling TJ Jr, Warach S, Johnston SC, Gajewski B, Costantini T, Price M, Wick J, Roward S, Mudaranthakam D, Dula AN, King B, Muddiman A, Lip GYH. Restart TICrH: An Adaptive Randomized Trial of Time Intervals to Restart Direct Oral Anticoagulants after Traumatic Intracranial Hemorrhage. J Neurotrauma. 2021 Jun 1;38(13):1791-1798. doi: 10.1089/neu.2020.7535. Epub 2021 Apr 6.