Restart TICrH Alpha Pilot Protocol, Restarting DOACs After Traumatic Intracranial Hemorrhage

Sponsor

University of Texas at Austin (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04891861

Collaborator

University of Kansas (Other)

100

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Anticoagulants; Increased	Drug: Apixaban	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized trial of 1 versus 4 week DOAC restart after TICrHRandomized trial of 1 versus 4 week DOAC restart after TICrH

Masking:

Single (Outcomes Assessor)

Masking Description:

Central blinded assessment of endpoints

Primary Purpose:

Prevention

Official Title:

A Pilot Trial of Restarting Direct Oral Anticoagulants After Traumatic Intracranial Hemorrhage

Anticipated Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 week restart restart DOAC at 1 week post injury at label dose and frequency	Drug: Apixaban Direct Oral Anticoagulation all at label dose and frequency Other Names: Rivaroxaban Edoxaban Dabigatran
Active Comparator: 4 week restart restart DOAC at 4 weeks post injury at label dose and frequency	Drug: Apixaban Direct Oral Anticoagulation all at label dose and frequency Other Names: Rivaroxaban Edoxaban Dabigatran

Arm

Intervention/Treatment

Active Comparator: 1 week restart

restart DOAC at 1 week post injury at label dose and frequency

Drug: Apixaban

Direct Oral Anticoagulation all at label dose and frequency

Other Names:

Rivaroxaban

Edoxaban

Dabigatran

Active Comparator: 4 week restart

restart DOAC at 4 weeks post injury at label dose and frequency

Drug: Apixaban

Direct Oral Anticoagulation all at label dose and frequency

Other Names:

Rivaroxaban

Edoxaban

Dabigatran

Outcome Measures

Primary Outcome Measures

60-day composite endpoint [60 days]
A 60-day composite endpoint that includes the following clinical events: New or expansion of intracranial hemorrhage, other BARC3a or above major hemorrhage 28, stroke, systemic embolism, myocardial infarction, proximal lower extremity deep vein thrombosis, pulmonary embolism and cardiovascular death

Secondary Outcome Measures

Disability Rating Scale (0-29 scale range) [60 days]
Functional Measure
Modified Rankin Scale (0-6 scale range) [60 day]
Functional Measure
Standard Gamble [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)]
The standard gamble is the gold standard for analysis of decision making under uncertainty 7. It is an interview technique that begins with a description of a disease state. The patient is then asked to imagine suffering the disease and having a choice between taking a medication that might cure them but also might kill them. The so-called ping-pong method requires the interviewer to start with a hypothetical scenario of 0% probability of cure and 100% probability of a painless instant death. The interviewer then asks the patient if they would take the medication. He then flips the scenario, 100% cure, 0% death. He then goes back and forth between successive scenarios of lower death higher cure and lower cure higher death. Eventually, the patient settles at an equipoise and indecision of whether the risk of dying is worth incurring to take the medication and cure the disease. This is the patient's utility for that disease, expressed as a number between 0 and 1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 (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)
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:

Mechanical Valve or 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
Abbreviated Injury Scale other than head >3
Pregnancy
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
Completion of DOAC therapy expected prior to 60 day primary endpoint, e.g. 3-6 month VTE treatment
Concomitant need for strong inducers/inhibitors of p-gp and CYP3A4
Low body weight (<45kg)
Inability to swallow