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

Primary Purpose

Anticoagulants; Increased

Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Apixaban
Sponsored by
University of Texas at Austin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Anticoagulants; Increased focused on measuring restart, anticoagulant, DOAC

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Active Comparator

    Arm Label

    1 week restart

    4 week restart

    Arm Description

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

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

    Outcomes

    Primary Outcome Measures

    60-day composite endpoint
    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)
    Functional Measure
    Modified Rankin Scale (0-6 scale range)
    Functional Measure
    Standard Gamble
    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.

    Full Information

    First Posted
    May 10, 2021
    Last Updated
    May 14, 2021
    Sponsor
    University of Texas at Austin
    Collaborators
    University of Kansas
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04891861
    Brief Title
    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

    2. Study Status

    Record Verification Date
    May 2021
    Overall Recruitment Status
    Unknown status
    Study Start Date
    July 1, 2021 (Anticipated)
    Primary Completion Date
    July 1, 2023 (Anticipated)
    Study Completion Date
    July 1, 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Texas at Austin
    Collaborators
    University of Kansas

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Anticoagulants; Increased
    Keywords
    restart, anticoagulant, DOAC

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Randomized trial of 1 versus 4 week DOAC restart after TICrH
    Masking
    Outcomes Assessor
    Masking Description
    Central blinded assessment of endpoints
    Allocation
    Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    1 week restart
    Arm Type
    Active Comparator
    Arm Description
    restart DOAC at 1 week post injury at label dose and frequency
    Arm Title
    4 week restart
    Arm Type
    Active Comparator
    Arm Description
    restart DOAC at 4 weeks post injury at label dose and frequency
    Intervention Type
    Drug
    Intervention Name(s)
    Apixaban
    Other Intervention Name(s)
    Rivaroxaban, Edoxaban, Dabigatran
    Intervention Description
    Direct Oral Anticoagulation all at label dose and frequency
    Primary Outcome Measure Information:
    Title
    60-day composite endpoint
    Description
    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
    Time Frame
    60 days
    Secondary Outcome Measure Information:
    Title
    Disability Rating Scale (0-29 scale range)
    Description
    Functional Measure
    Time Frame
    60 days
    Title
    Modified Rankin Scale (0-6 scale range)
    Description
    Functional Measure
    Time Frame
    60 day
    Title
    Standard Gamble
    Description
    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.
    Time Frame
    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)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Truman J Milling, MD
    Phone
    5124969742
    Email
    tmilling@ascension.org
    First Name & Middle Initial & Last Name or Official Title & Degree
    Steven Warach, MD PhD
    Email
    steven.warach@austin.utexas.edu

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Sharing via BIOLINCC
    IPD Sharing Time Frame
    After primary publication
    Citations:
    PubMed Identifier
    33470152
    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.
    Results Reference
    result

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