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Restarting Anticoagulation After Traumatic Intracranial Hemorrhage (Restart tICrH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04229758
Recruitment Status : Not yet recruiting
First Posted : January 18, 2020
Last Update Posted : May 19, 2021
Sponsor:
Information provided by (Responsible Party):
Truman J Milling Jr, University of Texas at Austin

Brief 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

Condition or disease Intervention/treatment Phase
Hemorrhage Intracranial Hemorrhages Bleeding Trauma Drug: Anticoagulants Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The trial will employ an innovative adaptive design using time as a dose (1, 2 and 4 weeks) and adapting randomization probabilities to the better performing doses with a PROBE model to minimize surveillance bias.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Restarting Anticoagulation After Traumatic Intracranial Hemorrhage (Restart tICrH): a Prospective Randomized Open Label Blinded Endpoint (PROBE) Pragmatic Time-dose, Response Adaptive Clinical Trial
Estimated Study Start Date : October 2021
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : February 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Anticoagulants
DOAC for the prevention of thromboembolic events in patients with non-valvular AF or VTE.

Experimental: 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.
Drug: Anticoagulants
DOAC for the prevention of thromboembolic events in patients with non-valvular AF or VTE.

Experimental: 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.
Drug: Anticoagulants
DOAC for the prevention of thromboembolic events in patients with non-valvular AF or VTE.




Primary Outcome Measures :
  1. 60 Day Composite of Thrombotic and Bleeding Events [ Time Frame: 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.


Secondary Outcome Measures :
  1. 60 Day Disability Rating Scale (1-29 with 29 being worse) [ Time Frame: 60 days following index bleeding event ]
    DRS is a scale to measure disability after an injury

  2. 60 Day Modified Rankin Scale (1-6 with 6 being worse) [ Time Frame: 60 days following index bleeding event ]
    The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.

  3. Standard Gamble Patient Reported utilities for endpoints [ Time Frame: pre-randomization and after endpoints ]
    Performed prior to randomization and immediately after each endpoint



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04229758


Contacts
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Contact: Truman J Milling, MD 5124969742 tmilling@ascension.org
Contact: Patrick Lawrence patrick.lawrence@austin.utexas.edu

Locations
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United States, Texas
Dell Seton Medical Center at The University of Texas
Austin, Texas, United States, 78701
Sponsors and Collaborators
University of Texas at Austin
Investigators
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Principal Investigator: Truman J Milling, MD Seton Dell Medical School Stroke Institute
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Responsible Party: Truman J Milling Jr, Associate Professor of Neurology, University of Texas at Austin
ClinicalTrials.gov Identifier: NCT04229758    
Other Study ID Numbers: 2020090035
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: May 19, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Sharing of data generated by this project is an essential part of our proposed activities. Following study completion, the DCC staff will follow National Trauma Research Repository (NTRR) and NHLBI's Biologic Specimen and Data Repository Information Coordinating Center (BioLLINCC) policies to upload the study's final de-identified data set, supporting documentation (data dictionary, protocol, consent form, data analysis plans) and any manuscripts. The final data set will be a csv file upload that is consistent with the NTRR data element attributes and characteristics.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: After publication of primary manuscript

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Truman J Milling Jr, University of Texas at Austin:
Anticoagulation
Anticoagulant
Anticoagulants
Restart
Delay
Hemorrhage
ICH
SAH
SDH
DOAC
NOAC
apixaban
rivaroxaban
edoxaban
Additional relevant MeSH terms:
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Intracranial Hemorrhages
Intracranial Hemorrhage, Traumatic
Hemorrhage
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Anticoagulants