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

Anticoagulants; Increased Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04891861
• Other study ID #: ML42205
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 1, 2021
• Est. completion date: July 1, 2023

Study information

• Verified date: May 2021
• Source: University of Texas at Austin
• Contact: Truman J Milling, MD
• Phone: 5124969742
• Email: tmilling[@]ascension.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: July 1, 2023
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anticoagulants; Increased
• Hemorrhage
• Intracranial Hemorrhage, Traumatic
• Intracranial Hemorrhages

Intervention

Drug:
• Apixaban
Direct Oral Anticoagulation all at label dose and frequency

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas at Austin	University of Kansas

References & Publications (1)

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 Tra — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	60 days
Secondary	Disability Rating Scale (0-29 scale range)	Functional Measure	60 days
Secondary	Modified Rankin Scale (0-6 scale range)	Functional Measure	60 day
Secondary	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.	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)