Anticoagulation Therapy Timing in Atrial Fibrillation After Acute and Chronic Subdural Hematoma

Study Overview
=================
Brief Summary
-----------------
Subdural hematoma (SDH) is a common disorder that typically results from head trauma and has increased in prevalence in recent decades. Acute subdural hematomas (aSDH) are found in up to one-third of patients with severe traumatic brain injury and are associated with an unfavorable outcome in the majority of cases. Chronic subdural hematomas (cSDH) commonly occur in the elderly population which has highest risk for developing cSDH with or without minor head injuries. The combination of the aging population, higher incidence of disease in progressively older patients, and high morbidity and mortality renders SDH a growing problem within Canada with significant health-systems burden. SDH commonly recurs even after successful surgical drainage. Atrial fibrillation (AF) is one of the most common medical comorbidities in patients with cSDH, especially in the elderly, with an expected doubling of its prevalence by the year 2030. Patients with AF are at recognized risk for stroke, so anticoagulation is indicated for almost all patients. Anticoagulation is held prior to SDH drainage to minimize the risk of intraoperative and early postoperative bleeding. After surgery, the risk of SDH recurrence must be balanced against the risk of thromboembolic events such as stroke when deciding the timing of resuming anticoagulation. Currently the decision on when to restart anticoagulation after SDH is made by clinicians on an individual patient basis without any high-quality evidence to guide this decision. The two most common approaches are: 1) early resumption of anticoagulation after 30 days of diagnosis or surgery; and 2) delayed resumption of anticoagulation after 90 days of diagnosis or surgery. However, which of these approaches leads to the best functional outcomes for patients is unclear. Our pilot RCT will test the feasibility of comparing these 2 approaches in a larger multicenter RCT.

Official Title
-----------------
Pilot Randomized Controlled Trial of Anticoagulation Therapy Timing in Atrial Fibrillation After Acute and Chronic Subdural Hematoma (ATTAACH)

Conditions
-----------------
Subdural Hematoma, Atrial Fibrillation

Intervention / Treatment
-----------------
* Drug: Direct Acting Oral Anticoagulant starting at Day 30
* Drug: Direct Acting Oral Anticoagulant starting at Day 90


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥18 years of age Any SDH, defined as either acute or encapsulated partially liquefied hematoma in the subdural space diagnosed on a CT scan Can have surgical drainage (either burr hole or craniotomy) for aSDH and cSDH On therapeutic anticoagulation (DOAC or warfarin) as standard of care therapy prior to presentation for stroke prophylaxis secondary to AF Exclusion Criteria: aSDH requiring decompressive craniectomy Mechanical heart valve or moderate to severe mitral stenosis Known chronic coagulopathy (elevated INR >1.5 or PTT>40s after anticoagulant reversal, thrombocytopenia with platelet count <50x109/L) that is not amenable to reversal >37 days has elapsed since initial diagnosis without recruitment into the trial Active gastroduodenal ulcer, urogenital or respiratory tract hemorrhage Known pregnancy or breastfeeding Indication for therapeutic anticoagulation other than AF Pre-randomization brain CT at 2-4 weeks after initial diagnosis or surgery date reveals significant recurrence requiring surgical drainage Known to be non-compliant with prior anticoagulant MRP decides to restart Warfarin (as opposed to DOACs) as prophylactic anticoagulant as part of standard therapy for the patient after cSDH or aSDH

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early resumption of anticoagulation<br>The standard of care DOAC at appropriate standard dose assigned by the MRP will start at day 30 +/- 7 after diagnosis of acute or chronic subdural hematoma. | Drug: Direct Acting Oral Anticoagulant starting at Day 30<br>* Dabigatran, Rivaroxaban, Apixaban or Edoxaban at standard dose as recommended by the MRP<br>|
| Active Comparator: Delayed resumption of anticoagulation<br>The standard of care DOAC at appropriate standard dose assigned by the MRP will start at day 90 +/- 14 after diagnosis of acute or chronic subdural hematoma. | Drug: Direct Acting Oral Anticoagulant starting at Day 90<br>* Dabigatran, Rivaroxaban, Apixaban or Edoxaban at standard dose as recommended by the MRP<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | The number of participants enrolled for each participating institution, measured as the rate of consent for patients meeting eligibility criteria in one year per institution. Reasons for non-enrollment of eligible patients will be recorded | 1 year | 
| Implementation of study protocol | The proportion of enrolled participants who have completed follow-up measures at 90 days with complete recording of the functional outcome degree of disability | Study completion  2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional outcome - Degree of disability | Level of disability measured by the modified Rankin Scale (mRS). The mRS is a core instrument used for measuring the degree of disability or dependence in activities of daily living that is sensitive to thromboembolic and hemorrhagic complications. It is a clinician-reported measure and widely applied for evaluating stroke patient outcomes. It is a 7-level ordered categorical scale with scores ranging from 0 (no symptoms/disability) to 6 (death). The analysis will be categorized as favourable outcome (scores 0-3) versus unfavourable outcome (scores 4-6) | 90 days | 
| Functional outcome - Degree of disability | Level of disability measured by the modified Rankin Scale (mRS). The mRS is a core instrument used for measuring the degree of disability or dependence in activities of daily living that is sensitive to thromboembolic and hemorrhagic complications. It is a clinician-reported measure and widely applied for evaluating stroke patient outcomes. It is a 7-level ordered categorical scale with scores ranging from 0 (no symptoms/disability) to 6 (death). The analysis will be categorized as favourable outcome (scores 0-3) versus unfavourable outcome (scores 4-6) | 180 days | 
| Functional outcome - Stroke-related neurologic deficit | Measured using the National Institute of Health Stroke Scale (NIHSS) which is a 15-item impairment scale. It groups scores into categories based on severity, ranging from mild to very severe, with a higher score indicating a greater degree of impairment | 90 days | 
| Functional outcome - Stroke-related neurologic deficit | Measured using the National Institute of Health Stroke Scale (NIHSS) which is a 15-item impairment scale. It groups scores into categories based on severity, ranging from mild to very severe, with a higher score indicating a greater degree of impairment | 180 days | 
| Incidence of intracranial hemorrhage | The composite outcome of clinically-important intracranial hemorrhage defined by: 1) any increase in volume of blood in the CT of at least 33%; 2) need for surgical evacuation of SDH or repeat surgical evacuation; 3) death directly related to enlarging SDH or new parenchymal bleed; 4) symptomatic bleeding in a critical non-intracranial region | Continuous, baseline to 180 days | 
| Incidence of thromboembolic events | Composite outcome of clinically-important thromboembolic events defined as any of: 1) symptomatic TIA; 2) symptomatic objectively-confirmed ischemic stroke; 3) symptomatic, objectively-confirmed non-CNS systemic embolism; 4) objectively proven VTE; 5) all death directly or indirectly caused by a thrombotic event | Continuous, baseline to 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Direct-acting Oral Anticoagulants