Andexanet Alfa: Non-interventional Study in Stroke Units in Germany (DE)

Study Overview
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Brief Summary
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The multicenter, prospective, observational, non-interventional study conducted in German Stroke Units is investigating patients with intracranial hemorrhage (ICH) under effective anticoagulation with rivaroxaban or apixaban. The aim of the study is to analyze under routine conditions wether the volume increase of ICH under treatment with rivaroxaban and apixaban can be reduced with the antidote andexanet alfa. Thus, data of patients under effective treatment with rivaroxaban or apixaban and treated with andexanet alfa at baseline will be assessed at the time of onset of ICH, during the hospital stay and during a follow-up by telephone at 30 and 90 days after hospital discharge. The main objective is defined as the change in size or volume of the hematoma by computed tomography (CT) or magnetic resonance imaging (MRI) in patients with ICH under effective treatment with rivaroxaban and apixaban, who are treated with andexanet alfa. Further objectives comprise evaluations concerning the functional status according to modified Rankin Scale (mRS), changes in the National Institutes of Health Stroke Scale (NIHSS), and occurrences of ICH or new intraventricular bleeding as well as mortality rates.

Official Title
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Andexanet Alfa: Non-interventional Study in Stroke Units in Germany (DE)

Conditions
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Intracranial Hemorrhages

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years at enrollment Patients willing and able to provide written informed consent for data transmission. For patients who are not legally competent to sign this informed consent for data transmission exceptions/special cases are defined (details provided in the study protocol) Patients with primary intracranial hemorrhage as confirmed with CT or MRI. Patients under effective anticoagulation treatment with rivaroxaban or apixaban at the time of admission, according to the judgement of treating physician and determined using Point-of-care (PoC) anti-factor Xa (fXa) assays or laboratory-based anti-fXa measurement. Patients treated with andexanet alfa Signed informed consent as soon as possible after start of symptoms of initial ICH event, but before discharge Exclusion Criteria: Start of symptoms of initial ICH event > 24 h before admission to hospital

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient group<br>Patients under effective anticoagulation with rivaroxaban or apixaban and treated with andexanet alfa | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in size (specified as ml or cm^3) of the intracranial bleeding evaluated by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) | The primary endpoint is the change in size (specified as ml or cm^3) of the intracranial bleeding evaluated by first CT or MRI between 12-72 hours after initial CT or MRI; further imaging in case of worsened health condition | 12-72 hours after initial CT or MRI, further imaging in case of worsened health condition | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional status according to modified Rankin Scale (mRS) | Functional status acc. to modified Rankin Scale (mRS) before ICH, at admission, at discharge, after 30 days, and after 90 days. The mRS ranges from grade 0 (no symptoms) to grade 6 (dead) | before ICH, at admission, at discharge, after 30 days, and after 90 days | 
| Mortality rate | Mortality rate after 7, 30 and 90 days, and intra-hospital mortality rate | after 7, 30 and 90 days und during hospital stay | 
| Rate of worsened health condition | Rate of worsened health condition defined as change in NIHSS of ≥4 pts compared to initial NIHSS or worsening of NIHSS level of consciousness ≥1 point or increase of the volume of the intracranial bleeding or new intraventricular bleeding or death | At hospital admission and additionally at 24 hours and 72 hours after admission | 
| Change in severity of stroke | Change in severity of stroke based on the National Institutes of Health Stroke Scale (NIHSS) 72 hours after admission | 72 hours after admission | 
| Assessment of effective anticoagulation at baseline | Assessment of effective anticoagulation at baseline using PoC anti-fXa assay, intra-hospital decision making for Andexanet alfa administration | at baseline | 
| Clinical course and outcomes of patients | Hemostasis will be assessed by coagulation parameters (activated partial thrombin time (aPTT), thrombin time (TT), International Normalized Ratio (INR)) at admission, re-bleeding and thrombotic events (e.g. myocardial infarction, ischemic stroke, deep vein thrombosis) will be assessed by AE reporting performed from admission to hospital to discharge | Coagulation parameters will be recorded at hospital admission. Thrombotic events and re-bleeding will be recorded from the date of hospital admission until discharge. The average length of hospital stay is expected to be 10 days | 
| Re-dosing and re-anticoagulation therapy | Resumption of antithrombotic therapy in hospital (incl. type, start date and dose of anticoagulation therapy) | The assessement of re-dosing and re-anticoagulation therapy will take place from the date of hospital admission until the date of discharge. The average length of hospital stay is expected to be 10 days. | 
| Health care resource utilization (including ICU length of stay) | Data regarding ICU length of stay and on resource utilization (Intubated on arrival, Mechanical ventilation, ICH-evacuation surgery, External ventricular drainage, Intraventricular lysis, Osmotherapy) | Will be recorded during hospital stay until the date of discharge.The average length of hospital stay is expected to be 10 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intracranial bleeding, Andexanet-alfa, Rivaroxaban, Apixaban, Anticoagulation