Retrospective Study on Characteristics and Outcomes in Hospitalised Patients Treated With Ondexxya

Study Overview
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Brief Summary
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This is an observational retrospective database study of hospitalized patients treated with andexanet alfa in approximately 10 Dutch hospitals. Currently there is limited information on the patient characteristics and outcomes of patients who are treated with andexanet alfa in The Netherlands and how it is used. This is of interest for treating clinicians because there is a need for a patient profile, also due to the on par position of andexanet alfa with PCC in the Dutch national guideline.

Detailed Description
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The direct oral anticoagulants (DOAC) rivaroxaban and apixaban inhibit factor Xa (FXa) and are widely used in clinical practice, due to the ease of administration, lack of need for frequent monitoring and dose adjustment and an improved safety profile. However, reversal of the anticoagulant effect of these FXa inhibitors (FXai) can be acutely required in case of serious bleeding events, like intracranial hemorrhage (ICH). Ondexxya® (andexanet alfa) has been approved and is available in the Netherlands since 2019. Andexanet alfa is a modified FXa with no coagulant activity. It has a high binding affinity to DOACs and can therefore be used as reversal agent against DOACs. However, andexanet alfa is not used in all Dutch centers. In some hospitals, instead of andexanet alfa, nonspecific agents are used to manage FXai-associated ICH bleeding, like four-factor prothrombin complex concentrate (4F-PCC). Due to the on par position of andexanet alfa and 4F-PCC in the Dutch multidisciplinary antithrombotic guideline, there is no clear patient profiling for the use of andexanet alfa for Dutch clinicians. The lack of randomized clinical trials comparing the efficacy and safety of andexanet alfa and 4F-PCC also does not help to provide clarity. There is real world evidence data available (Coleman et al. 2020; Cohen et al. 2022; Costa et al. 2022) but these studies uses data from the US and the UK, and consistently report a superior effectiveness of andexanet alfa over 4F-PCC. However, there is considerable variation in the reported effectiveness between these studies, with mortality rate ranging from 4% to 15.3%. Potentially, differences in methodology and sample size, in addition to patient populations and bleeding locations varying between analyses, have resulted in this variation. Additionally, anecdotal information indicates that in some cases andexanet alfa is administered after 4F-PCC fails. Therefore, the aim of the present analysis is to characterize the patient population that received andexanet alfa in the Dutch healthcare system. Also, we aim to describe clinical outcomes in patients treated with andexanet alfa in daily clinical practice in the Netherlands. Providing real world data on the patient characteristics and outcomes of andexanet alfa treated patients in the Netherlands, may support clinicians in the future identification of the patient who benefit most of treatment with andexanet alfa.

Official Title
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Retrospective Real World Evidence Study to Describe Characteristics and Outcomes in Dutch Patients Admitted to the Hospital With a Factor Xa Inhibitor-associated Bleeding Treated With Andexanet Alfa

Conditions
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Hemorrhage

Intervention / Treatment
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* Drug: Andexanet alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Received at least one dose of andexanet alfa Exclusion Criteria: None

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 |
| --- | --- |
| Andexanet alfa<br>Hospitalized patients treated with andexanet alfa | Drug: Andexanet alfa<br>* Patients treated with andexanet alfa<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient characteristics | At baseline the following patient characteristics will be described: age, sex, type of bleeding (ICH, GI or other), concomittant medication, FXai indication, type and dose, comorbidities, GCS at admission (for ICH only), eGFR and Hb, type of hospital | Baseline (which is the date andexanet alfa is administered, i.e. indexdate) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Andexanet alfa dose | Dose of andexanet alfa in mg | Baseline | 
| Time from symptom onset to hospital admission | time between the onset of the bleeding symptoms to admission to the hospital in hours | Baseline | 
| Time from symptom onset to andexanet alfa administration | Time between onset of bleeding symptoms to start of the treatment with andexanet alfa in hours | Baseline | 
| Time between last dose of FXai and andexanet alfa administration | Time between last dose of FXai taken by the patient and the start of the treatment with andexanet alfa in hours | Baseline | 
| Frequency that andexanet alfa is administered before or after replacement therapy; | Number of times that a patient is treated with andexanet alfa in combination with replacement therapy | Baseline | 
| Time interval between replacement therapy and andexanet alfa administration | Time between treatment with andexanet alfa and replacement therapy in hours | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Observational, Retrospective, Major bleeding, Andexanet alfa, Factor Xa inhibitor, Patient characteristics, Treatment strategy, Outcomes