- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05898412
Retrospective Study on Characteristics and Outcomes in Hospitalised Patients Treated With Ondexxya
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
Study Overview
Detailed Description
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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: AstraZeneca Clinical Study Information Center
- Phone Number: 1-877-240-9479
- Email: information.center@astrazeneca.com
Study Locations
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Amsterdam, Netherlands
- Recruiting
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Age ≥ 18 years
- Received at least one dose of andexanet alfa
Exclusion Criteria:
None
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Andexanet alfa
Hospitalized patients treated with andexanet alfa
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Patients treated with andexanet alfa
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient characteristics
Time Frame: Baseline (which is the date andexanet alfa is administered, i.e. indexdate)
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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
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Baseline (which is the date andexanet alfa is administered, i.e. indexdate)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Andexanet alfa dose
Time Frame: Baseline
|
Dose of andexanet alfa in mg
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Baseline
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Time from symptom onset to hospital admission
Time Frame: Baseline
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time between the onset of the bleeding symptoms to admission to the hospital in hours
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Baseline
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Time from symptom onset to andexanet alfa administration
Time Frame: Baseline
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Time between onset of bleeding symptoms to start of the treatment with andexanet alfa in hours
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Baseline
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Time between last dose of FXai and andexanet alfa administration
Time Frame: Baseline
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Time between last dose of FXai taken by the patient and the start of the treatment with andexanet alfa in hours
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Baseline
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Frequency that andexanet alfa is administered before or after replacement therapy;
Time Frame: Baseline
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Number of times that a patient is treated with andexanet alfa in combination with replacement therapy
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Baseline
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Time interval between replacement therapy and andexanet alfa administration
Time Frame: Baseline
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Time between treatment with andexanet alfa and replacement therapy in hours
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Baseline
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative incidence of thrombotic events
Time Frame: from index date to maximum 30 days FU
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Thrombotic events leading to (re-)hospitalization within 30 days after andexanet alfa treatment; thrombotic events occurring during the hospitalization for the index bleeding
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from index date to maximum 30 days FU
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Inpatient mortality
Time Frame: from index date to maximum 30 days FU
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Inpatient mortality within 30 days after andexanet alfa treatment
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from index date to maximum 30 days FU
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Rehospitalization
Time Frame: from index date to maximum 30 days FU
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All rehospitalizations (including diagnosis) within 30 days after andexanet alfa treatment
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from index date to maximum 30 days FU
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Length Of Stay (LOS)
Time Frame: from index date to maximum 30 days FU
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Total LOS and ICU LOS in days. These will be aggregated with the number of (i) surgical interventions to treat the bleeding,(ii) mechanical ventilation/intubation, (iii) brain CTs and MRIs and (iv) endoscopies to estimate the health care resource use |
from index date to maximum 30 days FU
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Number of surgical interventions
Time Frame: from index date to maximum 30 days FU
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Number of times that a surgical intervention is needed to treat the bleeding These will be aggregated with (i) LOS/ICU LOS and the the number of (ii) mechanical ventilation/intubation, (iii) brain CTs and MRIs and (iv) endoscopies to estimate the health care resource use |
from index date to maximum 30 days FU
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Number of mechanical ventilation/intubation
Time Frame: from index date to maximum 30 days FU
|
Number of times that a patient is intubated/ventilated mechanically These will be aggregated with (i) LOS/ICU LOS and the the number of (ii) surgical interventions (iii) brain CTs and MRIs and (iv) endoscopies to estimate the health care resource use |
from index date to maximum 30 days FU
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Number of CT scans and MRI's
Time Frame: from index date to maximum 30 days FU
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Number of CT scans and MRIs needed to diagnose the bleeding These will be aggregated with (i) LOS/ICU LOS and the the number of (ii) surgical interventions (iii) mechanical ventilation/intubation and (iv) endoscopies to estimate the health care resource use |
from index date to maximum 30 days FU
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Number of endoscopies
Time Frame: from index date to maximum 30 days FU
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Number of times that a an endoscopy is performed to diagnose/treat bleeding These will be aggregated with (i) LOS/ICU LOS and the the number of (ii) surgical interventions (iii) mechanical ventilation/intubation and (iv) brain CTs and MRIs to estimate the health care resource use |
from index date to maximum 30 days FU
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Type of anti-coagulant re-initiated after indexdate
Time Frame: from index date to maximum 30 days FU
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Type of any anti-coagulant that is reinitiated after index date
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from index date to maximum 30 days FU
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Timing of any anti-coagulant re-initiated after index date
Time Frame: from index date to maximum 30 days FU
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Timing of any anti-coagulant that is reinitiated after index date in days
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from index date to maximum 30 days FU
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Dose of any anti-coagulant re-initiated after index date
Time Frame: from index date to maximum 30 days FU
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Dose of any anti-coagulant that is reinitiated after index date in mg
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from index date to maximum 30 days FU
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anticoagulant indication and dose, surgery activity date, andexanet alfa administration date
Time Frame: baseline
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To describe if andexanet alfa is administered to patients treated with edoxaban, enoxaparin or other anticoagulant or prior to acute surgery as primary indication
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baseline
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Anti factor Xa activity measurement activities and results and timing of andexanet alfa adminstration
Time Frame: Baseline
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To describe if measurement of anti factor Xa activity prior to andexanet alfa administration is performed, and if results are available in time to impact clinical decision making
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Baseline
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Doselevel of andexanet alfa
Time Frame: Baseline
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it will be described whether the doselevel of andexanet alfa in mg, is related to the time between the last FXai administration and hospitalisation
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Baseline
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Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Coleman CI, Dobesh PP, Danese S, Ulloa J, Lovelace B. Real-world management of oral factor Xa inhibitor-related bleeds with reversal or replacement agents including andexanet alfa and four-factor prothrombin complex concentrate: a multicenter study. Future Cardiol. 2021 Jan;17(1):127-135. doi: 10.2217/fca-2020-0073. Epub 2020 Jul 3.
- Costa OS, Connolly SJ, Sharma M, Beyer-Westendorf J, Christoph MJ, Lovelace B, Coleman CI. Andexanet alfa versus four-factor prothrombin complex concentrate for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhage: a propensity score-overlap weighted analysis. Crit Care. 2022 Jun 16;26(1):180. doi: 10.1186/s13054-022-04043-8.
- Cohen AT, Lewis M, Connor A, Connolly SJ, Yue P, Curnutte J, Alikhan R, MacCallum P, Tan J, Green L. Thirty-day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life-threatening direct oral anticoagulant-related bleeding. J Am Coll Emerg Physicians Open. 2022 Mar 5;3(2):e12655. doi: 10.1002/emp2.12655. eCollection 2022 Apr.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- D9603R00007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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