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

Hemorrhage Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05898412
• Other study ID #: D9603R00007
• Status: Recruiting
• Start date: October 6, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Received at least one dose of andexanet alfa

Exclusion Criteria:

None

Related Conditions & MeSH terms

• Hemorrhage

Intervention

Drug:
• Andexanet alfa
Patients treated with andexanet alfa

Locations

Country	Name	City	State
Netherlands	Research Site	Amsterdam

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	LOGEX Healthcare Analytics Amsterdam The Netherlands

Country where clinical trial is conducted

Netherlands, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cumulative incidence of thrombotic events	Thrombotic events leading to (re-)hospitalization within 30 days after andexanet alfa treatment; thrombotic events occurring during the hospitalization for the index bleeding	from index date to maximum 30 days FU
Other	Inpatient mortality	Inpatient mortality within 30 days after andexanet alfa treatment	from index date to maximum 30 days FU
Other	Rehospitalization	All rehospitalizations (including diagnosis) within 30 days after andexanet alfa treatment	from index date to maximum 30 days FU
Other	Length Of Stay (LOS)	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
Other	Number of surgical interventions	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
Other	Number of mechanical ventilation/intubation	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
Other	Number of CT scans and MRI's	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
Other	Number of endoscopies	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
Other	Type of anti-coagulant re-initiated after indexdate	Type of any anti-coagulant that is reinitiated after index date	from index date to maximum 30 days FU
Other	Timing of any anti-coagulant re-initiated after index date	Timing of any anti-coagulant that is reinitiated after index date in days	from index date to maximum 30 days FU
Other	Dose of any anti-coagulant re-initiated after index date	Dose of any anti-coagulant that is reinitiated after index date in mg	from index date to maximum 30 days FU
Other	anticoagulant indication and dose, surgery activity date, andexanet alfa administration date	To describe if andexanet alfa is administered to patients treated with edoxaban, enoxaparin or other anticoagulant or prior to acute surgery as primary indication	baseline
Other	Anti factor Xa activity measurement activities and results and timing of andexanet alfa adminstration	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	Baseline
Other	Doselevel of andexanet alfa	it will be described whether the doselevel of andexanet alfa in mg, is related to the time between the last FXai administration and hospitalisation	Baseline
Primary	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	Andexanet alfa dose	Dose of andexanet alfa in mg	Baseline
Secondary	Time from symptom onset to hospital admission	time between the onset of the bleeding symptoms to admission to the hospital in hours	Baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	Time interval between replacement therapy and andexanet alfa administration	Time between treatment with andexanet alfa and replacement therapy in hours	Baseline