Skip to main content
OpenTrials
Completed

NCT Number: NCT05898412

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

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.

Analysis of the data showed that 14 patients of the 218 patients included in the study (6.4%) experienced a thrombotic event (TE) within 30 days after treatment with andexanet alfa. The protocol was amended to allow for an in depth analysis of the 14 TE cases.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hemorrhage Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Research Site

Amsterdam, Netherlands

About this study

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.

The protocol was amended to allow for an in-depth analysis of the 14 individual cases who experienced a TE within 30 days after treatment with andexanet alfa, in order to establish the temporal relationships and clinical impact/outcome of this event on the patient, stratified by risk factors for the occurrence and outcome of the TE.

The results will be shown in a 'swimmers plot', showing the events relative to the onset of the major bleed and the clinical outcome of the TE, including risk classification based on the presence of co-morbidities and several risk factors such as TE and HF in medical history, weight/BMI, BP, restart DOAC, info on initial hemostasis, ICH/Chadvasc score, etc.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 18 years
  • Received at least one dose of andexanet alfa

Exclusion criteria

None

Treatment and study plan

Andexanet alfa

Drug

Patients treated with andexanet alfa

Primary outcomes

  1. Patient characteristics

    Time frame: Baseline (which is the date andexanet alfa is administered, i.e. indexdate)

    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.

    For 14 TE cases: weight, BMI anti-FXa level, type of blood transfusion, baseline haematoma volume (ICH only), bloodpressure parameters (initial, 1 hr, 2 hr, mean arterial pressure, 24hr control), pulse, noradrenalin, ICH score/Chadvasc score, do not resuscitate status, info on initial hemostasis that could inform on prognosis (if available from CT) will be described

Secondary outcomes

  1. Andexanet alfa dose

    Time frame: Baseline

    Dose of andexanet alfa in mg

  2. Time from symptom onset to hospital admission

    Time frame: Baseline

    time between the onset of the bleeding symptoms to admission to the hospital in hours

  3. Time from symptom onset to andexanet alfa administration

    Time frame: Baseline

    Time between onset of bleeding symptoms to start of the treatment with andexanet alfa in hours

  4. Time between last dose of FXai and andexanet alfa administration

    Time frame: Baseline

    Time between last dose of FXai taken by the patient and the start of the treatment with andexanet alfa in hours

  5. Frequency that andexanet alfa is administered before or after replacement therapy;

    Time frame: Baseline

    Number of times that a patient is treated with andexanet alfa in combination with replacement therapy

  6. Time interval between replacement therapy and andexanet alfa administration

    Time frame: Baseline

    Time between treatment with andexanet alfa and replacement therapy in hours

Other outcomes

  1. Cumulative incidence of thrombotic events

    Time frame: from index date to maximum 30 days FU

    Thrombotic events leading to (re-)hospitalization within 30 days after andexanet alfa treatment; thrombotic events occurring during the hospitalization for the index bleeding

    For 14 TE cases, the basis of the TE diagnosis (e.g. procedure, radiology, clinic, symptoms, lab etc) and the impact/outcome parameter of the TE will be described based on available information in the free text in EPD, varying from 'no impact' and 'severe impact' to 'death'

  2. Inpatient mortality

    Time frame: from index date to maximum 30 days FU

    Inpatient mortality within 30 days after andexanet alfa treatment

    For 14 TE cases, the cause of death and wether it was caused by a decision to terminate treatment will be described

  3. Rehospitalization

    Time frame: from index date to maximum 30 days FU

    All rehospitalizations (including diagnosis) within 30 days after andexanet alfa treatment

  4. Length Of Stay (LOS)

    Time frame: from index date to maximum 30 days FU

    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

  5. Number of surgical interventions

    Time frame: from index date to maximum 30 days FU

    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

  6. 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

  7. Number of CT scans and MRI's

    Time frame: from index date to maximum 30 days FU

    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

  8. Number of endoscopies

    Time frame: from index date to maximum 30 days FU

    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

  9. Type of anti-coagulant re-initiated after indexdate

    Time frame: from index date to maximum 30 days FU

    Type of any anti-coagulant that is reinitiated after index date

  10. Timing of any anti-coagulant re-initiated after index date

    Time frame: from index date to maximum 30 days FU

    Timing of any anti-coagulant that is reinitiated after index date in days

  11. Dose of any anti-coagulant re-initiated after index date

    Time frame: from index date to maximum 30 days FU

    Dose of any anti-coagulant that is reinitiated after index date in mg

  12. anticoagulant indication and dose, surgery activity date, andexanet alfa administration date

    Time frame: baseline

    To describe if andexanet alfa is administered to patients treated with edoxaban, enoxaparin or other anticoagulant or prior to acute surgery as primary indication

  13. Anti factor Xa activity measurement activities and results and timing of andexanet alfa adminstration

    Time frame: Baseline

    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

  14. Doselevel of andexanet alfa

    Time frame: Baseline

    it will be described whether the doselevel of andexanet alfa in mg, is related to the time between the last FXai administration and hospitalisation

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • LOGEX Healthcare Analytics Amsterdam The Netherlands

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Jun 12, 2023
Registry last updated
Apr 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.