An observational study in Traumatic Brain Injury and Intracranial Hemorrhages, sponsored by University Medical Centre Ljubljana. Completed at 1 site in Slovenia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by University Medical Centre Ljubljana · Observational
Elderly patients on direct oral anticoagulants (DOACs), specifically factor Xa (FXa) inhibitors such as apixaban and rivaroxaban are at elevated risk of haematoma expansion following traumatic brain injury (TBI). Andexanet alfa is a recombinant modified factor Xa decoy protein that directly reverses the anticoagulant effect of FXa inhibitors. The pivotal ANNEXA-4 single-arm trial reported hemostatic efficacy of approximately 82% in the overall cohort and 82.9% among patients with intracranial haemorrhage (ICH). The subsequent ANNEXA-I randomised controlled trial demonstrated 67.0% hemostatic efficacy with andexanet alfa compared with 53.1% in the usual-care group (adjusted difference 13.4 percentage points; p=0.003) among patients with spontaneous ICH. However, both landmark trials were focused predominantly on spontaneous ICH, and TBI-specific real-world data on andexanet alfa remain limited.
This retrospective single-centre cohort study evaluates the hemostatic efficacy and safety of andexanet alfa in adult patients with traumatic intracranial haemorrhage who were received FXa inhibitor anticoagulation. All patients had a baseline computed tomography (CT) scan and at least one follow-up CT within 24 hours of andexanet alfa administration. The primary outcome is the proportion of patients achieving excellent or good hemostatic efficacy, defined by the percentage change in haematoma volume (for intraparenchymal haemorrhage, IPH) or maximum thickness (for subdural haematoma, SDH; epidural haematoma, EDH; or subarachnoid haemorrhage, SAH) between baseline and follow-up CT: Excellent (≤20% increase), Good (21-35% increase), or Poor (>35% increase). Key secondary outcomes include 30-day all-cause mortality, thrombotic complications (deep vein thrombosis, pulmonary embolism, ischaemic stroke, myocardial infarction), reduction in anti-factor Xa activity, neurosurgical intervention rate, and hospital and ICU length of stay.
Background and Rationale:___Factor Xa inhibitors are among the most commonly prescribed anticoagulants and are widely used in elderly patients with atrial fibrillation and venous thromboembolism. When these patients sustain traumatic brain injury, the ongoing anticoagulant effect significantly increases the risk of haematoma expansion, neurological deterioration, and mortality. Andexanet alfa was developed as a specific reversal agent for FXa inhibitors and gained initial approval following the ANNEXA-4 trial. The ANNEXA-4 final report demonstrated hemostatic efficacy of 82% in patients with intracranial haemorrhage (ICH). [⚠ check for citation marker here] The ANNEXA-I randomised trial subsequently confirmed superiority of andexanet alfa over usual care (predominantly four-factor prothrombin complex concentrate, 4F-PCC) for spontaneous ICH, with a 67.0% versus 53.1% rate of hemostatic efficacy, though it noted a higher rate of thrombotic events in the andexanet group (10.3% versus 5.6%). [⚠ check for citation marker here] Real-world observational studies have yielded variable efficacy rates in mixed ICH populations, ranging from 67% to 83% depending on the cohort and assessment methodology. Systematic reviews and meta-analyses comparing andexanet alfa with 4F-PCC for FXa inhibitor-associated ICH have reported broadly comparable hemostatic efficacy, with some analyses suggesting marginally better haematoma control with andexanet alfa but a potentially higher thrombotic risk. Clinical guidelines acknowledge the limited evidence base for TBI-specific reversal and recognise the need for further data in this population. Notably, several studies have suggested that patients with traumatic ICH on FXa inhibitors may have lower rates of haematoma expansion than spontaneous ICH patients even without specific reversal, raising questions about optimal management strategies. To date, no dedicated study has systematically evaluated andexanet alfa specifically in a TBI cohort using standardised CT-based hemostatic efficacy criteria across all traumatic ICH subtypes (IPH, SDH, EDH, SAH). Study Design:___This is a retrospective observational cohort study conducted at a single tertiary trauma centre. All adult patients (age ≥18 years) admitted with traumatic brain injury (Glasgow Coma Scale 7-15) who were receiving a direct FXa inhibitor (apixaban, rivaroxaban) and who received andexanet alfa for anticoagulation reversal during the study period were identified through pharmacy dispensing records.
1,721 studies on the registry are indexed under Brain Injuries, Traumatic; 447 are open to participants now.
This study's enrollment of 34 is below the median of 117 across 557 observational studies indexed under Brain Injuries, Traumatic.
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Adult patients (age ≥18 years) with traumatic brain injury presenting to a single tertiary trauma centre who were on direct factor Xa inhibitor anticoagulation (apixaban, rivaroxaban) at the time of injury and received andexanet alfa for reversal of anticoagulation. The study population is drawn from consecutive patients treated at the institution during the study period.
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Exclusion Criteria:
Adult patients (age ≥18 years) with traumatic brain injury (Glasgow Coma Scale 7-15) who were receiving a direct factor Xa inhibitor (apixaban, rivaroxaban) at the time of injury and who received andexanet alfa for reversal of anticoagulation following CT-confirmed traumatic intracranial haemorrhage at UMC ljubljana, Slovenia, \[2024-2026\]. All patients had a baseline CT scan performed prior to or shortly after andexanet alfa administration and at least one follow-up CT scan within 24 hours. The cohort includes patients with all subtypes of traumatic intracranial haemorrhage, including intraparenchymal haemorrhage, subdural haematoma, epidural haematoma, subarachnoid haemorrhage, or combinations thereof. Andexanet alfa was dosed according to the product labelling based on the specific FXa inhibitor, dose, and timing of the last dose.
Hemostatic Efficacy
Proportion of patients achieving Excellent or Good hemostatic efficacy on follow-up CT imaging within 24 hours of andexanet alfa administration. Hemostatic efficacy is classified based on the percentage change in haematoma volume (for intraparenchymal haemorrhage) or maximum thickness (for subdural haematoma, epidural haematoma, or subarachnoid haemorrhage) between baseline CT and follow-up CT: * Excellent: ≤20% increase in haematoma volume or thickness * Good: 21-35% increase in haematoma volume or thickness * Poor: \>35% increase in haematoma volume or thickness. For patients with multiple haemorrhage subtypes, the dominant lesion determines classification. This scale is consistent with modified criteria used in the ANNEXA-4 trial
Time frame: Within 24 hours of andexanet alfa administration
All-Cause Mortality during the hospital stay
Proportion of patients who died from any cause within hospital stay
Time frame: From enrollment to the hospital discharge
Thrombotic Complications
Proportion of patients experiencing any thrombotic event within 30 days, including deep vein thrombosis (DVT), pulmonary embolism (PE), ischaemic stroke, and myocardial infarction (MI).
Time frame: Up to 30 days after andexanet alfa administration
Anti-Factor Xa Activity Reduction
Change in anti-factor Xa activity from baseline (pre-bolus) to post-bolus and post-infusion time points, expressed as absolute change and percentage reduction.
Time frame: Up to three days after andexanet application
Hospital Length of Stay
Duration of hospital length of stay, measured in days from admission
Time frame: Up to hospital discharge (estimated up to 90 days after admission)
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is completed, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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