A Study in Participants With Acute Major Bleeding to Evaluate the Ability of Andexanet Alfa to Reverse the Anticoagulation Effect of Direct and Indirect Oral Anticoagulants (Extension Study)
Condition: Bleeding
MeSH terms: Hemorrhage
Intervention: Andexanet
Intervention description: There were 2 possible dosing regimens: Low dose = 400 milligram (mg) bolus plus 4 mg/minute continuous infusion for 120 minutes; High dose = 800 mg bolus plus 8 mg/minute continuous infusion for 120 minutes.
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 479.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Factor Xa Inhibitors; Major; Bleeding; Anticoagulant; Major Bleeding; Andexanet Alfa; Reversal Agent

Summary:

      The purpose of this study was to evaluate the hemostatic efficacy of andexanet alfa
      (andexanet) in participants receiving a factor Xa (FXa) inhibitor (apixaban, rivaroxaban,
      edoxaban, enoxaparin) who were experiencing an acute major bleed. The safety of andexanet was
      also studied.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Acute major bleeding episode that required urgent reversal of anticoagulation; defined
             by at least one of the following:

               -  Acute bleeding that was potentially life-threatening, or

               -  Acute bleeding associated with a fall in hemoglobin level by ≥2 grams/deciliter
                  (g/dL), or

               -  Acute bleeding associated with a hemoglobin level of ≤8 g/dL if no baseline
                  hemoglobin was available, or

               -  Acute bleeding in a critical area or organ such as intraspinal, pericardial, or
                  intracranial.

          2. If bleeding was intracranial or intraspinal, the participant must have undergone a
             head computed tomography (CT) or magnetic resonance imaging (MRI) scan demonstrating
             the bleeding.

          3. Participant received or was believed to have received one of the following within 18
             hours prior to andexanet administration: apixaban, rivaroxaban, edoxaban, or
             enoxaparin.

          4. For participants with intracranial bleeding, there must be a reasonable expectation
             that andexanet treatment will commence within 2 hours of the baseline imaging
             evaluation.

        Key Exclusion Criteria:

          1. The participant was scheduled to undergo surgery in less than 12 hours, with the
             exception of minimally invasive surgery/procedures.

          2. Participant with an intracerebral hemorrhage that had any of the following:

               -  Glasgow coma score <7, or

               -  Intracerebral hematoma >60 cubic centimeters as assessed by CT or MRI

          3. Participants with visible, musculoskeletal or intra-articular bleeding as their
             qualifying bleed.

          4. Expected survival of less than 1 month.

          5. Recent history (within 2 weeks) of a diagnosed thrombotic event as follows: venous
             thromboembolism, myocardial infarction, disseminated intravascular coagulation,
             cerebral vascular accident, transient ischemic attack, unstable angina pectoris
             hospitalization or severe peripheral vascular disease within 2 weeks prior to
             Screening.

          6. Severe sepsis or septic shock at the time of Screening.

          7. Pregnant or a lactating female.

          8. Participant received any of the following drugs or blood products within 7 days of
             Screening:

               -  Vitamin K antagonist

               -  Dabigatran

               -  Prothrombin Complex Concentrate (PCC) products or recombinant factor VIIa
                  (rfVIIa)

               -  Whole blood, plasma fractions

          9. Treated with an investigational drug <30 days prior to Screening.

         10. Planned administration of PCC, fresh frozen plasma or rfVIIa from Screening until
             within 12 hours after the end of the andexanet infusion.