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)

Alexion Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Bleeding

Treatments: Biological: Andexanet

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02329327

14-505

Details and patient eligibility

About

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.

Enrollment: 479 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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479 participants in 1 patient group

Andexanet

Experimental group

Description:

Participants received andexanet as an intravenous bolus administered over \~15 to 30 minutes, followed immediately by a continuous infusion administered over \~120 minutes.

Treatment:

Biological: Andexanet