Trial Outcomes & Findings for Trial of Andexanet in Patients Receiving an Oral FXa Inhibitor Who Require Urgent Surgery (NCT NCT04233073)

Last Updated: 2023-03-22

Results Overview

Effective hemostasis is defined as excellent or good as assessed by the Investigator; Ineffective hemostasis is defined as moderate or poor as assessed by the Investigator. All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Hemostasis will be assessed from the start of surgery to the end of the procedure

Results posted on

2023-03-22

Participant Flow

Participants who required urgent surgery and received factor Xa (fXa) inhibitors (apixaban, rivaroxaban, edoxaban, or enoxaparin) before surgery were enrolled in the study.

This study is a single-arm study and all participants received 1 of 2 doses of andexanet based on the specific anticoagulant taken. All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.

Participant milestones

Participant milestones
Measure	Andexanet Alfa Participants received a dose of andexanet alfa based on the specific FXa inhibitor, dose, and time since the last dose (\<8 hours, ≥8 hours, or unknown).
Overall Study STARTED	10
Overall Study Treated With Any Amount of Andexanet	10
Overall Study Efficacy Set	6
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Andexanet Alfa Participants received a dose of andexanet alfa based on the specific FXa inhibitor, dose, and time since the last dose (\<8 hours, ≥8 hours, or unknown).
Overall Study Death	5

Baseline Characteristics

Per local law, ethnicity data not collected for participants located in France.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Andexanet Alfa n=10 Participants Participants received a dose of andexanet alfa based on the specific FXa inhibitor, dose, and time since the last dose (\<8 hours, ≥8 hours, or unknown).
Age, Continuous	79.8 Years n=10 Participants
Sex: Female, Male Female	7 Participants n=10 Participants
Sex: Female, Male Male	3 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.
Race (NIH/OMB) Asian	0 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.
Race (NIH/OMB) Black or African American	0 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.
Race (NIH/OMB) White	6 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.
Race (NIH/OMB) More than one race	0 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants • Per local law, ethnicity data not collected for participants located in France.

PRIMARY outcome

Timeframe: Hemostasis will be assessed from the start of surgery to the end of the procedure

Population: Efficacy Set: Participants who underwent surgery and had a baseline anti-fXa activity of at least 75 nanograms (ng)/milliliter (mL) for participants receiving apixaban or rivaroxaban, 40 ng/mL for participants receiving edoxaban, and 0.25 international units (IU)/mL for participants on enoxaparin. All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.

Outcome measures

Outcome measures
Measure	Andexanet Alfa n=6 Participants Participants received a dose of andexanet alfa based on the specific FXa inhibitor, dose, and time since the last dose (\<8 hours, ≥8 hours, or unknown).
Number of Participants Achieving Effective Hemostasis	6 Participants

SECONDARY outcome

Timeframe: Baseline, Treatment nadir (not to exceed a total of 6.5 hours of andexanet dosing)

Population: Efficacy Set: Participants who underwent surgery and had a baseline anti-fXa activity of at least 75 ng/mL for participants receiving apixaban or rivaroxaban, 40 ng/mL for participants receiving edoxaban, and 0.25 IU/mL for participants on enoxaparin. All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.

Baseline is defined as the last non-missing value on or before first study drug administration. On treatment nadir is the minimum value of anti-fXa activity during the period of time from the end of the andexanet bolus to the end of the andexanet infusion. All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.

Outcome measures

Outcome measures
Measure	Andexanet Alfa n=6 Participants Participants received a dose of andexanet alfa based on the specific FXa inhibitor, dose, and time since the last dose (\<8 hours, ≥8 hours, or unknown).
Percent Change From Baseline In Anti-fXa Activity To Treatment Nadir	-96.13 Percent Change Interval -97.4 to -89.2

Adverse Events

Andexanet Alfa

Serious events: 7 serious events

Other events: 2 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Andexanet Alfa n=10 participants at risk Participants received a dose of andexanet alfa based on the specific FXa inhibitor, dose, and time since the last dose (\<8 hours, ≥8 hours, or unknown).
Cardiac disorders Stress cardiomyopathy	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Injury, poisoning and procedural complications Periprosthetic fracture	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Injury, poisoning and procedural complications Postprocedural hematoma	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Nervous system disorders Ischaemic stroke	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Renal and urinary disorders Acute kidney injury	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Vascular disorders Thrombosis	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.

Other adverse events

Other adverse events
Measure	Andexanet Alfa n=10 participants at risk Participants received a dose of andexanet alfa based on the specific FXa inhibitor, dose, and time since the last dose (\<8 hours, ≥8 hours, or unknown).
Blood and lymphatic system disorders Anaemia	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Metabolism and nutrition disorders Vitamin B complex deficiency	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Renal and urinary disorders Acute kidney injury	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Metabolism and nutrition disorders Vitamin D deficiency	10.0% 1/10 • Number of events 1 • Day 1 up to Day 37 All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.

Additional Information

Alexion Pharmaceuticals, Inc.

Phone: +1-855-752-2356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place