Annexa-S: Trial of Andexanet in Patients Receiving an Oral FXa Inhibitor Who Require Urgent Surgery

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT04233073

Collaborator

(none)

Enrollment

Locations

8.5

Actual Duration (Months)

0.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Prospective, open-label clinical trial to evaluate the efficacy and safety of andexanet alfa patients who require urgent surgery that have been anticoagulated with the FXa (activated factor X) inhibitors.

Condition or Disease	Intervention/Treatment	Phase
Surgery	Drug: andexanet alfa	Phase 2

Detailed Description

This is a multicenter, prospective, open-label study to determine the efficacy and safety of andexanet in patients who require urgent surgery who have received 1 of the following FXa inhibitors: apixaban, rivaroxaban, edoxaban, or enoxaparin. The start of surgery must be within 15 hours following the last dose of FXa inhibitor. The primary efficacy outcome will be adjudicated by an independent Endpoint Adjudication Committee.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Prospective, Open-Label Clinical Study of Andexanet Alfa in Patients Receiving FXa (Activated Factor X) Inhibitor Who Require Urgent Surgery

Actual Study Start Date :

May 11, 2021

Actual Primary Completion Date :

Nov 23, 2021

Actual Study Completion Date :

Jan 25, 2022

Outcome Measures

Primary Outcome Measures

Proportion of patients with good or excellent intraoperative hemostatic efficacy as determined by the surgeon's assessment and confirmed by an independent adjudication committee [At the end of surgery, not to exceed a total of 6.5 hours of andexanet dosing]

Secondary Outcome Measures

Percent change from baseline in anti-fXa activity [At the end of surgery, not to exceed a total of 6.5 hours of andexanet dosing]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 84 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All of the following criteria must be met for the patient to be eligible:

Either the patient or their medical proxy (or legal designee) has given written informed consent.
Age ≥ 18 and < 85 years old.
Requires urgent surgical intervention that must occur within 12 hours of consent, for which reversal of anti-fXa activity is judged necessary.
Treatment with an oral FXa inhibitor (apixaban [last dose 2.5 mg or greater], rivaroxaban [last dose 10 mg or greater], edoxaban [last dose 30 mg or greater] or enoxaparin [≥ 1 mg/kg/d]):
≤ 15 hours prior to start of surgery.
15 hours prior to start of surgery or unknown time from the last dose, if documented anti fXa activity is > 100 ng/mL (> 0.5 IU/mL for enoxaparin, or over the equivalent IU/mL threshold on a low molecular weight heparin assay; see Laboratory Manual) within 2 hours prior to consent. Note: Patients enrolled in this manner should receive a high-andexanet dosing regimen.
Have a negative pregnancy test documented prior to enrollment (for women of childbearing potential).
Willingness to use highly effective methods of contraception through 30 days following study drug dose (for female and male patients who are fertile).

Exclusion Criteria:

If a patient meets any of the following criteria, he or she is not eligible:

Surgery for which the risk of clinically meaningful uncontrolled or unmanageable bleeding is low.
Acute life-threatening bleeding (ISTH criteria) at the time of Screening:

The patient has acute-overt bleeding that is potentially life-threatening, e.g., with signs or symptoms of hemodynamic compromise, such as severe hypotension, poor skin perfusion, mental confusion, low urine output that cannot be otherwise explained.
The patient has overt bleeding associated with a fall in hemoglobin level by ≥2g/dL, OR, a hemoglobin ≤8 g/dL if no baseline hemoglobin is available.
The patient has acute bleeding in a critical area or organ, such as pericardial, intracranial, or intraspinal.

Any surgical procedure that involves the intraoperative use of systemic, intravascular, unfractionated heparin.
Primary procedure for efficacy assessment is a non-surgical interventional procedure (e.g, lumbar puncture, skin biopsy, cardiac catheterization, endoscopic retrograde cholangio-pancreatography).
Expected survival of < 1 month due to comorbidity.
Known "Do Not Resuscitate" order or similar advanced directive.
The patient has a recent history (within 30 days prior to screening) of a diagnosed TE as follows: venous thromboembolism (including deep vein thrombosis, pulmonary embolism, intracardiac thrombus), myocardial infarction (including asymptomatic troponin elevations), disseminated intravascular coagulation, acute traumatic coagulopathy, cerebrovascular accident, transient ischemic attack, unstable angina pectoris hospitalization, or severe peripheral vascular disease.
Acute decompensated heart failure or cardiogenic shock at the time of screening.
The patient has sepsis or septic or severe hemorrhagic shock at the time of Screening.
The patient has heparin-induced thrombocytopenia (with or without thrombosis).
Inherited coagulopathy (e.g., anti-phospholipid antibody syndrome, protein C/S deficiency, Factor V Leiden) at time of Screening.
Platelet count < 80,000/µL at the time of Screening.
Last dose of apixaban < 2.5 mg, rivaroxaban < 10 mg, edoxaban < 30 mg, or enoxaparin 40 mg.
The patient is pregnant or a lactating female.
The patient has received any of the following drugs or blood products within 7 days of enrollment:
Vitamin K antagonists (e.g., warfarin).
Dabigatran.
Prothrombin complex concentrate products (e.g., Kcentra®) or recombinant factor VIIa (e.g., NovoSeven®).
Whole blood, plasma fractions. Note: Administration of tranexamic acid, platelets or packed red blood cells is not an exclusion criterion.
The patient was treated with an investigational drug < 30 days prior to Screening.
Prior treatment with andexanet.
Known hypersensitivity to any component of andexanet.
Known allergic reaction to hamster proteins.
Known or suspected (i.e., presumed positive) COVID-19-related illness at the time of Screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Phoenix	Arizona	United States	85006
2	Clinical Trial Site	Tucson	Arizona	United States	85724
3	Clinical Trial Site	Long Beach	California	United States	90806
4	Clinical Trial Site	Moreno Valley	California	United States	92555
5	Clinical Trial Site	Washington	District of Columbia	United States	20037
6	Clinical Trial Site	Sarasota	Florida	United States	34239
7	Clinical Trial Site	Tampa	Florida	United States	33606
8	Clinical Trial Site	Iowa City	Iowa	United States	52242
9	Clinical Trial Site	Boston	Massachusetts	United States	02111
10	Clinical Trial Site	Boston	Massachusetts	United States	02114
11	Clinical Trial Site	Camden	New Jersey	United States	08103
12	Clinical Trial Site	Staten Island	New York	United States	10305
13	Clinical Trial Site	Charlotte	North Carolina	United States	28203
14	Clinical Trial Site	Durham	North Carolina	United States	27710
15	Clinical Trial Site	Columbus	Ohio	United States	43210
16	Clinical Trial Site	Tulsa	Oklahoma	United States	74104
17	Clinical Trial Site	Portland	Oregon	United States	97239
18	Clinical Trial Site	Philadelphia	Pennsylvania	United States	19104
19	Clinical Trial Site	Pittsburgh	Pennsylvania	United States	15212
20	Clinical Trial Site	Pittsburgh	Pennsylvania	United States	15213
21	Clinical Trial Site	Graz		Austria	8036
22	Clinical Trial Site	Innsbruck		Austria	6020
23	Clinical Trial Site	Klagenfurt am Wörthersee		Austria	9020
24	Clinical Trial Site	Wien		Austria	1090
25	Clinical Trial Site	Clermont-Ferrand		France	63003
26	Clinical Trial Site	Dijon		France	21070
27	Clinical Trial Site	Lille		France	59037
28	Clinical Trial Site	Nantes		France	44093
29	Clinical Trial Site	Paris		France	75012
30	Clinical Trial Site	Paris		France	75679
31	Clinical Trial Site	Aachen		Germany	52074
32	Clinical Trial Site	Bonn		Germany	53127
33	Clinical Trial Site	Dortmund		Germany	44137
34	Clinical Trial Site	Freiburg		Germany	79106
35	Clinical Trial Site	Gießen		Germany	35392
36	Clinical Trial Site	Heidelberg		Germany	69120
37	Clinical Trial Site	Konstanz		Germany	78464
38	Clinical Trial Site	Köln		Germany	51109
39	Clinical Trial Site	Mainz		Germany	55131
40	Clinical Trial Site	Murnau Am Staffelsee		Germany	82418
41	Clinical Trial Site	Würzburg		Germany	97080
42	Clinical Trial Site	Ashkelon		Israel	7830604
43	Clinical Trial Site	Haifa		Israel	3109601
44	Clinical Trial Site	Jerusalem		Israel	9103102
45	Clinical Trial Site	Jerusalem		Israel	92100
46	Clinical Trial Site	Petah Tikva		Israel	4941492
47	Clinical Trial Site	Kamakura		Japan	247-8533
48	Clinical Trial Site	Kasuga		Japan	816-0864
49	Clinical Trial Site	Kawasaki		Japan	216-8511
50	Clinical Trial Site	Kumamoto		Japan	860-0008
51	Clinical Trial Site	Kumamoto		Japan	861-8520
52	Clinical Trial Site	Kurume		Japan	830-8543
53	Clinical Trial Site	Nagoya		Japan	466-8650
54	Clinical Trial Site	Sakai		Japan	593-8304
55	Clinical Trial Site	Sendai		Japan	980-8574
56	Clinical Trial Site	Tokyo		Japan	113-8602