A Study of Andexanet Alfa in Patients Requiring Urgent Surgery or Procedure

Urgent Surgery Clinical Trial

— ANNEXA-RS  

Official title:

A Randomized Study of Andexanet Alfa Compared to Usual Care in Patients Receiving a Factor Xa Inhibitor Who Require Urgent Surgery or Procedure (ANNEXA-RS)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05926349
• Other study ID #: D9604C00001
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 20, 2023
• Est. completion date: November 24, 2026

Study information

• Verified date: September 2023
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will aim to find out if the drug andexanet alfa is safe and effective in preventing major bleeding during urgent surgery or invasive procedures. The study will compare the use of andexanet alfa to the usual care given at the study center.

Description:

This study will be an open-label, randomised, controlled, prospective, multicenter study. The study will include patients requiring urgent surgery or procedure that needs to be performed within 15 hours of the last dose of blood-thinning drug (direct oral activated Factor X (FXa) inhibitor).

The study will comprise of the following periods:

• Screening, followed by surgery or procedure and study intervention.

• Follow-up period: there will be four follow-up visits over a duration of approximately 30 days.

• Follow-up visit for patients with positive anti-andexanet alfa antibody test: patients with a positive anti-andexanet alfa antibody response at day 30 will have a follow-up anti-andexanet alfa antibody test approximately 120 days post-surgery or procedure.

Patients will be randomised in the ratio of 1:1 to receive either andexanet alfa or usual care.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 800
• Est. completion date: November 24, 2026
• Est. primary completion date: November 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• The patient requires, in the opinion of the Investigator, urgent surgery or procedure and requires reversal of direct oral FXa inhibition.

• The patient requires urgent surgery or procedure within 12 hours of informed consent.

• The patient requires urgent surgery or procedure that is expected to be associated with a high risk of bleeding or bleeding to occur into a critical organ.

• The patient has taken an oral FXa inhibitor (such as apixaban, rivaroxaban, or edoxaban) within 15 hours or more, prior to start of surgery or procedure.

• Female patients of childbearing potential must have a negative pregnancy test at Screening.

• Willingness to use highly effective methods of contraception (for male and female patients who are fertile).

Exclusion Criteria:

• The patient requires surgeries or procedures that have a very low chance of causing significant, uncontrollable bleeding, such as small skin procedures, cataract surgery, and minor dental procedures.

• The patient has acute life-threatening bleeding at the time of Screening.

• The patient will undergo a surgery or procedure which will require the use of heparin.

• Patient who is not expected to live for more than three months due to other health problems or has specifically requested not to be resuscitated if their heart stops beating.

• Prior to screening, the patient had either experienced low platelet count due to heparin use with or without blood clots or had a genetic condition that affects blood clotting.

• Patient has acute decompensated heart failure, cardiogenic shock, sepsis, or septic shock at the time of Screening.

• Patient has history of heparin-induced thrombocytopenia (with or without thrombosis) or inherited coagulopathy (eg, anti-thrombin III deficiency, anti-phospholipid antibody syndrome, protein C/S deficiency, Factor V Leiden) at the time of Screening.

• Previously diagnosed with a bleeding disorder (eg, platelet function disorder, hemophilia, Von Willebrand disease, or coagulation factor deficiency).

• Prior known hypersensitivity to andexanet alfa.

• Use of andexanet alfa 30 days prior to Screening.

• Patient diagnosed with dementia.

• Any prohibited medication as determined in the study.

Related Conditions & MeSH terms

• Urgent Surgery

Intervention

Drug:
• Andexanet alfa
Andexanet is a recombinant version of human FXa
• Usual Care
As per the label of the chosen usual care product(s) and/or usual care standards.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Córdoba
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Quilmes
Australia	Research Site	Adelaide
Australia	Research Site	Concord
Australia	Research Site	Epping
Australia	Research Site	Fitzroy
Australia	Research Site	Garran
Australia	Research Site	Melbourne
Australia	Research Site	New Lambton Heights
Australia	Research Site	Sydney
Austria	Research Site	Graz
Belgium	Research Site	Aalst
Belgium	Research Site	Ghent
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Brazil	Research Site	Florianopolis
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Paulo
Bulgaria	Research Site	Lom
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Canada	Research Site	Montreal	Quebec
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Haerbin
China	Research Site	Hangzhou
China	Research Site	Wuhan
Czechia	Research Site	Brno
Czechia	Research Site	Prague
Czechia	Research Site	Praha 10
Czechia	Research Site	Usti nad Labem
Denmark	Research Site	København NV
Estonia	Research Site	Tallinn
Finland	Research Site	Helsinki
Finland	Research Site	Tampere
France	Research Site	Nantes cedex 1
France	Research Site	Nimes
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Germany	Research Site	Aachen
Germany	Research Site	Dresden
Germany	Research Site	Lübeck
Germany	Research Site	Mainz
Germany	Research Site	Murnau
Germany	Research Site	Rostock
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
Hungary	Research Site	Budapest
Hungary	Research Site	Pécs
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Zalaegerszeg
Israel	Research Site	Ashdod
Israel	Research Site	Jerusalem
Israel	Research Site	Petah Tikva
Israel	Research Site	Tel-Aviv
Italy	Research Site	Alessandria
Italy	Research Site	Catania
Italy	Research Site	Milano
Italy	Research Site	Parma
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Varese
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kashihara-shi
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kurume
Japan	Research Site	Sakai-shi
Japan	Research Site	Sendai-shi
Korea, Republic of	Research Site	Daegu
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuantan
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Nuevo Leon
Mexico	Research Site	San Luis Río Colorado
New Zealand	Research Site	Auckland
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Szczecin
Portugal	Research Site	Amadora
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Timisoara
Serbia	Research Site	Kragujevac
Serbia	Research Site	Nis
Serbia	Research Site	Novi Sad
Serbia	Research Site	Sremska Kamenica
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Slovakia	Research Site	Bratislava
Slovenia	Research Site	Celje
Spain	Research Site	Barcelona
Spain	Research Site	Elche
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Marbella (Málaga)
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Switzerland	Research Site	Zurich
Taiwan	Research Site	Tainan
United Kingdom	Research Site	London
United States	Research Site	Aurora	Colorado
United States	Research Site	Chandler	Arizona
United States	Research Site	Columbus	Ohio
United States	Research Site	Jacksonville	Florida
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Saint Cloud	Florida
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Denmark,  Estonia,  Finland,  France,  Georgia,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  New Zealand,  Poland,  Portugal,  Romania,  Serbia,  Singapore,  Slovakia,  Slovenia,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients with adverse events	Safety and tolerability will be evaluated in terms of adverse events and serious adverse events.	Screening (Day -1 to Day 0) until follow-up visit (Day 30 or Day 120)
Primary	Number of patients achieving effective intraoperative hemostasis	Intraoperative hemostasis will be assessed according to the categories as per 4-point hemostasis scale: Excellent - Normal hemostasis, Good - Mildly abnormal hemostasis (eg. slight oozing from surgical wounds), Moderate - Moderate abnormality in intraprocedural hemostasis (eg. controllable bleeding), Poor - Severe hemostatic abnormality (eg. severe refractory hemorrhage). Hemostasis will be considered to be effective if the intraoperative hemostasis category is 'excellent' or 'good', and ineffective if the intraoperative hemostasis category is 'moderate' or 'poor'.	From start to the end of surgery or procedure on Day 0
Secondary	Change from Baseline in anti-FXa activity measured through blood samples	The ability of andexanet alfa to rapidly reverse the anticoagulation effect of FXa inhibitors by reduction of anti-FXa activity when compared to usual care.	Baseline to start of surgery or procedure
Secondary	Change from Baseline in anti-FXa activity measured through blood samples	The ability of andexanet alfa to sustainably reverse the anticoagulation effect of FXa inhibitors by reduction of anti-FXa activity when compared to usual care at two hours post start of surgery or procedure will be assessed.	Baseline to two hours post start of surgery or procedure