Phase 3 Trial of TAK-330 for Reversal of Direct Oral Factor Xa Inhibitor-induced Anticoagulatio

Phase 1

• Conditions: Patients on treatment with Factor Xa Inhibitor needing for an urgent intervention associated with a high risk of bleeding.; MedDRA version: 20.0Level: LLTClassification code 10075279Term: Anticoagulant reversal therapySystem Organ Class: 100000004865; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2021-004138-12-AT
• Lead Sponsor: Takeda Development Center Americas, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-04-19
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

1. Subject or legally authorized representative willing to sign e-consent/written informed consent form.
2. Subjects =18 years of age at enrollment.
3. Subject currently on treatment with oral Factor Xa inhibitor (rivaroxaban, apixaban, edoxaban).
4. In the opinion of the surgeon, the subject requires urgent surgery/procedure that is associated with high-risk of intraoperative bleeding within 15 hours of the last Factor Xa inhibitor dose and requiresa reversal agent for suspected direct oral Factor Xa inhibitor-related coagulopathy.
5. Women of childbearing potential should have a negative pregnancy test documented prior to enrollment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. The subject has an expected survival of less than 30 days, even with best available medical and surgical care.
2. Recent history (within 90 days prior to screening) of venous thromboembolism, myocardial infarction (MI), DIC, ischemic stroke,
transient ischemic attack, hospitalization for unstable angina pectoris or severe or critical coronavirus 2 (SARS-CoV-2) infection.
3. Acute major bleeding defined as bleeding that requires surgery or transfusion of >2 units of PRBC or intracranial hemorrhage.
4. Polytrauma for which reversal of Factor Xa-inhibition alone would not be sufficient to achieve hemostasis.
5. Known prothrombotic disorder including primary antiphospholipid syndrome, antithrombin-3 deficiency, homozygous protein C deficiency, homozygous protein S deficiency, and homozygous factor V Leiden.
6. Known bleeding disorder (eg, platelet function disorder, hemophilia, Von Willebrand disease, or coagulation factor deficiency).
7. Platelet count <100,000/µL.
8. History of heparin-induced thrombocytopenia.
9. Administration of procoagulant drugs (eg, Vitamin K, non-study prothrombin complex concentrates (PCCs), recombinant Factor VIIa, tranexamic acid) or blood products (transfusion of whole blood, fresh frozen plasma, cryoglobulins, plasma fractions, or platelets) within 7 days before enrollment. (Note: administration of PRBCs for hemoglobin correction is not an exclusion criterion).
10. Planned use of procoagulant drugs (eg, Vitamin K, non-study PCCs, recombinant Factor VIIa, tranexamic acid) or blood products (transfusion of whole blood, fresh frozen plasma, cryoglobulins, plasma fractions, or platelets) after enrollment but before the investigational product infusion is initiated (Note: administration of PRBCs for hemoglobin correction is not an exclusion criterion).
11. Administration of unfractionated or low molecular weight heparin within 24 hours before randomization.
12. Hypersensitivity to PCC constituents, or any excipient of TAK-330.
13. Patients with history of confirmed immunoglobulin A (IgA)
deficiency with hypersensitivity reaction and antibodies to IgA.
14. Suspected sepsis as defined by infection associated with two of the
following three criteria: Respiratory rate = 22, systolic blood pressure =
100 mmHg, and Glasgow Coma Score < 15.
15. Acute or chronic liver failure (hepatic cirrhosis Child-PUGH score C).
16. Renal failure requiring dialysis.
17. Any other condition that could, in the opinion of the investigator, put
the subject at undue risk of harm if the subject were to participate in the
study.
18. Participation in another clinical study involving an investigational
product or device within 30 days prior to study enrollment, or planned
participation in another clinical study involving an investigational
product or device during the course of this study.
19. The use of PROTHROMPLEX TOTAL as SOC 4F-PCC.
20. Women who are breastfeeding at the time of enrollment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate intraoperative efficacy of PROTHROMPLEX TOTAL in comparison with standard of care (SOC) 4-factor prothrombin complex concentrate (4F-PCC), for reversal of anticoagulation in patients receiving direct oral Factor Xa inhibitors and requiring urgent surgery/invasive procedure within 15 hours from the last dose of Factor Xa inhibitor.;Secondary Objective: To assess the safety and postoperative efficacy of PROTHROMPLEX TOTAL in comparison with SOC 4F-PCC, for reversal of anticoagulation in patients receiving direct oral Factor Xa inhibitors and requiring urgent surgery/invasive procedure within 15 hours of the last dose of Factor Xa inhibitor.;Primary end point(s): Occurrence of intraoperative effective hemostasis based on the surgeon's assessment at the end of the<br>surgery/invasive procedure using the Four Point Intraoperative Hemostatic Efficacy Scale.;Timepoint(s) of evaluation of this end point: End of the surgery