A Phase 3, Prospective, Randomized, Open-label, Adaptive Group Sequential, Multicenter Trial with Blinded Endpoint Assessment to Evaluate the Efficacy and Safety of TAK-330 for the Reversal of Direct Oral Factor Xa Inhibitor-induced Anticoagulation in Patients Requiring Urgent Surgery/Invasive Procedure

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 35

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 requires a reversal agent for suspected
direct oral Factor Xa inhibitor-related coagulopathy. In subjects who are
beyond the 15-hour window,
eligibility requires proof of elevated plasma anti FXa levels using either
specific DOAC-calibrated (apixaban, rivaroxaban or edoxaban) anti-FXa
levels of > 75ng/mL, or heparin-calibrated anti-FXa assay levels of > 0.5
IU/mL at screening.
5. Women of childbearing potential should have a negative pregnancy test
documented prior to enrollment.

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. Active major bleeding defined as bleeding that requires surgery or
transfusion of >2 units of PRBC or intracranial hemorrhage with the
exception of subacute and chronic subdural hemorrhages with a Glasgow
Coma Score (GCS) >= 9
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 <50,000/µL.
8. History of heparin-induced thrombocytopenia.
9. Administration of procoagulant drugs (eg, non-study prothrombin complex
concentrates (PCCs), recombinant Factor VIIa) 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,
tranexamic acid or aminocaproic acid are not exclusion criteria).
10. Planned use of procoagulant drugs (eg, Vitamin K, non-study PCCs,
recombinant Factor VIIa) 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 tranexamic
acid or aminocaproic acid are not exclusion criteria)
11. Administration of unfractionated heparin within 2 hours before
randomization or low molecular weight heparin within 26hours 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. Septic shock as defined by persistent hypotension requiring
vasopressors to maintain mean arterial pressure (MAP) >= 65mmHg and
having blood lactate > 2 mmol despite adequate volume resuscitation.
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.