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

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-NL
• 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: 2022-04-25
• Last Update Posted: 8 April 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 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.
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 460
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

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 26 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. 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.

Study & Design

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