A Trial of PROTHROMPLEX TOTAL for Reversal of Direct Oral Factor Xa Inhibitor-induced Anticoagulation

• Status: Not yet recruiting
• Trial end date: 2023-06-30
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to examine the potential of PROTHROMPLEX TOTAL compared to investigator-assigned four-factor prothrombin complex concentrate (4F-PCC) as a part of SOC for the reversal of anticoagulation in participants treated with Factor Xa inhibitors who require urgent surgery/invasive procedure.

The participant will be randomized to PROTHROMPLEX TOTAL or investigator-assigned 4F-PCC as a part of SOC prior to surgery.

Patients participating in this study will need to be hospitalized. They will also be contacted (via telehealth/remote monitoring) 30 days after the surgery.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Takeda
• Collaborator: Takeda Development Center Americas, Inc.

Criteria

Inclusion Criteria:

• Participant or legally authorized representative willing to sign e-consent/written informed consent form.

• Participants at least 18 years of age at enrollment.

• Participant currently on treatment with oral Factor Xa inhibitor (rivaroxaban, apixaban, edoxaban).

• In the opinion of the surgeon, the participant requires an urgent surgery/procedure within 15 hours from the last dose of Factor Xa inhibitor and requires a reversal agent for suspected direct oral Factor Xa inhibitor-related coagulopathy.

• Women of childbearing potential should have a negative pregnancy test documented prior to enrollment.

Exclusion Criteria:

• The participant has an expected survival of less than 30 days, even with best available medical and surgical care.

• Recent history (within 90 days before screening) of venous thromboembolism, myocardial infarction, disseminated intravascular coagulation, ischemic stroke, transient ischemic attack, hospitalization for unstable angina pectoris, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, or severe peripheral vascular disease.

• Acute major bleeding, defined as bleeding that requires surgery or transfusion of greater than or equal (>=) to 2 units of packed red blood cells (PRBCs) or is associated with a decrease in hemoglobin of >= to 1 grams per deciliter (g/L), or intracranial hemorrhage.

• Acute trauma for which reversal of Factor Xa-inhibition alone would not be sufficient to achieve hemostasis.

• Known prothrombotic disorder including primary antiphospholipid syndrome, antithrombin-3 deficiency, homozygous protein C deficiency, homozygous protein S deficiency, and homozygous factor V Leiden.

• Known bleeding disorder (eg, platelet function disorder, hemophilia, Von Willebrand disease, or coagulation factor deficiency).

• Platelet count less than (<) 100,000 per microliter (/mcL).

• History of heparin-induced thrombocytopenia.

• 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).

• 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).

• Administration of unfractionated or low molecular weight heparin within 24 hours before randomization.

• Hypersensitivity to PCC constituents or any excipient of PROTHROMPLEX TOTAL

• Confirmed or suspected sepsis.

• Acute or chronic liver failure (hepatic cirrhosis Child-PUGH score C)

• Renal failure requiring dialysis

• Any other condition that could, in the opinion of the investigator, put the subject at undue risk of harm if the participant were to participate in the study.

• 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.