A Trial of PROTHROMPLEX TOTAL for Reversal of Direct Oral Factor Xa Inhibitor-induced Anticoagulation
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PROTHROMPLEX TOTAL 25 IU/kg Participants will receive PROTHROMPLEX TOTAL 25 international unit per kilogram (IU/kg) single intravenous infusion on Day 1 (prior to surgery) as an initial dose and an additional dose of 25 international unit per kilogram (IU/kg). PROTHROMPLEX TOTAL can be administered during the surgery if deemed necessary by the surgeon. The total dose of PROTHROMPLEX TOTAL administered to the participant should not exceed 50 IU/kg or 5,000 IU, whichever is smaller. |
Drug: PROTHROMPLEX TOTAL
Participants will receive PROTHROMPLEX TOTAL 25 IU/kg single intravenous infusion on Day 1 and an additional dose of 25 IU/kg PROTHROMPLEX TOTAL can be administered if required.
|
| Active Comparator: 4F-PCC Participants will receive 4F-PCC (excluding prothromplex total and activated 4F-PCC) as SOC on Day 1 (prior to surgery). The dose and infusion speed of the SOC 4F-PCC will be based on local institutional protocols. An additional dose of SOC 4F-PCC not exceeding label specified limits can be given during the surgery if required. |
Drug: 4F-PCC
Participants will receive 4F-PCC as SOC on Day 1. The dose and infusion speed of the SOC 4F-PCC will be based on local institutional protocols. An additional dose of SOC 4F-PCC not exceeding label specified limits can be given during the surgery if required.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Intraoperative Effective Hemostasis [At the end of the surgery/procedure]
Percentage of participants with intraoperative effective hemostasis using Intraoperative Four Point Hemostatic Efficacy Scale that incorporates the surgeon's subjective opinion as to whether intraoperative hemostasis is sufficient and if there is the need for administration of non-study hemostatic treatments will be reported.
Secondary Outcome Measures
- Percentage of Participants With Postoperative Effective Hemostasis [At 24 hours after the end of investigational product infusion]
Percentage of participants with postoperative effective hemostasis using Postoperative Four Point Hemostatic Efficacy Scale based on the surgeon's assessment at 24 hours after the end of investigational product infusion will be reported.
- Percentage of Participants With Intraoperative Effective Hemostasis Based on Hemostatic Efficacy Rating Algorithm [At the end of the surgery/procedure]
Percentage of participants with intraoperative effective hemostasis based on hemostatic efficacy rating algorithm will be reported. The hemostatic efficacy rating (composite) algorithm incorporates the difference between predicted and actual bleeding during surgery, the surgeon's subjective opinion as to whether intraoperative hemostasis is sufficient, and the need for administration of non-study hemostatic treatments.
- Number of Participants With Usage of Blood Products or Non-Study Hemostatic Agents for Bleeding Control [Within 24 hours after the end of investigational product infusion]
Number of participants with usage of blood products or non-study hemostatic agents for bleeding control will be documented from the end of IP infusion to 24 hours after start of study product infusion.
- Number of Units of Packed red Blood Cells (PRBCs) Administered to Achieve Bleeding Control [Within 24 hours after the end of investigational product infusion]
Number of units of PRBCs administered to achieve bleeding control within 24 hours after the end of IP infusion.
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interests (AESIs) [Within 30 days after the end of the surgery/invasive procedure (up to 33 days)]
An Adverse Event (AE) is defined as any untoward medical occurrence (including a symptom or disease or an abnormal laboratory finding) in a participant or clinical investigation participants administered a medicinal product and which does not necessarily have a causal relationship with the treatment. TEAEs is defined as those with a start date on or after the first dose of study treatment, or with a start date before the date of first dose of study treatment but increasing in severity after the first dose of study treatment. A SAE is any event that results in: death; life-threatening event; requires inpatient hospitalization or results in prolongation of existing hospitalization; persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or a medically important event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI.
- Number of Participants With Thrombotic Events [Within 30 days after the end of the surgery/invasive procedure (up to 33 days)]
Number of thrombotic events within 30 days after the end of the surgery/invasive procedure will be assessed. Thrombotic events occur when a blood clot, known as a thrombus, is formed within a blood vessel. It prevents blood from flowing normally through the circulatory system.
- Number of Participants With Deaths Within 30 Days Post-Surgery/Invasive Procedure [Within 30 days post-surgery/invasive procedure (up to 33 days)]
Number of deaths Within 30 days post-surgery/invasive procedure will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant or legally authorized representative willing to sign e-consent/written informed consent form.
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Participants at least 18 years of age at enrollment.
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Participant currently on treatment with oral Factor Xa inhibitor (rivaroxaban, apixaban, edoxaban).
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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.
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Women of childbearing potential should have a negative pregnancy test documented prior to enrollment.
Exclusion Criteria:
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The participant has an expected survival of less than 30 days, even with best available medical and surgical care.
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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.
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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.
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Acute trauma for which reversal of Factor Xa-inhibition alone would not be sufficient to achieve hemostasis.
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Known prothrombotic disorder including primary antiphospholipid syndrome, antithrombin-3 deficiency, homozygous protein C deficiency, homozygous protein S deficiency, and homozygous factor V Leiden.
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Known bleeding disorder (eg, platelet function disorder, hemophilia, Von Willebrand disease, or coagulation factor deficiency).
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Platelet count less than (<) 100,000 per microliter (/mcL).
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History of heparin-induced thrombocytopenia.
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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).
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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).
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Administration of unfractionated or low molecular weight heparin within 24 hours before randomization.
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Hypersensitivity to PCC constituents or any excipient of PROTHROMPLEX TOTAL
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Confirmed or suspected sepsis.
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Acute or chronic liver failure (hepatic cirrhosis Child-PUGH score C)
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Renal failure requiring dialysis
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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.
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Takeda
- Takeda Development Center Americas, Inc.
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- TAK-330-3001
- 2021-004138-12