Coagulation Disorder
Conditions
Keywords
Reversal of Factor Xa inhibitors
Brief summary
The aim of this study is to find out the effects of TAK-330 compared with four-factor prothrombin complex concentrate (4F-PCC) as part of standard treatment other than Prothromplex Total for anticoagulation reversal in participants treated with Factor Xa inhibitors who require urgent surgery/invasive procedure. The participant will be assigned by chance to either TAK-330 or SOC 4F-PCC as part of standard treatment before surgery. Patients participating in this study will need to be hospitalized. They will also be contacted (via telehealth/phone call) 30 days after the surgery.
Interventions
DRUGTAK-330
Participants will receive TAK-330, 25 IU/kg single intravenous infusion on Day 1 and an additional dose of 25 IU/kg TAK-330 can be administered if required.
DRUGSOC 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 total dose of 50 IU/kg or 5,000 IU, whichever is smaller can be given during the surgery if required.
Sponsors
Takeda
Takeda Development Center Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Adaptive parallel-group sequential design.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 that is associated with high-risk of intraoperative bleeding 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. For participants who are beyond the 15-hour window, eligibility requires proof of elevated plasma anti-Factor Xa (FXa) levels using either specific direct oral anti-coagulant (DOAC)-calibrated (apixaban, rivaroxaban or edoxaban) anti-FXa levels of greater than (\>) 75 nanograms per milliliter (ng/mL), or heparin calibrated anti-FXa assay levels of \>0.5 international unit per milliliter (IU/mL) at screening. * 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 prior to screening) of venous thromboembolism, myocardial infarction (MI), disseminated intravascular coagulation (DIC), ischemic stroke, transient ischemic attack, hospitalization for unstable angina pectoris or severe or critical coronavirus 2 (SARS-CoV-2) infection. * Active major bleeding defined as bleeding that requires surgery or transfusion of \>2 units of packed red blood cell (PRBC) or intracranial hemorrhage with the exception of subacute and chronic subdural hemorrhages with a Glasgow Coma Score (GCS) greater than or equal to (\>=) 9. * Polytrauma 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 (example, platelet function disorders, hemophilia, Von Willebrand disease, or coagulation factor deficiency). * Platelet count less than (\<) 50,000 per microliter (/mcL). * History of heparin-induced thrombocytopenia. * Administration of procoagulant drugs (example, 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Intraoperative Effective Hemostasis | At the end of the surgery/procedure | Percentage of participants achieving intraoperative effective hemostasis, as determined by the Intraoperative Four Point Hemostatic Efficacy Scale and assessed by the principal investigator (PI), the surgeon, or a qualified member of the surgical team. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Postoperative Effective Hemostasis | At 24 hours after the end of investigational product infusion | Percentage of participants achieving postoperative effective hemostasis at 24±4 hours following the completion of investigational product infusion, as determined by the Postoperative Four Point Hemostatic Efficacy Scale and assessed by the PI, the surgeon, or a qualified member of the surgical team. |
| Percentage of Participants With Intraoperative Effective Hemostasis Based on Hemostatic Efficacy Rating Algorithm | At the end of the surgery/procedure | Percentage of participants achieving intraoperative effective hemostasis, as determined by the Hemostatic Efficacy Rating Algorithm and assessed by the PI, the surgeon, or a qualified member of the surgical team. |
| 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 end 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 are 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 and hypercoagulability. |
| 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. |
Countries
Argentina, Austria, Belgium, Brazil, Canada, Czechia, France, Germany, Greece, Hungary, Israel, Poland, Portugal, Spain, United States
Contacts
CONTACTTakeda Contact
STUDY_DIRECTORStudy Director
Takeda
Outcome results
None listed