A Study of TAK-330 to Reverse the Effects of Factor Xa Inhibitors For Adults Needing Urgent Surgery
Purpose
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.
Condition
- Coagulation Disorder
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts 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 exclusion criteria). - Planned use of procoagulant drugs (example, 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 24±4 hours hemostatic assessment (Key secondary endpoint). Planned administration of tranexamic acid (TXA) or aminocaproic acid after randomization but before the start of IP infusion, should be noted during randomization to properly stratify these participants in the interactive response technology (IRT). Planned administration of TXA or aminocaproic acid after start of IP infusion but before the 24±4 hours hemostatic assessment is prohibited. Administration of any of the above products before the 24±4 hours hemostatic assessment will impact the assessment of hemostasis. Administration of PRBCs for hemoglobin correction, is not an exclusion criterion. - Administration of unfractionated heparin within 2 hours before randomization or low molecular weight heparin within 6 hours before randomization. - Hypersensitivity to PCC constituents or any excipient of TAK-330. - Participants with history of confirmed immunoglobulin A (IgA) deficiency with hypersensitivity reaction and antibodies to IgA. - Septic shock as defined by persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP) >=65 millimeters of mercury (mmHg) and having blood lactate >2 millimole (mmol) despite adequate volume resuscitation. - 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 participant 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. Participation in an observational study is not an exclusion criterion. - The use of PROTHROMPLEX TOTAL as SOC 4F-PCC. - Women who are breastfeeding at the time of enrollment.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Adaptive parallel-group sequential design.
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental TAK-330 25 IU/kg |
Participants will receive TAK-330, 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 IU/kg TAK-330 can be administered during the surgery if deemed necessary by the surgeon. The total dose of TAK-330 administered to the participant should not exceed 50 IU/kg or 5,000 IU, whichever is smaller. |
|
|
Active Comparator SOC 4F-PCC |
Participants will receive 4F-PCC (excluding Prothromplex Total and activated 4F-PCC) as standard of care (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 total dose of 50 IU/kg or 5,000 IU, whichever is smaller can be given during the surgery if required. |
|
Recruiting Locations
University of California Davis Health System
Sacramento 5389489, California 5332921 95817
Sacramento 5389489, California 5332921 95817
Harbor-UCLA Medical Center
Torrance 5403022, California 5332921 90502
Torrance 5403022, California 5332921 90502
MedStar Washington Hospital Center - Washington Cancer Institute (WCI)
Washington D.C. 4140963, District of Columbia 4138106 20010
Washington D.C. 4140963, District of Columbia 4138106 20010
University of Florida
Gainesville 4156404, Florida 4155751 32608
Gainesville 4156404, Florida 4155751 32608
Jackson Memorial Hospital, University of Miami
Miami 4164138, Florida 4155751 33136
Miami 4164138, Florida 4155751 33136
University of Miami - Miller School of Medicine
Miami 4164138, Florida 4155751 33136
Miami 4164138, Florida 4155751 33136
University of Louisville School of Medicine
Louisville 4299276, Kentucky 6254925 40202
Louisville 4299276, Kentucky 6254925 40202
Rutgers, The State University of New Jersey
New Brunswick 5101717, New Jersey 5101760 07103
New Brunswick 5101717, New Jersey 5101760 07103
Westchester Medical College
Valhalla 5142090, New York 5128638 10595
Valhalla 5142090, New York 5128638 10595
ECU Health Medical Center
Greenville 4469160, North Carolina 4482348 27834
Greenville 4469160, North Carolina 4482348 27834
Metro Health Medical Center
Cleveland 5150529, Ohio 5165418 44109
Cleveland 5150529, Ohio 5165418 44109
Ohio State University
Columbus 4509177, Ohio 5165418 43210
Columbus 4509177, Ohio 5165418 43210
Ascension St. John Medical Center
Tulsa 4553433, Oklahoma 4544379 74104
Tulsa 4553433, Oklahoma 4544379 74104
University of Pennsylvania - Perelman School of Medicine
Philadelphia 4560349, Pennsylvania 6254927 19104
Philadelphia 4560349, Pennsylvania 6254927 19104
UPMC
Pittsburgh 5206379, Pennsylvania 6254927 15213
Pittsburgh 5206379, Pennsylvania 6254927 15213
Allegheny Health Network
Pittsburgh 5206379, Pennsylvania 6254927 15224-1722
Pittsburgh 5206379, Pennsylvania 6254927 15224-1722
Baylor Scott & White Health
Dallas 4684888, Texas 4736286 75246
Dallas 4684888, Texas 4736286 75246
University of Texas Southwestern Medical Center
Dallas 4684888, Texas 4736286 75390-8857
Dallas 4684888, Texas 4736286 75390-8857
More Details
- NCT ID
- NCT05156983
- Status
- Recruiting
- Sponsor
- Takeda