TAK-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.
SOC 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.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
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.
Primary outcome measure(s)
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.
Trial sites (64)
Facility
City
Region
Status
University of Arkansas Medical Sciences
Arkansas City
Arkansas
Recruiting
University of California Davis Health System
Sacramento
California
Recruiting
Denver Metro Orthopedics, P.C.
Englewood
Colorado
Recruiting
University of Florida
Gainesville
Florida
Recruiting
Rutgers, The State University of New Jersey
New Brunswick
New Jersey
Recruiting
ECU Health Medical Center
Greenville
North Carolina
Recruiting
Metro Health Medical Center
Cleveland
Ohio
Recruiting
Ohio State University
Columbus
Ohio
Recruiting
Ascension St. John Medical Center
Tulsa
Oklahoma
Recruiting
University of Pennsylvania - Perelman School of Medicine
Philadelphia
Pennsylvania
Recruiting
UPMC
Pittsburgh
Pennsylvania
Recruiting
University of Texas Southwestern Medical Center
Dallas
Texas
Recruiting
Carilion Medical Center
Virginia Beach
Virginia
Recruiting
Hospital Universitario Austral
Buenos Aires
Argentina
Recruiting
Clinica Zabala
Ciudad Autonoma Buenos Aires
Argentina
Recruiting
Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia - FLENI
Ciudad Autonoma Buenos Aires
Argentina
Recruiting
Hospital Privado de Rosario
Santa Fe
Argentina
Recruiting
LKH - Universitaetsklinikum Graz
Graz
Austria
Recruiting
Landesklinikum Neunkirchen
Neunkirchen
Austria
Recruiting
ZOL
Genk
Limburg
Recruiting
Jessa Ziekenhuis Hospital
Hasselt
Limburg
Recruiting
AZ Groeninge
Kortrijk
Belgium
Recruiting
CHU UCL Namur
Therasse 1
Belgium
Recruiting
Irmandade da Santa Casa da Misericordia de Santos
Santos
São Paulo
Recruiting
Hospital de Clinicas de Ijui
Ijuí
Brazil
Recruiting
Hospital Sao Paulo
São Paulo
Brazil
Recruiting
Hamilton General Hospital
Hamilton
Ontario
Recruiting
London Health Sciences Centre (LHSC) - University Hospital
London
Ontario
Recruiting
Unity Health Toronto St Michaels Hospital
Toronto
Ontario
Recruiting
Montreal General Hospital
Montreal
Quebec
Recruiting
The Ottawa Hospital - General Campus
Ontario
Canada
Recruiting
CHU de Quebec- Hopital de l Enfant Jesus
Québec
Canada
Recruiting
Fakultni nemocnice Brno
Jihlavska
Czechia
Recruiting
Fakultni nemocnice v Motole
Prague (Praha)
Czechia
Recruiting
Dept of II. interni klinika - gastroenterologie
Srobarova C
Czechia
Recruiting
CHU Strasbourg - Hopital Hautepierre
Strasbourg
Bas Rhin
Recruiting
Hospital michallon - CHUGA
Grenoble
France
Completed
Hopital Marie Lannelongue
Le Plessis-Robinson
France
Completed
Hôpital Lariboisière
Paris
France
Completed
GH Paris Saint Joseph
Paris
France
Recruiting
+ 24 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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