A Study of TAK-330 to Reverse the Effects of Factor Xa Inhibitors For Adults Needing Urgent Surgery
- Registration Number
- NCT05156983
- Lead Sponsor
- Takeda
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 328
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SOC 4F-PCC 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. TAK-330 25 IU/kg TAK-330 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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.
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 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.
Trial Locations
- Locations (48)
Ohio State University
🇺🇸Columbus, Ohio, United States
University of California Davis Health System
🇺🇸Sacramento, California, United States
University of Louisville School of Medicine
🇺🇸Louisville, Kentucky, United States
Jackson Memorial Hospital, University of Miami
🇺🇸Miami, Florida, United States
University of Miami - Miller School of Medicine
🇺🇸Miami, Florida, United States
Metro Health Medical Center
🇺🇸Cleveland, Ohio, United States
Westchester Medical College
🇺🇸Valhalla, New York, United States
ECU Health Medical Center
🇺🇸Greenville, North Carolina, United States
Ascension St. John Medical Center
🇺🇸Tulsa, Oklahoma, United States
University of Pennsylvania - Perelman School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Allegheny Health Network
🇺🇸Pittsburgh, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Jessa Ziekenhuis Hospital
🇧🇪Hasselt, Limburg, Belgium
Universitair Ziekenhuis Brussel
🇧🇪Jette, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Montreal General Hospital
🇨🇦Montreal, Quebec, Canada
Hamilton General Hospital
🇨🇦Hamilton, Ontario, Canada
London Health Sciences Centre (LHSC) - University Hospital
🇨🇦London, Ontario, Canada
CHU Toulouse - Hopital Rangueil
🇫🇷Toulouse, Haute Garonne, France
CHU Strasbourg - Hopital Hautepierre
🇫🇷Strasbourg cedex, Bas Rhin, France
Hospital michallon - CHUGA
🇫🇷Grenoble, France
CHU Clermont Ferrand - Hopital Gabriel Montpied
🇫🇷Clermont-Ferrand, France
Hopital Marie Lannelongue
🇫🇷Le Plessis-Robinson, France
Hôpital Lariboisière
🇫🇷Paris, France
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Baden Wuerttemberg, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
🇩🇪Dresden, Sachsen, Germany
BG Klinikum Murnau gGmbH
🇩🇪Murnau, Bayern, Germany
Universitaetsklinikum Leipzig AoeR
🇩🇪Leipzig, Sachsen, Germany
Hospital Clinico Universitario de Salamanca
🇪🇸Salamnca, Salamanca, Spain
Hospital Universitario Dr Peset
🇪🇸Valencia, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Denver Metro Orthopedics, P.C.
🇺🇸Englewood, Colorado, United States
KH St.Josef Braunau am Inn
🇦🇹Braunau am Inn, Austria
LKH - Universitaetsklinikum Graz
🇦🇹Graz, Austria
CHU UCL Namur
🇧🇪Yvoir, Belgium
Baylor Scott & White Health
🇺🇸Dallas, Texas, United States
Maastricht University Medical Center , Department of Anesthesiology & Pain Management
🇳🇱Maastricht, Limburg, Netherlands
ZOL
🇧🇪Genk, Limburg, Belgium
Hopital Cardiologique CHU Lille
🇫🇷Lille Cedex, Nord, France
Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E
🇵🇹Vila Nova de Gaia, Portugal
Rutgers, The State University of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Landesklinikum Neunkirchen
🇦🇹Neunkirchen, Austria
Centro Hospitalar do Baixo Vouga, E.P.E. - Unidade de Aveiro
🇵🇹Aveiro, Portugal
MedStar Washington Hospital Center - Washington Cancer Institute (WCI)
🇺🇸Washington, District of Columbia, United States
University of Florida
🇺🇸Gainesville, Florida, United States