Resumen

El objetivo de este estudio es determinar los efectos de TAK-330 en comparación con el concentrado de complejo protrombínico de cuatro factores (CCP-4F) como parte del tratamiento estándar, excluyendo Prothromplex Total, para la reversión de la anticoagulación en participantes tratados con inhibidores del Factor Xa que requieren cirugía urgente/procedimiento invasivo. El participante será asignado aleatoriamente a recibir TAK-330 o CCP-4F como estándar de atención antes de la cirugía. Los pacientes que participan en este estudio deberán ser hospitalizados. También serán contactados (mediante telesalud/llamada telefónica) 30 días después de la cirugía.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

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.
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.

Intervenciones

drug

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.

drug

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.

Ubicaciones

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

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

TAK-330

SOC 4F-PCC

Ubicaciones

Hospital Universitario Austral

Clinica Zabala

Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia - FLENI

Hospital Privado de Rosario

Patrocinadores

Contactos

Takeda Contact