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NCT05156983PHASE3Recruiting

A Study of TAK-330 to Reverse the Effects of Factor Xa Inhibitors For Adults Needing Urgent Surgery

Takeda

Start Date

8/24/2022

Completion Date

8/30/2028

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 Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

TAK-330

DRUG

SOC 4F-PCC

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Conditions

Coagulation Disorder

Locations

University of Arkansas Medical Sciences

Arkansas City, Arkansas 72205

United States

University of California Davis Health System

Sacramento, California 95817

United States

Denver Metro Orthopedics, P.C.

Englewood, Colorado 80012

United States

University of Florida

Gainesville, Florida 32608

United States

Rutgers, The State University of New Jersey

New Brunswick, New Jersey 07103

United States

ECU Health Medical Center

Greenville, North Carolina 27858

United States

Metro Health Medical Center

Cleveland, Ohio 44109

United States

Ohio State University

Columbus, Ohio 43210

United States

Ascension St. John Medical Center

Tulsa, Oklahoma 74104

United States

University of Pennsylvania - Perelman School of Medicine

Philadelphia, Pennsylvania 19104

United States

UPMC

Pittsburgh, Pennsylvania 15213

United States

University of Texas Southwestern Medical Center

Dallas, Texas 75390

United States

Carilion Medical Center

Virginia Beach, Virginia 24014

United States

Hospital Universitario Austral

Buenos Aires, B1629WWA

Argentina

Clinica Zabala

Ciudad Autonoma Buenos Aires, 1426

Argentina

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

Ciudad Autonoma Buenos Aires, CP1428

Argentina

Hospital Privado de Rosario

Santa Fe, 3000

Argentina

LKH - Universitaetsklinikum Graz

Graz, 8036

Austria

Landesklinikum Neunkirchen

Neunkirchen, 2620

Austria

ZOL

Genk, Limburg 3600

Belgium

Jessa Ziekenhuis Hospital

Hasselt, Limburg 3500

Belgium

AZ Groeninge

Kortrijk, 8500

Belgium

CHU UCL Namur

Therasse 1, 5530

Belgium

Irmandade da Santa Casa da Misericordia de Santos

Santos, São Paulo 11010-000

Brazil

Hospital de Clinicas de Ijui

Ijuí, 98700-000

Brazil

Hospital Sao Paulo

São Paulo, 5102

Brazil

Hamilton General Hospital

Hamilton, Ontario L8L 2X2

Canada

London Health Sciences Centre (LHSC) - University Hospital

London, Ontario N6A 5A5

Canada

Unity Health Toronto St Michaels Hospital

Toronto, Ontario M5N 1W8

Canada

Montreal General Hospital

Montreal, Quebec H3G 1A4

Canada

The Ottawa Hospital - General Campus

Ontario, K1H 8L6

Canada

CHU de Quebec- Hopital de l Enfant Jesus

Québec, G1J-1Z4

Canada

Fakultni nemocnice Brno

Jihlavska, 625 00

Czechia

Fakultni nemocnice v Motole

Prague (Praha), 15000

Czechia

Dept of II. interni klinika - gastroenterologie

Srobarova C, 100 34

Czechia

CHU Strasbourg - Hopital Hautepierre

Strasbourg, Bas Rhin 67098

France

Hospital michallon - CHUGA

Grenoble, 38043

France

Hopital Marie Lannelongue

Le Plessis-Robinson, 92350

France

Hôpital Lariboisière

Paris, 75010

France

GH Paris Saint Joseph

Paris, 75014

France

BG Klinikum Murnau gGmbH

Murnau am Staffelsee, Bavaria 82418

Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony 01307

Germany

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony 04103

Germany

Klinikum Dortmund gGmbH

Murnau am Staffelsee, 44137

Germany

Konstantopoulio General Hospital, N.Ionia

Nea Ionia, Attica 14233

Greece

Bekes Varmegyei Kozponti Korhaz

Békéscsaba, Attica 5700

Hungary

Ozdi Almasi Balogh Pal Korhaz

Szeged, Attica 6725

Hungary

Semmelweis Egyetem

Budapest, 1082

Hungary

Debreceni Egyetem

Debrecen, 4032

Hungary

Shamir Medical Center (Assaf Harofe)

Beer Yaacov, 70300

Israel

Soroka Medical Center

Beersheba, 8410101

Israel

Rambam Health Care Campus

Haifa, 3109601

Israel

Shaare Zedek Medical Center

Jerusalem, 9103102

Israel

Hadassah University Hospital - Ein Kerem

Jerusalem, 911200

Israel

Rabin MC

Petah Tikva, 49100

Israel

Chaim Sheba Medical Center

Ramat Gan, 5265601

Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906

Israel

Uniwersytecki Szpital Kliniczny nr 1 im. prof. Tadeusza Sokołowskiego PUM w Szczecinie

Szczecin, 71-252

Poland

Centro Hospitalar do Baixo Vouga, E.P.E. - Unidade de Aveiro

Aveiro, 3810-501

Portugal

Centro Hospitalar do Baixo Vouga, E.P.E. - Unidade de Aveiro

Aveiro, 3814-501

Portugal

Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E

Rua Conceição Fernandes, 4434-502

Portugal

Hospital Clinico Universitario de Salamanca

Salamnca, Salamanca 37007

Spain

Hospital Clinico Universitario de Valencia

Valencia, 46010

Spain

Hospital Universitari i Politecnic La Fe

Valencia, 46026

Spain