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

NCT05156983 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: TAK-330-30012021-004138-122022-503012-16-00
• Study Type: interventional
• Target: 328
• Locations: 15 countries
• Sites: 64

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.

Conditions

Coagulation Disorder

Keywords

Reversal of Factor Xa inhibitors

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Intraoperative Effective Hemostasis

  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.

  At the end of the surgery/procedure

Secondary Outcomes (7)

• Percentage of Participants With Postoperative Effective Hemostasis

  At 24 hours after the end of investigational product infusion

• Percentage of Participants With Intraoperative Effective Hemostasis Based on Hemostatic Efficacy Rating Algorithm

  At the end of the surgery/procedure

• 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 Units of Packed Red Blood Cells (PRBCs) Administered to Achieve Bleeding Control

  Within 24 hours after the end of investigational product infusion

• 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)

Study Arms (2)

TAK-330 25 IU/kg

EXPERIMENTAL

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.

Drug: TAK-330

SOC 4F-PCC

ACTIVE COMPARATOR

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.

Drug: SOC 4F-PCC

Interventions

TAK-330 DRUG

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.

TAK-330 25 IU/kg

SOC 4F-PCC DRUG

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.

SOC 4F-PCC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Takeda: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (64)

University of Arkansas Medical Sciences

Arkansas City, Arkansas, 72205, United States

RECRUITING

University of California Davis Health System

Sacramento, California, 95817, United States

RECRUITING

Denver Metro Orthopedics, P.C.

Englewood, Colorado, 80012, United States

RECRUITING

University of Florida

Gainesville, Florida, 32608, United States

RECRUITING

Rutgers, The State University of New Jersey

New Brunswick, New Jersey, 07103, United States

RECRUITING

ECU Health Medical Center

Greenville, North Carolina, 27858, United States

RECRUITING

Metro Health Medical Center

Cleveland, Ohio, 44109, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Ascension St. John Medical Center

Tulsa, Oklahoma, 74104, United States

RECRUITING

University of Pennsylvania - Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

UPMC

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Carilion Medical Center

Virginia Beach, Virginia, 24014, United States

RECRUITING

Hospital Universitario Austral

Buenos Aires, B1629WWA, Argentina

RECRUITING

Clinica Zabala

Ciudad Autonoma Buenos Aires, 1426, Argentina

RECRUITING

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

Ciudad Autonoma Buenos Aires, CP1428, Argentina

RECRUITING

Hospital Privado de Rosario

Santa Fe, 3000, Argentina

RECRUITING

LKH - Universitaetsklinikum Graz

Graz, 8036, Austria

RECRUITING

Landesklinikum Neunkirchen

Neunkirchen, 2620, Austria

RECRUITING

ZOL

Genk, Limburg, 3600, Belgium

RECRUITING

Jessa Ziekenhuis Hospital

Hasselt, Limburg, 3500, Belgium

RECRUITING

AZ Groeninge

Kortrijk, 8500, Belgium

RECRUITING

CHU UCL Namur

Therasse 1, 5530, Belgium

RECRUITING

Irmandade da Santa Casa da Misericordia de Santos

Santos, São Paulo, 11010-000, Brazil

RECRUITING

Hospital de Clinicas de Ijui

Ijuí, 98700-000, Brazil

RECRUITING

Hospital Sao Paulo

São Paulo, 5102, Brazil

RECRUITING

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

RECRUITING

London Health Sciences Centre (LHSC) - University Hospital

London, Ontario, N6A 5A5, Canada

RECRUITING

Unity Health Toronto St Michaels Hospital

Toronto, Ontario, M5N 1W8, Canada

RECRUITING

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

RECRUITING

The Ottawa Hospital - General Campus

Ontario, K1H 8L6, Canada

RECRUITING

CHU de Quebec- Hopital de l Enfant Jesus

Québec, G1J-1Z4, Canada

RECRUITING

Fakultni nemocnice Brno

Jihlavska, 625 00, Czechia

RECRUITING

Fakultni nemocnice v Motole

Prague (Praha), 15000, Czechia

RECRUITING

Dept of II. interni klinika - gastroenterologie

Srobarova C, 100 34, Czechia

RECRUITING

CHU Strasbourg - Hopital Hautepierre

Strasbourg, Bas Rhin, 67098, France

RECRUITING

Hospital michallon - CHUGA

Grenoble, 38043, France

COMPLETED

Hopital Marie Lannelongue

Le Plessis-Robinson, 92350, France

COMPLETED

Hôpital Lariboisière

Paris, 75010, France

COMPLETED

GH Paris Saint Joseph

Paris, 75014, France

RECRUITING

BG Klinikum Murnau gGmbH

Murnau am Staffelsee, Bavaria, 82418, Germany

RECRUITING

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, 01307, Germany

RECRUITING

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony, 04103, Germany

RECRUITING

Klinikum Dortmund gGmbH

Murnau am Staffelsee, 44137, Germany

RECRUITING

Konstantopoulio General Hospital, N.Ionia

Nea Ionia, Attica, 14233, Greece

RECRUITING

Bekes Varmegyei Kozponti Korhaz

Békéscsaba, Attica, 5700, Hungary

RECRUITING

Ozdi Almasi Balogh Pal Korhaz

Szeged, Attica, 6725, Hungary

RECRUITING

Semmelweis Egyetem

Budapest, 1082, Hungary

RECRUITING

Debreceni Egyetem

Debrecen, 4032, Hungary

RECRUITING

Shamir Medical Center (Assaf Harofe)

Beer Yaacov, 70300, Israel

RECRUITING

Soroka Medical Center

Beersheba, 8410101, Israel

RECRUITING

Rambam Health Care Campus

Haifa, 3109601, Israel

RECRUITING

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

RECRUITING

Hadassah University Hospital - Ein Kerem

Jerusalem, 911200, Israel

RECRUITING

Rabin MC

Petah Tikva, 49100, Israel

RECRUITING

Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

RECRUITING

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

Szczecin, 71-252, Poland

RECRUITING

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

Aveiro, 3810-501, Portugal

RECRUITING

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

Aveiro, 3814-501, Portugal

RECRUITING

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

Rua Conceição Fernandes, 4434-502, Portugal

RECRUITING

Hospital Clinico Universitario de Salamanca

Salamnca, Salamanca, 37007, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

RECRUITING

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Hemostatic Disorders

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Central Study Contacts

Takeda Contact

CONTACT

+1-877-825-3327; medinfoUS@takeda.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Adaptive parallel-group sequential design.

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: December 14, 2021
• Study Start: August 24, 2022
• Primary Completion (Estimated): April 12, 2028
• Study Completion (Estimated): April 12, 2028
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

BR (3); GR (1); PL (1); US (13); DE (4); AR (4); CZ (3); AU (2); FR (5); HU (4); IL (8); CA (6); BE (4); ES (3); PT (3)