Clinical trial NCT05156983: A Study of TAK-330 to Reverse the Effects of Factor Xa Inhibitors For Adults Needing Urgent Surgery
Official title: A Phase 3, Prospective, Randomized, Open-label, Adaptive Group Sequential, Multicenter Trial With Blinded Endpoint Assessment to Evaluate the Efficacy and Safety of TAK-330 for the Reversal of Direct Oral Factor Xa Inhibitor-induced Anticoagulation in Patients Requiring Urgent Surgery/Invasive Procedure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Coagulation Disorder
Keywords: Reversal of Factor Xa inhibitors
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2021-12-14
Enrollment: 328
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Adaptive parallel-group sequential design.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 outcomes:
measure: Percentage of Participants With Intraoperative Effective Hemostasis
timeFrame: At the end of the surgery/procedure
Secondary outcomes:
measure: Percentage of Participants With Postoperative Effective Hemostasis
timeFrame: At 24 hours after the end of investigational product infusion
measure: Percentage of Participants With Intraoperative Effective Hemostasis Based on Hemostatic Efficacy Rating Algorithm
timeFrame: At the end of the surgery/procedure
measure: Number of Participants With Usage of Blood Products or Non-Study Hemostatic Agents for Bleeding Control
timeFrame: Within 24 hours after the end of investigational product infusion
measure: Number of Units of Packed Red Blood Cells (PRBCs) Administered to Achieve Bleeding Control
timeFrame: Within 24 hours after the end of investigational product infusion
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interests (AESIs)
timeFrame: Within 30 days after the end of the surgery/invasive procedure (up to 33 days)
measure: Number of Participants With Thrombotic Events
timeFrame: Within 30 days after the end of the surgery/invasive procedure (up to 33 days)
measure: Number of Participants With Deaths Within 30 Days Post-Surgery/Invasive Procedure
timeFrame: Within 30 days post-surgery/invasive procedure (up to 33 days)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Englewood
country: United States
facility: Denver Metro Orthopedics, P.C.
state: Colorado
city: Washington
country: United States
facility: MedStar Washington Hospital Center - Washington Cancer Institute (WCI)
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital, University of Miami
state: Florida
city: Miami
country: United States
facility: University of Miami - Miller School of Medicine
state: Florida
city: Louisville
country: United States
facility: University of Louisville School of Medicine
state: Kentucky
city: New Brunswick
country: United States
facility: Rutgers, The State University of New Jersey
state: New Jersey
city: Valhalla
country: United States
facility: Westchester Medical College
state: New York
city: Greenville
country: United States
facility: ECU Health Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Metro Health Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Tulsa
country: United States
facility: Ascension St. John Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania - Perelman School of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Scott & White Health
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Braunau am Inn
country: Austria
facility: KH St.Josef Braunau am Inn
city: Graz
country: Austria
facility: LKH - Universitaetsklinikum Graz
city: Neunkirchen
country: Austria
facility: Landesklinikum Neunkirchen
city: Genk
country: Belgium
facility: ZOL
state: Limburg
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis Hospital
state: Limburg
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Leuven
country: Belgium
facility: UZ Leuven
city: Yvoir
country: Belgium
facility: CHU UCL Namur
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre (LHSC) - University Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Strasbourg cedex
country: France
facility: CHU Strasbourg - Hopital Hautepierre
state: Bas Rhin
city: Toulouse
country: France
facility: CHU Toulouse - Hopital Rangueil
state: Haute Garonne
city: Lille Cedex
country: France
facility: Hopital Cardiologique CHU Lille
state: Nord
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand - Hopital Gabriel Montpied
city: Grenoble
country: France
facility: Hospital michallon - CHUGA
city: Le Plessis-Robinson
country: France
facility: Hopital Marie Lannelongue
city: Paris
country: France
facility: Hôpital Lariboisière
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
state: Baden Wuerttemberg
city: Murnau
country: Germany
facility: BG Klinikum Murnau gGmbH
state: Bayern
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
state: Sachsen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AoeR
state: Sachsen
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center , Department of Anesthesiology & Pain Management
state: Limburg
city: Aveiro
country: Portugal
facility: Centro Hospitalar do Baixo Vouga, E.P.E. - Unidade de Aveiro
city: Aveiro
country: Portugal
facility: Centro Hospitalar do Baixo Vouga, E.P.E. - Unidade de Aveiro
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E
city: Salamnca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
state: Salamanca
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Dr Peset
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: