FactOr XIa inhibiTion for the pRevention of venOus Thromboembolism in Patients Undergoing Total Knee Arthroplasty (FOXTROT)

A Randomized, Active-comparator-controlled, Multicenter Study to Assess the Safety and Efficacy of Different Doses of BAY1213790 for the Prevention of Venous Thromboembolism in Patients Undergoing Elective Primary Total Knee Arthroplasty, Open-label to Treatment and Observer-blinded to BAY1213790 Doses

This study was to compare the study drug BAY1213790 to existing therapies, i.e. enoxaparin or apixaban, for the prevention of blood clotting and safety in patients undergoing total knee arthroplasty (TKA). The study was open-label, but observer-blinded for the different doses of BAY1213790. This means that it was known which treatment was given, but it was not known which dose of BAY1213790 was administered.

Study Overview

• Status: Completed
• Conditions: Knee Arthroplasty, Total
• Intervention / Treatment: Drug: Enoxaparin; Drug: Apixaban; Drug: BAY1213790

• Study Type: Interventional
• Enrollment (Actual): 813
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sveti Georgi
  • Sofia, Bulgaria, 1527
    • UMHAT Tsaritsa Joanna-ISUL EAD Sofia
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Multiprofile Hospital for Active Treatm
• Canada
  • Ontario
    • Windsor, Ontario, Canada, N8W 1E6
      • Medical Investigative & Clinical Evaluation Inc.
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny
  • Ceske Budejovice, Czechia, 370 87
    • Nemocnice Ceske Budejovice, a.s.
  • Jindrichuv Hradec, Czechia, 377 38
    • Okresni nemocnice Jindrichuv Hradec
  • Pardubice, Czechia, 530 03
    • Regional Hospital Pardubice
• Greece
  • Kifisia, Greece, 14561
    • KAT General Hospital of Athens
  • Nea Ionia, Greece, 14233
    • Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA
  • Patras, Greece, 265 04
    • University General Hospital of Patras
  • Thessaloniki, Greece, 56403
    • Papageorgiou General Hospital of Thessaloniki
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Corporation
  • Haifa, Israel, 3436212
    • Lady Davis Carmel Medical Center
  • Kfar-Saba, Israel, 4428164
    • Meir Medical Center
  • Petah Tikva, Israel, 4941492
    • Clalit Health Services through Rabin Medical Center - Beilinson Campus
  • Rehovot, Israel, 7610001
    • Kaplan Medical Center
• Latvia
  • Liepaja, Latvia, LV-3414
    • Liepaja Regional Hospital
  • Riga, Latvia, LV-1004
    • Riga 2nd City Hospital
  • Riga, Latvia, LV-1005
    • Hospital of Traumatology and Orthopaedics
  • Valmiera, Latvia, LV-4201
    • Valmiera Hospital
• Lithuania
  • Kaunas, Lithuania, LT-44320
    • Kaunas clinical hospital (Laisves ave.)
  • Kaunas, Lithuania, LT-50009
    • Lithuanian University of Health Science
  • Klaipeda, Lithuania, LT-92288
    • PI Klaipedos University Hospital
  • Vilnius, Lithuania, LT-08661
    • Vilnius University Hospital Santaros Klinikos
  • Vilnius, Lithuania, LT-04130
    • Republican Vilnius University hospital
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny W Bialymstoku
  • Kielce, Poland
    • Wojewodzki Szpital Zespolony
  • Krakow, Poland, 31-826
    • Szpital Specjalistyczny im. Rydygiera
  • Lodz, Poland, 92-213
    • Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
  • Lublin, Poland, 20-718
    • Wojewodzki Szpital Specjalistyczny im. S. Wyszynskiego SPZOZ
  • Wroclaw, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny UM we Wroclawiu
• Portugal
  • Aveiro, Portugal, 3810-501
    • CHBV - Hospital Infante D. Pedro
  • Leiria, Portugal, 2410-197
    • CHL - Hospital Santo Andre
  • Viana do Castelo, Portugal, 4901-858
    • ULSAM - Hospital Santa Luzia
  • Lisboa
    • Alcabideche, Lisboa, Portugal, 2755-009
      • Hospital de Cascais
  • Setúbal
    • Setubal, Setúbal, Portugal, 2900-182
      • CHS - Hospital Ortopedico Sant Iago do Outao
• Russian Federation
  • Kurgan, Russian Federation, 640014
    • Russian Scientific Center n.a. acad. G.A. Ilizarov
  • Nizhny Novgorod, Russian Federation, 603155
    • Privolzhskiy Federal Medical Research Center
  • St. Petersburg, Russian Federation, 194354
    • City Hospital #2
  • St. Petersburg, Russian Federation, 195427
    • Sci-Res. Institute of Traumatology and Orthopaedia
  • Yaroslavl, Russian Federation, 150003
    • Clinical Hospital for Emergency Care n.a. N.V.Solovyov
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0084
      • Pretoria Academic Hospital New
  • Western Cape
    • Cape Town, Western Cape, South Africa
      • UCT Clinical Research Centre
    • Worcester, Western Cape, South Africa, 6850
      • Clinical Projects Research SA
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic I Provincial de Barcelona
  • Barcelona, Spain, 08035
    • Ciutat Sanitaria i Universitaria de la Vall d'Hebron
  • Jaén, Spain, 23009
    • Complejo Hospitalario de Jaén
  • Madrid, Spain, 28040
    • Hospital Clinico Universitario San Carlos
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Ciutat Sanitaria i Universitaria de Bellvitge
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Fundacion Hospital Alcorcon
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Cherkasy Reg Clinical Hospital of Cherkasy Reg Council
  • Ivano-Frankivsk, Ukraine, 76008
    • Ivano-Frankivsk Regional Clinical Hospital
  • Kyiv, Ukraine, 4107
    • Kyiv Regional Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged ≥18 years and undergoing elective primary, unilateral Total Knee Arthroplasty (TKA)
• Women of non-childbearing potential

Exclusion Criteria:

• High risk for clinically significant bleeding
• Prior deep vein thrombosis
• Body weight above 135 kg
• Creatinine clearance below 60 ml/min
• Recent (<6 months) myocardial infarction or ischemic stroke
• Contraindication listed in the local label of the comparator treatments
• Requirement for full dose anticoagulation or dual antiplatelet therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Enoxaparin; Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received enoxaparin for at least 10 days until venography was performed.	Drug: Enoxaparin; 40 mg enoxaparin administered as subcutaneous injection once daily
Active Comparator: Apixaban; Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received apixaban for at least 10 days until venography was performed.	Drug: Apixaban; 2.5 mg apixaban administered as tablet orally twice daily
Experimental: BAY1213790 0.3 mg/kg (post-surgery); Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 0.3 mg BAY1213790 once post-surgery.	Drug: BAY1213790; Single dose of BAY1213790 administered as intravenous infusion; Other Names: Osocimab
Experimental: BAY1213790 0.6 mg/kg (post-surgery); Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 0.6 mg BAY1213790 once post-surgery.	Drug: BAY1213790; Single dose of BAY1213790 administered as intravenous infusion; Other Names: Osocimab
Experimental: BAY1213790 1.2 mg/kg (post-surgery); Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 1.2 mg BAY1213790 once post-surgery.	Drug: BAY1213790; Single dose of BAY1213790 administered as intravenous infusion; Other Names: Osocimab
Experimental: BAY1213790 1.8 mg/kg (post-surgery); Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 1.8 mg BAY1213790 once post-surgery.	Drug: BAY1213790; Single dose of BAY1213790 administered as intravenous infusion; Other Names: Osocimab
Experimental: BAY1213790 0.3 mg/kg (pre-surgery); Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 0.3 mg BAY1213790 once pre-surgery.	Drug: BAY1213790; Single dose of BAY1213790 administered as intravenous infusion; Other Names: Osocimab
Experimental: BAY1213790 1.8 mg/kg (pre-surgery); Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 1.8 mg BAY1213790 once pre-surgery.	Drug: BAY1213790; Single dose of BAY1213790 administered as intravenous infusion; Other Names: Osocimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of composite endpoint consisting of asymptomatic DVT as detected by mandatory bilateral venography, objectively confirmed symptomatic DVT, non-fatal PE, fatal PE, unexplained death for which PE cannot be excluded	DVT - Deep vein thrombosis / PE - Pulmonary embolism All suspected events were reviewed and classified by the Central Independent Adjudication Committee.	Up to 15 days
Incidence of composite endpoint of major and clinically relevant non-major bleeding	All suspected events were reviewed and classified by the Central Independent Adjudication Committee.	Up to 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of composite endpoint of symptomatic DVT, non-fatal PE, fatal PE, unexplained death for which PE cannot be excluded up to Day 157 or objectively confirmed asymptomatic DVT up to Day 15	All suspected events were reviewed and classified by the Central Independent Adjudication Committee.	Up to 157 days
Incidence of composite endpoint of major and clinically relevant non-major bleeding	All suspected events were reviewed and classified by the Central Independent Adjudication Committee.	Up to 157 days

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Weitz JI, Bauersachs R, Becker B, Berkowitz SD, Freitas MCS, Lassen MR, Metzig C, Raskob GE. Effect of Osocimab in Preventing Venous Thromboembolism Among Patients Undergoing Knee Arthroplasty: The FOXTROT Randomized Clinical Trial. JAMA. 2020 Jan 14;323(2):130-139. doi: 10.1001/jama.2019.20687.

Helpful Links

• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2017
• Primary Completion (Actual): August 20, 2018
• Study Completion (Actual): January 2, 2019

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: September 7, 2017
• First Posted (Actual): September 8, 2017

Study Record Updates

• Last Update Posted (Actual): March 3, 2020
• Last Update Submitted That Met QC Criteria: February 28, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Anticoagulation; Venous thromboembolism; Deep vein thrombosis (DVT); Orthopedic surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban; Enoxaparin
• Other Study ID Numbers: 17664; 2016-002681-31 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No