A Study of JNJ-70033093 (BMS-986177) Versus Subcutaneous Enoxaparin in Participants Undergoing Elective Total Knee Replacement Surgery
AXIOMATIC-TKR
A Randomized, Open-Label, Study Drug-Dose Blind, Multicenter Study to Evaluate the Efficacy and Safety of JNJ-70033093 (BMS-986177), an Oral Factor XIa Inhibitor, Versus Subcutaneous Enoxaparin in Subjects Undergoing Elective Total Knee Replacement Surgery
3 other identifiers
interventional
1,242
18 countries
117
Brief Summary
The purpose of this study is to determine the efficacy of JNJ-70033093 in preventing total venous thromboembolism (VTE) events (proximal and/or distal deep vein thrombosis \[DVT\] \[asymptomatic confirmed by venography assessment or objectively confirmed symptomatic\], nonfatal pulmonary embolism \[PE\], or any death) during the treatment period.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2019
117 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 25, 2019
CompletedFirst Posted
Study publicly available on registry
March 27, 2019
CompletedStudy Start
First participant enrolled
June 17, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 6, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 6, 2021
CompletedResults Posted
Study results publicly available
July 15, 2022
CompletedMarch 30, 2025
March 1, 2025
1.8 years
March 25, 2019
April 6, 2022
March 28, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
Total VTE was defined as the composite of clinical events committee (CEC)-adjudicated proximal and/or distal Deep Vein Thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal pulmonary embolism (PE), or any death.
Up to Day 14
Secondary Outcomes (29)
Number of Participants With Any Bleeding Event (CEC-adjudicated)
Up to Day 14; Up to Day 52
Number of Participants With Total VTE (CEC-adjudicated)
Up to Day 52
Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated)
Up to Day 14, Up to Day 52
Number of Participants With Major Bleeding Events (CEC-adjudicated)
Up to Day 14; Up to Day 52
Number of Participants With CRNM Bleeding Events (CEC-adjudicated)
Up to Day 14; Up to Day 52
- +24 more secondary outcomes
Study Arms (8)
Group A: JNJ-70033093 25 mg + Placebo BID
EXPERIMENTALParticipants will receive JNJ-70033093 25 milligram (mg) (1\*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days.
Group B: JNJ-70033093 50 mg BID
EXPERIMENTALParticipants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.
Group C: JNJ-70033093 100 mg + Placebo BID
EXPERIMENTALParticipants will receive JNJ-70033093 100 mg (1\*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.
Group D: JNJ-70033093 200 mg BID
EXPERIMENTALParticipants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID orally for 10 to 14 postoperative days.
Group E: JNJ-70033093 25 mg Once Daily + Placebo
EXPERIMENTALParticipants will receive JNJ-70033093 25 mg (1\*25 mg capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.
Group F: JNJ-70033093 200 mg Once Daily + Placebo
EXPERIMENTALParticipants will receive JNJ-70033093 200 mg (2\*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.
Group G: JNJ-70033093 50 mg once daily + Placebo
EXPERIMENTALParticipants will receive JNJ-70033093 50 mg (2\*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.
Group I: Enoxaparin 40 mg Once Daily
ACTIVE COMPARATORParticipants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
Interventions
Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days.
Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.
Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) BID, orally for 10 to 14 postoperative days.
Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days.
Participants will receive placebo matching to JNJ-70033093, orally.
Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
Eligibility Criteria
You may qualify if:
- Medically stable and appropriate for anticoagulant prophylaxis as determined by the investigator on the basis of physical examination, medical history, and vital signs performed as part of screening for elective total knee replacement (TKR) surgery
- Medically stable and appropriate for anticoagulant prophylaxis on the basis of clinical laboratory tests performed as part of local standard-of-care as part of screening for elective TKR surgery
- Has plans to undergo an elective primary unilateral TKR surgery
- A woman must be- a) Not of childbearing potential; b) Of childbearing potential and practicing a highly effective method of contraception (failure rate of less than \[\<\]1 percent \[%\] per year when used consistently and correctly) and agrees to remain on a highly effective method for the duration of study drug with JNJ-70033093 plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 34 days after the completion of treatment, pregnancy testing (serum or urine) prior to the first dose of study drug
- Willing and able to adhere to the lifestyle restrictions specified in this protocol
You may not qualify if:
- History of any condition for which the use of low molecular-weight heparin (LMWH) is not recommended in the opinion of the investigator (for example, previous allergic reaction, creatinine clearance \<30 milliliter per minute \[mL/minute\])
- History of severe hepatic impairment
- Planned bilateral revision or unicompartmental procedure
- Unable to undergo venography (for example, due to contrast agent allergy, poor venous access, or impaired renal function that would increase the risk of contrast-induced nephropathy
- Known previous pulmonary embolism (PE) or deep vein thrombosis (DVT) in either lower extremity
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Janssen Research & Development, LLClead
- Bristol-Myers Squibbcollaborator
Study Sites (117)
Central Research Associates, Inc.
Birmingham, Alabama, 35205, United States
Arizona Research Center
Phoenix, Arizona, 85053, United States
Bowen Hefley Orthopedics
Little Rock, Arkansas, 72205, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502, United States
Denver Metro Orthopedics, PC
Englewood, Colorado, 80113, United States
DMI Research
Pinellas Park, Florida, 33782, United States
Gulfcoast Research Institute
Sarasota, Florida, 34232, United States
University Orthopedic and Joint Replacement Center
Tamarac, Florida, 33321, United States
Memorial Hermann Memorial City Medical Center
Houston, Texas, 77024, United States
Hospital Britanico de Buenos Aires
Buenos Aires, C1280AEB, Argentina
Clinica Adventista Belgrano
CABA, C1430EGF, Argentina
Hospital San Roque
Córdoba, 5000, Argentina
Clínica Chutro
Córdoba, X5000EPU, Argentina
Hospital Italiano La Plata
La Plata, B1900AXI, Argentina
Instituto de Investigaciones Clinicas Rosario
Rosario, S2000BIF, Argentina
Sanatorio Corporación Médica de General San Martín
San Martín, B1650BNB, Argentina
ZNA Middelheim
Antwerp, 2020, Belgium
Ziekenhuis Oost-Limburg
Genk, 3600, Belgium
Jessa Ziekenhuis
Hasselt, 3500, Belgium
ZNA Jan Palfijn
Merksem, 2170, Belgium
Hospital Sao Francisco de Assis
Belo Horizonte, 30360-290, Brazil
Hospital e Maternidade Dr Christovao da Gama S.A
Santo André, 09030-010, Brazil
Hospital Estadual Mario covas
Santo André, 09190-615, Brazil
University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski
Pleven, 5800, Bulgaria
Acibadem City Clinic Tokuda Hospital
Sofa, 1407, Bulgaria
University Multiprofile Hospital Sofiamed Sofia
Sofia, 1330, Bulgaria
MHAT Tzaritza Joanna
Sofia, 1527, Bulgaria
Medical Center - Medical Complex BEROE EOOD
Stara Zagora, 6000, Bulgaria
Lakeridge Health
Ajax, Ontario, L1S 2J4, Canada
Hamilton Health Sciences Corporation
Hamilton, Ontario, L8V1C3, Canada
The Ottawa Hospital Research Institute
Ottawa, Ontario, K1H 8L6, Canada
Medical Investigative and Clinical Evaluation Inc
Windsor, Ontario, N8W 1E6, Canada
General Hospital of Attiki 'KAT'
Kifissia, 14561, Greece
General Hospital of Nea Ionia 'Konstantopoulio'
Nea Ionia, 14233, Greece
University General Hospital of Rio Patras
Pátrai, 26504, Greece
Papageorgiou General Hospital
Thessaloniki, 56403, Greece
Semmelweis Egyetem
Budapest, 1085, Hungary
Debreceni Egyetem
Debrecen, 4032, Hungary
Petz Aladar Megyei Oktato Korhaz
Gyõr, 9023, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
Kaposvár, 7400, Hungary
Bacs-kiskun Megyei Korhaz
Kecskemét, 6000, Hungary
Szegedi Tudomanyegyetem
Szeged, 6725, Hungary
Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz
Székesfehérvár, 8000, Hungary
MAV Korhaz es Rendelointezet
Szolnok, 5000, Hungary
Rambam Medical Center
Haifa, 31096, Israel
Carmel Medical Center
Haifa, 34362, Israel
Meir Medical Center
Kfar Saba, 44281, Israel
Kaplan Medical Center
Rehovot, 7610001, Israel
Cliniche Humanitas Gavazzeni
Bergamo, 24125, Italy
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, 24127, Italy
Istituto Ortopedico Rizzoli
Bologna, 40136, Italy
Policlinico S. Matteo
Pavia, 27100, Italy
Istituto Clinico Humanitas
Rozzano, 20089, Italy
A.O.U. Città della Salute e della Scienza
Torino, 10126, Italy
Matsudo City General Hospital
Chiba, 270-2296, Japan
Hakodate Goryoukaku Hospital
Hakodate, 040 8611, Japan
Japanese Red Cross Hamamatsu Hospital
Hamamatsu, 434-8533, Japan
Itami City Hospital
Itami-shi, 664-8540, Japan
Yonemori Hospital
Kagoshima, 890-0062, Japan
Japan Community Health care Organization Kyushu Hospital
Kitakyushu-shi, 806-8501, Japan
Marunouchi Hospital
Matsumoto, 390-8601, Japan
Chubu Rosai Hospital
Nagoya, 455-8530, Japan
Juntendo University Nerima Hospital
Nerima-Ku, 177-8521, Japan
National Hospital Organization Okayama Medical Center
Okayama, 701-1192, Japan
Yuuai Medical Center
Okinawa, 901-0224, Japan
Japan Community Health Care Organization Saitama Medical Center
Saitama, 350-8550, Japan
Saitama City Hospital
Saitama-shi, 336-8522, Japan
Nagano Prefectural Shinshu Medical Center
Suzaka, 386-8610, Japan
Juntendo University Hospital
Tokyo, 113-8431, Japan
Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Bielsku Podlaskim Oddzial Urazowo Ortopedyczny
Bielsk Podlaski, 17 100, Poland
Szpital Ogolny im. W. Ginela, Oddzial Urazowo-Ortopedyczny
Grajewo, 19-200, Poland
Wojewodzki Szpital Zespolony w Kielcach, Klinika Chirurgii Ortopedyczno-Urazowej
Kielce, 25-001, Poland
Oddzial Ortopedii i Traumatologii Narzadu Ruchu Szpital Specjalistyczny im Ludwika Rydygiera
Krakow, 31 826, Poland
CSK UM Klinika Ortopedii
Lodz, 92-213, Poland
Oddzial Urazowo-Ortopedyczny Wojewodzki Szpital Specjalistyczny
Lublin, 20-718, Poland
Oddzial Ortopedii Specjalistyczny Szpital im. E.Szczeklika
Tarnów, 33-100, Poland
Oddzial Chirurgii Urazowej iOrtopedycznej Wojewodzki Szpital Brodnowski SPZOZ
Warsaw, 03 242, Poland
Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
Wroclaw, 50 556, Poland
Centro Hospitalar do Baixo Vouga - Hospital Infante Dom Pedro
Aveiro, 3810-501, Portugal
Hosp de Cascais
Cascais, 2755-009, Portugal
H. Santo António - Centro Hospitalar do Porto
Porto, 4099-001, Portugal
CHS - Hosp. Orto. Sant'Iago do Outao
Setúbal, 2900-180, Portugal
ULSAM, EPE - Hospital de Santa Luzia
Viana do Castelo, 4904-858, Portugal
National Medical Research Center of Traumatology and Orthopaedics n.a. G.A. Ilizarov
Kurgan, 640014, Russia
Private Healthcare Institution 'Clinical Hospital 'RZD-Medcine' n.a. N.A.Semashko'
Moscow, 109386, Russia
Privolzhsky Regional Medical Center of Federal Medical and Biological Agency
Nizhny Novgorod, 603137, Russia
National medical research center of Traumatology and Orthopaedics n.a. R.R.Vreden
Saint Petersburg, 195427, Russia
State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin
Samara, 443095, Russia
Smolensk Federal Center of Traumatology, Orthopedics and Endoprothesis Replacement
Smolensk, 214031, Russia
Sochi City Hospital #4
Sochi, 354057, Russia
Steve Biko Academic Hospital
Pretoria, 0001, South Africa
Clinical Project Research SA
Worcester, 6850, South Africa
Hosp. Univ. Fundacion Alcorcon
Alcorcón, 28922, Spain
Hosp. Univ. Germans Trias I Pujol
Badalona, 08916, Spain
Hosp Clinic de Barcelona
Barcelona, 08036, Spain
Hosp. Univ. de Bellvitge
Barcelona, 08907, Spain
Hosp Univ Vall D Hebron
Barcelona, 8035, Spain
Complejo Hospitalario de Jaen
Jaén, 23007, Spain
Hosp. Univ. 12 de Octubre
Madrid, 28041, Spain
Hosp. Univ. La Paz
Madrid, 28046, Spain
Corporacio Sanitari Parc Tauli
Sabadell, 08208, Spain
Hosp. Clinico Univ. de Valencia
Valencia, 46010, Spain
Hosp. Univ. I Politecni La Fe
Valencia, 46026, Spain
Adana City Hospital
Adana, 01060, Turkey (Türkiye)
Diskapi Yildırim Beyazid Training and Research Hospital
Ankara, 06110, Turkey (Türkiye)
Yıldırım Beyazıt University Yenimahalle Training and Research Hospital
Ankara, 06370, Turkey (Türkiye)
Antalya Training And Research Hospital
Antalya, 07100, Turkey (Türkiye)
Bakirkoy Training and Research Hospital
Istanbul, 34147, Turkey (Türkiye)
Sisli Etfal Research Training Hospital
Istanbul, 34371, Turkey (Türkiye)
Izmir Tepecik Training and Research Hospital
Izmir, 35180, Turkey (Türkiye)
Ivano-Frankivsk Regional Clinical Hospital
Ivano-Frankivsk, 76008, Ukraine
Institute of Spine and JointPathology named after Prof.Sytenko of NationalAcademy of MedicalSciences
Kharkiv, 61024, Ukraine
Municipal Institution of Health Care 'Kharkiv Regional Clinical Traumatology Hospital'
Kharkiv, 61176, Ukraine
Kyiv Regional Clinical Hospital
Kyiv, 04107, Ukraine
Communal Institution of Lviv Regional Council 'Lypa Lviv Regional Hospital'
Lviv-Vynnyky, 79495, Ukraine
Municipal Non-profit Enterprise 'Odesa Regional Clinical Hospital' Odesa Regional Council
Odesa, 65025, Ukraine
Vinnytsya Regional Clinical Hospital named after M.I.Pirogov
Vinnytsia, 21018, Ukraine
Related Publications (2)
Whiteson HZ, Frishman WH. Factor XI/XIa Inhibitors: A New Approach to Anticoagulation. Cardiol Rev. 2025 Jul-Aug 01;33(4):306-311. doi: 10.1097/CRD.0000000000000624. Epub 2023 Dec 1.
PMID: 38038437DERIVEDWeitz JI, Strony J, Ageno W, Gailani D, Hylek EM, Lassen MR, Mahaffey KW, Notani RS, Roberts R, Segers A, Raskob GE; AXIOMATIC-TKR Investigators. Milvexian for the Prevention of Venous Thromboembolism. N Engl J Med. 2021 Dec 2;385(23):2161-2172. doi: 10.1056/NEJMoa2113194. Epub 2021 Nov 15.
PMID: 34780683DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Director Clinical Development
- Organization
- Janssen Research & Development, LLC
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- Treatment arms and study drug dose regimens will be blinded.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 25, 2019
First Posted
March 27, 2019
Study Start
June 17, 2019
Primary Completion
April 6, 2021
Study Completion
April 6, 2021
Last Updated
March 30, 2025
Results First Posted
July 15, 2022
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will share
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinicaltrials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu