A Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Participants Undergoing Elective Total Knee Replacement Surgery
- Conditions
- VTE Prophylaxis With Anticoagulation After Total Knee Replacement Surgery
- Interventions
- Drug: JNJ-64179375 0.3 mg/kgDrug: JNJ-64179375 0.6 mg/kgDrug: JNJ-64179375 1.2 mg/kgDrug: JNJ-64179375 (Dose to be Determined)Drug: JNJ-64179375 A mg/kgDrug: JNJ-64179375 B mg/kgDrug: JNJ-64179375 C mg/kgDrug: JNJ-64179375 D mg/kgDrug: Placebo JNJ-64179375Drug: Apixaban placeboDrug: Apixaban 2.5 mg
- Registration Number
- NCT03251482
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The primary purpose of Part 1 in this study is to assess the safety and tolerability of JNJ-64179375 for each dose level for dose escalation and any bleeding events (the composite of major, clinically relevant non-major, and minimal bleeding events) for the selection of doses for Part 2. The primary purpose of Part 2 is to assess the efficacy dose response of JNJ-64179375 for the prevention of total venous thromboembolism (VTE) (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).
- Detailed Description
This study has 2 parts, dose escalation and dose-response evaluation, and will be conducted in participants undergoing primary unilateral elective Total Knee Replacement (TKR) surgery. Participants will participate in either Part 1 or Part 2 of study only. The study will be conducted in 3 phases: an up to 30-day screening phase before surgery, a 14-day double-blind dosing phase, and a 16-week follow-up phase. Safety evaluations will include monitoring of all nonserious and serious adverse events, clinical laboratory tests, vital signs measurements, and physical examinations. Pharmacokinetics (dense and sparse), pharmacodynamic (PD), health resource utilization, and immunogenicity samples will also be assessed. The total study duration of participant's participation in Part 1 or part 2 after randomization will be approximately 18 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 308
- Weight greater than or equal to (>=) 40 kg to less than or equal to (<=) 150 kilogram (kg)
- Medically appropriate for postoperative anticoagulant prophylaxis as determined by the investigator
- Has undergone an elective primary unilateral total knee replacement (TKR)
- Before randomization, a woman must not be of childbearing potential defined as postmenopausal (defined as no menses for 12 months without an alternative medical cause) and/ or permanently sterile (include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy)
- Contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
- Any condition for which the use of apixaban is not recommended in the opinion of the investigator
- Bilateral, revision or unicompartmental procedure
- Known or suspected hypersensitivity or intolerance to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies or antibody fragments, or any of the excipients of JNJ-64179375
- Unable to undergo venography
- Known previous deep vein thrombosis (DVT) in either lower extremity
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Cohort 2 (0.6 mg/kg JNJ-64179375/Apixaban) Apixaban placebo Participants will receive JNJ-64179375 0.6 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 2: Group A: JNJ-64179375 A mg/kg and apixaban placebo Apixaban placebo Participants will receive JNJ-64179375 Dose A mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days. Part 1: Cohort 1 (0.3 mg/kg JNJ-64179375/Apixaban) Apixaban 2.5 mg Participants will receive JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenously (IV) or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Cohort 2 (0.6 mg/kg JNJ-64179375/Apixaban) Apixaban 2.5 mg Participants will receive JNJ-64179375 0.6 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 2: Group B: JNJ-64179375 B mg/kg and apixaban placebo Apixaban placebo Participants will receive JNJ-64179375 Dose B mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days. Part 2: Group C: JNJ-64179375 C mg/kg and apixaban placebo Apixaban placebo Participants will receive JNJ-64179375 Dose C mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days. Part 1: Cohort 1 (0.3 mg/kg JNJ-64179375/Apixaban) JNJ-64179375 0.3 mg/kg Participants will receive JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenously (IV) or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Cohort 1 (0.3 mg/kg JNJ-64179375/Apixaban) Placebo JNJ-64179375 Participants will receive JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenously (IV) or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Cohort 1 (0.3 mg/kg JNJ-64179375/Apixaban) Apixaban placebo Participants will receive JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenously (IV) or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Cohort 2 (0.6 mg/kg JNJ-64179375/Apixaban) JNJ-64179375 0.6 mg/kg Participants will receive JNJ-64179375 0.6 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Cohort 2 (0.6 mg/kg JNJ-64179375/Apixaban) Placebo JNJ-64179375 Participants will receive JNJ-64179375 0.6 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Cohort 3 (1.2 mg/kg JNJ-64179375/Apixaban) JNJ-64179375 1.2 mg/kg Participants will receive JNJ-64179375 1.2 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Cohort 3 (1.2 mg/kg JNJ-64179375/Apixaban) Placebo JNJ-64179375 Participants will receive JNJ-64179375 1.2 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Cohort 3 (1.2 mg/kg JNJ-64179375/Apixaban) Apixaban placebo Participants will receive JNJ-64179375 1.2 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Cohort 3 (1.2 mg/kg JNJ-64179375/Apixaban) Apixaban 2.5 mg Participants will receive JNJ-64179375 1.2 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 4 (JNJ-64179375/Apixaban) JNJ-64179375 (Dose to be Determined) Participants will receive JNJ-64179375 Dose to be determined (TBD) based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 4 (JNJ-64179375/Apixaban) Placebo JNJ-64179375 Participants will receive JNJ-64179375 Dose to be determined (TBD) based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 4 (JNJ-64179375/Apixaban) Apixaban placebo Participants will receive JNJ-64179375 Dose to be determined (TBD) based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 4 (JNJ-64179375/Apixaban) Apixaban 2.5 mg Participants will receive JNJ-64179375 Dose to be determined (TBD) based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 5 (JNJ-64179375/Apixaban) JNJ-64179375 (Dose to be Determined) Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 5 (JNJ-64179375/Apixaban) Placebo JNJ-64179375 Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 5 (JNJ-64179375/Apixaban) Apixaban placebo Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 5 (JNJ-64179375/Apixaban) Apixaban 2.5 mg Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 6 (JNJ-64179375/Apixaban) JNJ-64179375 (Dose to be Determined) Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 6 (JNJ-64179375/Apixaban) Placebo JNJ-64179375 Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 6 (JNJ-64179375/Apixaban) Apixaban placebo Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 1: Optional Cohort 6 (JNJ-64179375/Apixaban) Apixaban 2.5 mg Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days. Part 2: Group D: JNJ-64179375 D mg/kg and apixaban placebo Apixaban placebo Participants will receive JNJ-64179375 Dose D mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days. Part 2: Group A: JNJ-64179375 A mg/kg and apixaban placebo JNJ-64179375 A mg/kg Participants will receive JNJ-64179375 Dose A mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days. Part 2: Group B: JNJ-64179375 B mg/kg and apixaban placebo JNJ-64179375 B mg/kg Participants will receive JNJ-64179375 Dose B mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days. Part 2: Group C: JNJ-64179375 C mg/kg and apixaban placebo JNJ-64179375 C mg/kg Participants will receive JNJ-64179375 Dose C mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days. Part 2: Group D: JNJ-64179375 D mg/kg and apixaban placebo JNJ-64179375 D mg/kg Participants will receive JNJ-64179375 Dose D mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days. Part 2: Group E: JNJ-64179375 placebo IV and apixaban 2.5 mg Placebo JNJ-64179375 Participants will receive JNJ-64179375 placebo (saline) IV as a single dose on Day 1 and apixaban 2.5 mg orally twice a day for 10 to 14 days. Part 2: Group E: JNJ-64179375 placebo IV and apixaban 2.5 mg Apixaban 2.5 mg Participants will receive JNJ-64179375 placebo (saline) IV as a single dose on Day 1 and apixaban 2.5 mg orally twice a day for 10 to 14 days.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with treatment-emergent bleeding events (BE) (adjudicated by CEC) were reported. Bleeding event was defined as the composite of major, clinically relevant nonmajor (CRNM), and minimal bleeding events assessed through the Day 10 to 14.
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with total VTE were reported. Total VTE was defined as the composite of 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 assessed through the Day 10 to 14 visit. 1 participant had an asymptomatic distal clot in the non-operated leg which is not counted in the Total VTE and 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
- Secondary Outcome Measures
Name Time Method Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with composite of major and CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.
Number of Participants With Major Bleeding Event (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with major bleeding events (BE) (adjudicated by CEC) were reported. Major Bleeding: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in hemoglobin (Hb) level of 20 grams per liter (g/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability.
Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding was defined as acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major bleeding event and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.
Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated) Up to Day 10 and 14 (visit observation period) Number of participants with major bleeding or CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.
Number of Participants With Minimal Bleeding Events (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with minimal bleeding events (adjudicated by CEC) were reported. Minimal bleeding event was defined as any bleeding event not met major or CRNM criteria.
Number of Participants With Major VTE (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with proximal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with nonfatal PE (adjudicated by CEC) were reported.
Number of Participants With Death (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with death (adjudicated by CEC) were reported.
Number of Participants With Proximal and Distal DVT (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with proximal and distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Number of Participants With Distal DVT (CEC-adjudicated) Up to Day 10 to 14 (visit observation period) Number of participants with distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Trial Locations
- Locations (103)
Municipal Institution Cherkasy Regional Hospital of Cherkasy Regional Council
🇺🇦Cherkasy, Ukraine
Denver Metro Orthopedics, PC
🇺🇸Englewood, Colorado, United States
ZNA Jan Palfijn
🇧🇪Merksem, Belgium
Sanatorio San Miguel
🇦🇷San Miguel, Argentina
Hospital Italiano de Buenos Aires
🇦🇷Caba, Argentina
Hospital San Roque
🇦🇷Córdoba, Argentina
ZNA Middelheim
🇧🇪Antwerpen, Belgium
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Universidade Federal de Minas Gerais (UFMG) - Faculdade de Medicina
🇧🇷Belo Horizonte, Brazil
Florida Research Associates, LLC
🇺🇸DeLand, Florida, United States
Avanza research
🇺🇸Pensacola, Florida, United States
Ziekenhuis Oost-Limburg
🇧🇪Genk, Belgium
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
Hospital e Maternidade Dr Christovão da Gama
🇧🇷Santo André, Brazil
Unicamp - Hospital de Clinicas
🇧🇷Campinas, Brazil
Uniort.e - Hospital de ortopedia
🇧🇷Londrina, Brazil
Acibadem City Clinic Tokuda Hospital
🇧🇬Sofa, Bulgaria
Source Trial Solutions Inc.
🇨🇦Kitchener, Ontario, Canada
Cliniche Humanitas Gavazzeni
🇮🇹Bergamo, Italy
The Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Matsudo City General Hospital
🇯🇵Chiba, Japan
Azienda Ospedaliera Papa Giovanni XXIII
🇮🇹Bergamo, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Yonemori Hospital
🇯🇵Kagoshima-shi, Japan
Hakodate Goryokaku Hospital
🇯🇵Hakodate, Japan
Riga 2nd Hospital
🇱🇻Riga, Latvia
Osaka Saiseikai Nakatsu Hospital
🇯🇵Osaka-shi, Japan
Hospital Miri
🇲🇾Miri, Malaysia
Oddzial Ortopedii Specjalistyczny Szpital im. E.Szczeklika
🇵🇱Tarnow, Poland
Privolzhsky Research Medical University of Ministry of Health of Russian Federation
🇷🇺Nizhny Novgorod, Russian Federation
State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin
🇷🇺Samara, Russian Federation
Hosp. Univ. Germans Trias I Pujol
🇪🇸Badalona, Spain
Bakirkoy Training and Research Hospital
🇹🇷Istanbul, Turkey
Istituto Ortopedico Rizzoli
🇮🇹Bologna, Italy
IRCCS Policlinico San Donato
🇮🇹S. Donato Milanese, Italy
Ospedale Mauriziano (Torino)
🇮🇹Torino, Italy
Umraniye Training and Research Hospital
🇹🇷Istanbul, Turkey
Hospital Estadual Mario covas
🇧🇷Santo André, Brazil
Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo
🇧🇷São Paulo, Brazil
Hosp. Clinico San Carlos
🇪🇸Madrid, Spain
Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Memorial Hermann Memorial City Medical Center
🇺🇸Houston, Texas, United States
University Orthopedic and Joint Replacement Center
🇺🇸Tamarac, Florida, United States
Clínica Adventista Belgrano
🇦🇷Caba, Argentina
Clínica Chutro
🇦🇷Córdoba, Argentina
Hospital Italiano La Plata
🇦🇷La Plata, Argentina
Sanatorio Britanico de Rosario
🇦🇷Rosario, Argentina
Irmandade da Santa Casa de Misericórdia de Marília
🇧🇷Marilia, Brazil
Hospital Sao Francisco de Assis
🇧🇷Belo Horizonte, Brazil
Military Medical Academy
🇧🇬Sofia, Bulgaria
Lakeridge Health Ajax
🇨🇦Ajax, Ontario, Canada
Multiprofile Hospital for Active Treatment Russe
🇧🇬Russe, Bulgaria
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
A.O.U. Città della Salute e della Scienza
🇮🇹Torino, Italy
Hospital Sultan Abdul Halim
🇲🇾Sungai Petani, Malaysia
Itami City Hospital
🇯🇵Itami-shi, Japan
Ritsuzankai Iida Hospital
🇯🇵Iida-shi, Japan
Bange Kousei General Hospital
🇯🇵Kawanuma-Gun, Japan
Tokushima Municipal Hospital
🇯🇵Tokushima-shi, Japan
Osaka Rosai Hospital
🇯🇵Osaka, Japan
Hospital of Traumatology and Orthopedics
🇱🇻Riga, Latvia
Yuaikai Tomishiro Central Hospital
🇯🇵Tomishiro, Japan
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
🇱🇹Kaunas, Lithuania
Klaipeda University Hospital
🇱🇹Klaipeda, Lithuania
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Malaysia
Oddzial Ortopedii i Traumatologii - Szpital Ogolny im. W.Ginela
🇵🇱Grajewo, Poland
Hospital Sibu
🇲🇾Sibu, Malaysia
Klinika Ortopedii i Traumatologii UMB
🇵🇱Bialystok, Poland
Klinika Ortopedii Gornoslaskie Centrum Medyczne
🇵🇱Katowice, Poland
Barnaul Federal Center of Traumatology, Orthopedics and Endoprothesis replacement
🇷🇺Barnaul, Russian Federation
Moscow City Clinical Hospital #1 n.a. N.I.Pirogov
🇷🇺Moscow, Russian Federation
Oddzial Chirurgii Urazowej iOrtopedycznej,Wojewodzki Szpital Brodnowski, SPZOZ
🇵🇱Warszawa, Poland
Russian Ilizarov Scientific Center For Restorative Traumatology And Ortopaedics
🇷🇺Kurgan, Russian Federation
St. Petersburg State Medical Institution City Multifunctional Hospital #2
🇷🇺Saint-Petersburg, Russian Federation
Clinical Emergency Hospital n.a. N.V. Solovyev
🇷🇺Yaroslavl, Russian Federation
Russian Research Institute of Traumatology and Orthopaedics n.a.R.R.Vreden
🇷🇺Saint-Petersburg, Russian Federation
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. Fund. Jimenez Diaz
🇪🇸Madrid, Spain
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
Corporacio Sanitari Parc Tauli
🇪🇸Sabadell, Spain
Hosp. Clinico Univ. de Santiago
🇪🇸Santiago de Compostela, Spain
Hosp. Univ. I Politecni La Fe
🇪🇸Valencia, Spain
Ankara Numune Research and Training Hospital
🇹🇷Ankara, Turkey
Dışkapı Yıldırım Beyazıd Training and Research Hospital
🇹🇷Ankara, Turkey
Yıldırım Beyazıt University Yenimahalle Training and Research Hospital
🇹🇷Ankara, Turkey
Yildirim Beyazit University Medical Faculty Ankara Atatürk Research and Training Hospital
🇹🇷Ankara, Turkey
Izmir Tepecik Training and Research Hospital
🇹🇷Izmir, Turkey
Municipal Institution of Health Care 'Kharkiv Regional Clinical Traumatology Hospital'
🇺🇦Kharkiv, Ukraine
Communal Institution of Lviv Regional Council 'Lypa Lviv Regional Hospital'
🇺🇦Lviv-Vynnyky, Ukraine
Vinnytsya Regional Clinical Hospital named after M.I.Pirogov
🇺🇦Vinnytsia, Ukraine
Regional Hospital of Liepaja
🇱🇻Liepaja, Latvia
CSK UM Klinika Ortopedii
🇵🇱Lodz, Poland
Oddzial Urazowo-Ortopedyczny Wojewodzki Szpital Specjalistyczny
🇵🇱Lublin, Poland
Klinika Ortopedii I Traumatologii,Szpital Kliniczny Ortopedyczno-Rehabilitacyjny UM
🇵🇱Poznan, Poland
University Malaya Medical Center
🇲🇾Kuala Lumpur, Malaysia
SP ZOZ MSWiA w Krakowie Oddzial Urazowo-Ortopedyczny
🇵🇱Krakow, Poland
Oddzial Ortopedii i Traumatologii Szpital Specjalistyczny im. L.Rydygiera
🇵🇱Krakow, Poland
Vidzemes Hospital
🇱🇻Valmiera, Latvia
Institute of Spine and JointPathology named after Prof.Sytenko of NationalAcademy of MedicalSciences
🇺🇦Kharkiv, Ukraine
Ivano-Frankivsk Regional Clinical Hospital
🇺🇦Ivano-Frankivsk, Ukraine
Kyiv Regional Clinical Hospital
🇺🇦Kyiv, Ukraine
Zaporizhzhia Regional Clinical Hospital
🇺🇦Zaporizhzhia, Ukraine
Arizona Research Center
🇺🇸Phoenix, Arizona, United States