A Study of JNJ-70033093 (BMS-986177) Versus Subcutaneous Enoxaparin in Participants Undergoing Elective Total Knee Replacement Surgery
- Conditions
- Arthroplasty, Replacement, Knee
- Interventions
- Drug: JNJ-70033093 200 mgDrug: JNJ-70033093 50 mgDrug: JNJ-70033093 25 mgDrug: JNJ-70033093 100 mgDrug: Enoxaparin 40 mgDrug: Placebo
- Registration Number
- NCT03891524
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
- Detailed Description
JNJ-70033093 is an oral anticoagulant for prevention and treatment of thromboembolic events (for example, VTE) that binds and inhibits activated form of human coagulation Factor XI (FXIa) with high affinity and selectivity. The study will consist of 3 phases: up to 30-day screening phase before total knee replacement (TKR) surgery, 10 to14 day postoperative dosing phase, and 4-week follow-up phase. The hypothesis of this study is JNJ-70033093 reduces risk of total VTE during treatment period. The total duration of participation following randomization will be approximately 6 weeks. Efficacy evaluations include unilateral venography assessment of operated leg and assessments of symptomatic DVT, PE, or death. Safety evaluation includes adverse events, clinical laboratory tests, and physical examinations. The safety and efficacy will be monitored throughout the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1242
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A: JNJ-70033093 25 mg + Placebo BID Placebo Participants 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 F: JNJ-70033093 200 mg Once Daily + Placebo Placebo Participants 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 D: JNJ-70033093 200 mg BID JNJ-70033093 200 mg Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID orally for 10 to 14 postoperative days. Group G: JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 50 mg Participants 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 A: JNJ-70033093 25 mg + Placebo BID JNJ-70033093 25 mg Participants 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 C: JNJ-70033093 100 mg + Placebo BID JNJ-70033093 100 mg Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days. Group C: JNJ-70033093 100 mg + Placebo BID Placebo Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days. Group E: JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 25 mg Participants 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 E: JNJ-70033093 25 mg Once Daily + Placebo Placebo Participants 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 JNJ-70033093 200 mg Participants 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 B: JNJ-70033093 50 mg BID JNJ-70033093 50 mg Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days. Group G: JNJ-70033093 50 mg once daily + Placebo Placebo Participants 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 Enoxaparin 40 mg Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
- Primary Outcome Measures
Name Time Method Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) Up to Day 14 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.
- Secondary Outcome Measures
Name Time Method Impact of Selected Demographic: Age on CL/F Up to Day 14 Impact of age on CL/F was assessed.
Impact of Selected Demographic: Weight on CL/F Up to Day 14 Impact of weight on CL/F was assessed.
Number of Participants With Any Bleeding Event (CEC-adjudicated) Up to Day 14; Up to Day 52 Any bleeding was defined as the composite of major bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) criteria modified for the surgical setting, clinically relevant nonmajor bleeding events, or minimal bleeding events as assessed by the CEC.
Number of Participants With Total VTE (CEC-adjudicated) Up to Day 52 Total VTE was defined as the composite of (CEC-adjudicated) proximal and/or DVT (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal PE, or any death.
Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) Up to Day 14, Up to Day 52 Composite of Major bleeding event (BE): 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, deep wound infection and/or either 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 is still considered clinically relevant for example: Epistaxis, Gastrointestinal bleed,Hematuria,Bruising/ecchymosis,Hemoptysis,Hematoma.
Number of Participants With Major Bleeding Events (CEC-adjudicated) Up to Day 14; Up to Day 52 Number of participants with major BE (adjudicated by CEC) were reported. Major Bleeding events were defined as: 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; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability.
Number of Participants With CRNM Bleeding Events (CEC-adjudicated) Up to Day 14; Up to Day 52 Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
Number of Participants With Minimal Bleeding Events (CEC-adjudicated) Up to Day 14; Up to Day 52 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. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) Up to Day 14; Up to Day 52 Major Bleeding events were defined as: 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; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either 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 is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
Number of Participants With Major VTE (CEC-adjudicated) Up to Day 14 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.
Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) Up to Day 14 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.
Number of Participants With Proximal DVT (CEC-adjudicated) Up to Day 52 Number of participants with proximal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Number of Participants With Distal DVT (CEC-adjudicated) Up to Day 52 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.
Impact of Selected Laboratory Values: Renal Function on CL/F Up to Day 14 Impact of renal function on CL/F was assessed. The outcome measure was reported based on CRCL.
Impact of Selected Demographics: Sex on Apparent Volume of Distribution (V/F) Up to Day 14 Impact of sex on V/F was assessed.
Impact of Selected Demographics : Age on V/F Up to Day 14 Impact of age on V/F was assessed.
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) Up to Day 52 Number of participants with nonfatal PE (adjudicated by CEC) were reported.
Number of Participants With Deaths (CEC-adjudicated) Up to Day 52 Number of participants with deaths (CEC-adjudicated) were reported.
Apparent Clearance (CL/F) of JNJ-70033093 Up to Day 14 Apparent clearance of a drug was defined as a measure of the rate at which a drug got metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Apparent Volume of Distribution (V/F) of JNJ-70033093 Up to Day 14 V/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.
Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex Up to Day 14 Impact of demographic character (sex) on CL/F was assessed.
Impact of Selected Demographics : Weight on V/F Up to Day 14 Impact of weight on V/F was assessed.
Impact of Selected Laboratory Values: Renal Function on V/F Up to Day 14 Impact of renal function on V/F was assessed. The outcome measure is reported based on CRCL.
Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach Up to 14 days The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate.
Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach Up to 14 days The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate.
Trial Locations
- Locations (117)
Ziekenhuis Oost-Limburg
🇧🇪Genk, Belgium
Somogy Megyei Kaposi Mor Oktato Korhaz
🇭🇺Kaposvar, Hungary
Clínica Adventista Belgrano
🇦🇷Caba, Argentina
University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski
🇧🇬Pleven, Bulgaria
Centro Hospitalar do Baixo Vouga - Hospital Infante Dom Pedro
🇵🇹Aveiro, Portugal
Privolzhsky Regional Medical Center of Federal Medical and Biological Agency
🇷🇺Nizhniy Novgorod, Russian Federation
Communal Institution of Lviv Regional Council 'Lypa Lviv Regional Hospital'
🇺🇦Lviv-Vynnyky, Ukraine
Private Healthcare Institution 'Clinical Hospital 'RZD-Medcine' n.a. N.A.Semashko'
🇷🇺Moscow, Russian Federation
Instituto de Investigaciones Clinicas Rosario
🇦🇷Rosario, Argentina
ZNA Jan Palfijn
🇧🇪Merksem, Belgium
University General Hospital of Rio Patras
🇬🇷Patra, Greece
Fejer Megyei Szent Gyorgy Egyetemi Oktatokorhaz
🇭🇺Szekesfehervar, Hungary
Kaplan Medical Center
🇮🇱Rehovot, Israel
Sanatorio Corporación Médica de General San Martín
🇦🇷San Martín, Argentina
ZNA Middelheim
🇧🇪Antwerpen, Belgium
Acibadem City Clinic Tokuda Hospital
🇧🇬Sofa, Bulgaria
General Hospital of Nea Ionia 'Konstantopoulio'
🇬🇷Nea Ionia, Greece
Petz Aladar Megyei Oktato Korhaz
🇭🇺Gyõr, Hungary
General Hospital of Attiki 'KAT'
🇬🇷Kifisia, Greece
Saitama City Hospital
🇯🇵Saitama-shi, Japan
Japan Community Health Care Organization Saitama Medical Center
🇯🇵Saitama, Japan
Szpital Ogolny im. W. Ginela, Oddzial Urazowo-Ortopedyczny
🇵🇱Grajewo, Poland
CSK UM Klinika Ortopedii
🇵🇱Lodz, Poland
Oddzial Urazowo-Ortopedyczny Wojewodzki Szpital Specjalistyczny
🇵🇱Lublin, Poland
ULSAM, EPE - Hospital de Santa Luzia
🇵🇹Viana do Castelo, Portugal
Oddzial Ortopedii Specjalistyczny Szpital im. E.Szczeklika
🇵🇱Tarnow, Poland
CHS - Hosp. Orto. Sant'Iago do Outao
🇵🇹Setubal, Portugal
Hosp. de Cascais
🇵🇹Cascais, Portugal
Municipal Institution of Health Care 'Kharkiv Regional Clinical Traumatology Hospital'
🇺🇦Kharkiv, Ukraine
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Central Research Associates, Inc.
🇺🇸Birmingham, Alabama, United States
Arizona Research Center
🇺🇸Phoenix, Arizona, United States
University Orthopedic and Joint Replacement Center
🇺🇸Tamarac, Florida, United States
Denver Metro Orthopedics, PC
🇺🇸Englewood, Colorado, United States
Bowen Hefley Orthopedics
🇺🇸Little Rock, Arkansas, United States
Clínica Chutro
🇦🇷Córdoba, Argentina
Hospital Italiano La Plata
🇦🇷La Plata, Argentina
DMI Research
🇺🇸Pinellas Park, Florida, United States
Medical Investigative and Clinical Evaluation Inc
🇨🇦Windsor, Ontario, Canada
Gulfcoast Research Institute
🇺🇸Sarasota, Florida, United States
Hospital Britanico de Buenos Aires
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Hospital San Roque
🇦🇷Córdoba, Argentina
Memorial Hermann Memorial City Medical Center
🇺🇸Houston, Texas, United States
Hospital e Maternidade Dr Christovão da Gama
🇧🇷Santo André, Brazil
Hospital Estadual Mario covas
🇧🇷Santo André, Brazil
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
Hospital Sao Francisco de Assis
🇧🇷Belo Horizonte, Brazil
University Multiprofile Hospital Sofiamed Sofia
🇧🇬Sofia, Bulgaria
Lakeridge Health
🇨🇦Ajax, Ontario, Canada
The Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Hamilton Health Sciences Corporation
🇨🇦Hamilton, Ontario, Canada
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Papageorgiou General Hospital
🇬🇷Thessaloniki, Greece
Debreceni Egyetem
🇭🇺Debrecen, Hungary
Bacs-kiskun Megyei Korhaz
🇭🇺Kecskemét, Hungary
Rambam Medical Center
🇮🇱Haifa, Israel
Szegedi Tudomanyegyetem
🇭🇺Szeged, Hungary
Carmel Medical Center
🇮🇱Haifa, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
Cliniche Humanitas Gavazzeni
🇮🇹Bergamo, Italy
Azienda Ospedaliera Papa Giovanni XXIII
🇮🇹Bergamo, Italy
MAV Korhaz es Rendelointezet
🇭🇺Szolnok, Hungary
Policlinico S. Matteo
🇮🇹Pavia, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
A.O.U. Città della Salute e della Scienza
🇮🇹Torino, Italy
Matsudo City General Hospital
🇯🇵Chiba, Japan
Japanese Red Cross Hamamatsu Hospital
🇯🇵Hamamatsu, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama, Japan
Hakodate Goryokaku Hospital
🇯🇵Hakodate, Japan
Oddzial Chirurgii Urazowej iOrtopedycznej,Wojewodzki Szpital Brodnowski, SPZOZ
🇵🇱Warszawa, Poland
Yonemori Hospital
🇯🇵Kagoshima-shi, Japan
Japan Community Health care Organization Kyushu Hospital
🇯🇵Kitakyushu-shi,, Japan
Chubu Rosai Hospital
🇯🇵Nagoya, Japan
Juntendo University Nerima Hospital
🇯🇵Nerima-Ku, Japan
Yuuai Medical Center
🇯🇵Okinawa, Tomigusuku-shi, Japan
Itami City Hospital
🇯🇵Itami-shi, Japan
Marunouchi Hospital
🇯🇵Matsumoto, Japan
Nagano Prefectural Shinshu Medical Center
🇯🇵Suzaka, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Bielsku Podlaskim,Oddział Urazowo-Ortopedyczny
🇵🇱Bielsk Podlaski, Poland
Wojewodzki Szpital Zespolony w Kielcach, Klinika Chirurgii Ortopedyczno-Urazowej
🇵🇱Kielce, Poland
Oddzial Ortopedii i Traumatologii Narzadu Ruchu Szpital Specjalistyczny im. Ludwika Rydygiera
🇵🇱Krakow, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
🇵🇱Wroclaw, Poland
National medical research center of Traumatology and Orthopaedics n.a. R.R.Vreden
🇷🇺Saint-Petersburg, Russian Federation
H. Santo António - Centro Hospitalar do Porto
🇵🇹Porto, Portugal
National Medical Research Center of Traumatology and Orthopaedics n.a. G.A. Ilizarov
🇷🇺Kurgan, Russian Federation
Steve Biko Academic Hospital
🇿🇦Pretoria, South Africa
Hosp. Univ. Germans Trias I Pujol
🇪🇸Badalona, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin
🇷🇺Samara, Russian Federation
Adana City Hospital
🇹🇷Adana, Turkey
Hosp. Clinico Univ. de Valencia
🇪🇸Valencia, Spain
Hosp. Univ. Vall D Hebron
🇪🇸Barcelona, Spain
Smolensk Federal Center of Traumatology, Orthopedics and Endoprothesis Replacement
🇷🇺Smolensk, Russian Federation
Sochi City Hospital #4
🇷🇺Sochi, Russian Federation
Hosp. Clinic I Provincial de Barcelona
🇪🇸Barcelona, Spain
Hosp. Univ. de Bellvitge
🇪🇸Barcelona, Spain
Clinical Project Research SA
🇿🇦Worcester, South Africa
Hosp. Univ. Fundacion Alcorcon
🇪🇸Alcorcón, Spain
Complejo Hospitalario de Jaen
🇪🇸Jaen, Spain
Corporacio Sanitari Parc Tauli
🇪🇸Sabadell, Spain
Dışkapı Yıldırım Beyazıd Training and Research Hospital
🇹🇷Ankara, Turkey
Yıldırım Beyazıt University Yenimahalle Training and Research Hospital
🇹🇷Ankara, Turkey
Bakirkoy Training and Research Hospital
🇹🇷Istanbul, Turkey
Antalya Training And Research Hospital
🇹🇷Antalya, Turkey
Şişli Etfal Research Training Hospital
🇹🇷Istanbul, Turkey
Kyiv Regional Clinical Hospital
🇺🇦Kyiv, Ukraine
Izmir Tepecik Training and Research Hospital
🇹🇷Izmir, Turkey
Ivano-Frankivsk Regional Clinical Hospital
🇺🇦Ivano-Frankivsk, Ukraine
Institute of Spine and JointPathology named after Prof.Sytenko of NationalAcademy of MedicalSciences
🇺🇦Kharkiv, Ukraine
Vinnytsya Regional Clinical Hospital named after M.I.Pirogov
🇺🇦Vinnytsia, Ukraine
Municipal Non-profit Enterprise 'Odesa Regional Clinical Hospital' Odesa Regional Council
🇺🇦Odesa, Ukraine
Hosp. Univ. I Politecni La Fe
🇪🇸Valencia, Spain
MHAT Tzaritza Joanna
🇧🇬Sofia, Bulgaria
Medical Center - Medical Complex BEROE EOOD
🇧🇬Stara Zagora, Bulgaria
Istituto Ortopedico Rizzoli
🇮🇹Bologna, Italy