VTE Prophylaxis With Anticoagulation After Total Knee Replacement Surgery Clinical Trial
— TEXT-TKROfficial title:
A Randomized, Double-blind, Double-dummy, Multicenter, Adaptive Design, Dose Escalation (Part 1) and Dose-Response (Part 2) Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement Surgery
| Verified date | November 2019 |
| Source | Janssen Research & Development, LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Completed |
| Enrollment | 308 |
| Est. completion date | November 5, 2018 |
| Est. primary completion date | November 5, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 50 Years and older |
| Eligibility |
Inclusion Criteria: - 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 Exclusion Criteria: - 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 |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Clínica Adventista Belgrano | Caba | |
| Argentina | Hospital Italiano de Buenos Aires | Caba | |
| Argentina | Clínica Chutro | Córdoba | |
| Argentina | Hospital San Roque | Córdoba | |
| Argentina | Hospital Italiano La Plata | La Plata | |
| Argentina | Sanatorio Britanico de Rosario | Rosario | |
| Argentina | Sanatorio San Miguel | San Miguel | |
| Belgium | ZNA Middelheim | Antwerpen | |
| Belgium | Ziekenhuis Oost-Limburg | Genk | |
| Belgium | Jessa Ziekenhuis | Hasselt | |
| Belgium | ZNA Jan Palfijn | Merksem | |
| Brazil | Hospital Sao Francisco de Assis | Belo Horizonte | |
| Brazil | Universidade Federal de Minas Gerais (UFMG) - Faculdade de Medicina | Belo Horizonte | |
| Brazil | Unicamp - Hospital de Clinicas | Campinas | |
| Brazil | Uniort.e - Hospital de ortopedia | Londrina | |
| Brazil | Irmandade da Santa Casa de Misericórdia de Marília | Marilia | |
| Brazil | Santa Casa de Misericordia de Porto Alegre | Porto Alegre | |
| Brazil | Hospital e Maternidade Dr Christovão da Gama | Santo André | |
| Brazil | Hospital Estadual Mario covas | Santo André | |
| Brazil | Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo | São Paulo | |
| Bulgaria | Multiprofile Hospital for Active Treatment Russe | Russe | |
| Bulgaria | Acibadem City Clinic Tokuda Hospital | Sofa | |
| Bulgaria | Military Medical Academy | Sofia | |
| Canada | Lakeridge Health Ajax | Ajax | Ontario |
| Canada | Source Trial Solutions Inc. | Kitchener | Ontario |
| Canada | The Ottawa Hospital Research Institute | Ottawa | Ontario |
| Italy | Azienda Ospedaliera Papa Giovanni XXIII | Bergamo | |
| Italy | Cliniche Humanitas Gavazzeni | Bergamo | |
| Italy | Istituto Ortopedico Rizzoli | Bologna | |
| Italy | Azienda Ospedaliera Universitaria Careggi | Firenze | |
| Italy | Istituto Clinico Humanitas | Rozzano | |
| Italy | IRCCS Policlinico San Donato | S. Donato Milanese | |
| Italy | A.O.U. Città della Salute e della Scienza | Torino | |
| Italy | Ospedale Mauriziano (Torino) | Torino | |
| Japan | Matsudo City General Hospital | Chiba | |
| Japan | Hakodate Goryokaku Hospital | Hakodate | |
| Japan | Ritsuzankai Iida Hospital | Iida-shi | |
| Japan | Itami City Hospital | Itami-shi | |
| Japan | Yonemori Hospital | Kagoshima-shi | |
| Japan | Bange Kousei General Hospital | Kawanuma-Gun | |
| Japan | Osaka Rosai Hospital | Osaka | |
| Japan | Osaka Saiseikai Nakatsu Hospital | Osaka-shi | |
| Japan | Tokushima Municipal Hospital | Tokushima-shi | |
| Japan | Yuaikai Tomishiro Central Hospital | Tomishiro | |
| Latvia | Regional Hospital of Liepaja | Liepaja | |
| Latvia | Hospital of Traumatology and Orthopedics | Riga | |
| Latvia | Riga 2nd Hospital | Riga | |
| Latvia | Vidzemes Hospital | Valmiera | |
| Lithuania | Hospital of Lithuanian University of Health Sciences Kaunas Clinics | Kaunas | |
| Lithuania | Klaipeda University Hospital | Klaipeda | |
| Malaysia | University Malaya Medical Center | Kuala Lumpur | |
| Malaysia | Hospital Tengku Ampuan Afzan | Kuantan | |
| Malaysia | Hospital Miri | Miri | |
| Malaysia | Hospital Sibu | Sibu | |
| Malaysia | Hospital Sultan Abdul Halim | Sungai Petani | |
| Poland | Klinika Ortopedii i Traumatologii UMB | Bialystok | |
| Poland | Oddzial Ortopedii i Traumatologii - Szpital Ogolny im. W.Ginela | Grajewo | |
| Poland | Klinika Ortopedii Gornoslaskie Centrum Medyczne | Katowice | |
| Poland | Oddzial Ortopedii i Traumatologii Szpital Specjalistyczny im. L.Rydygiera | Krakow | |
| Poland | SP ZOZ MSWiA w Krakowie Oddzial Urazowo-Ortopedyczny | Krakow | |
| Poland | 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 | Oddzial Ortopedii Specjalistyczny Szpital im. E.Szczeklika | Tarnow | |
| Poland | Oddzial Chirurgii Urazowej iOrtopedycznej,Wojewodzki Szpital Brodnowski, SPZOZ | Warszawa | |
| Russian Federation | Barnaul Federal Center of Traumatology, Orthopedics and Endoprothesis replacement | Barnaul | |
| Russian Federation | Russian Ilizarov Scientific Center For Restorative Traumatology And Ortopaedics | Kurgan | |
| Russian Federation | Moscow City Clinical Hospital #1 n.a. N.I.Pirogov | Moscow | |
| Russian Federation | Privolzhsky Research Medical University of Ministry of Health of Russian Federation | Nizhny Novgorod | |
| Russian Federation | Russian Research Institute of Traumatology and Orthopaedics n.a.R.R.Vreden | Saint-Petersburg | |
| Russian Federation | St. Petersburg State Medical Institution City Multifunctional Hospital #2 | Saint-Petersburg | |
| Russian Federation | State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin | Samara | |
| Russian Federation | Clinical Emergency Hospital n.a. N.V. Solovyev | Yaroslavl | |
| Spain | Hosp. Univ. Germans Trias I Pujol | Badalona | |
| Spain | Hosp. Clinico San Carlos | Madrid | |
| Spain | 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 | |
| Turkey | Ankara Numune Research and Training Hospital | Ankara | |
| Turkey | Diskapi Yildirim Beyazid Training and Research Hospital | Ankara | |
| Turkey | Yildirim Beyazit University Medical Faculty Ankara Atatürk Research and Training Hospital | Ankara | |
| Turkey | Yildirim Beyazit University Yenimahalle Training and Research Hospital | Ankara | |
| Turkey | Bakirkoy Training and Research Hospital | Istanbul | |
| Turkey | Umraniye Training and Research Hospital | Istanbul | |
| Turkey | Izmir Tepecik Training and Research Hospital | Izmir | |
| Ukraine | Municipal Institution Cherkasy Regional Hospital of Cherkasy Regional Council | Cherkasy | |
| Ukraine | Ivano-Frankivsk Regional Clinical Hospital | Ivano-Frankivsk | |
| Ukraine | Institute of Spine and JointPathology named after Prof.Sytenko of NationalAcademy of MedicalSciences | Kharkiv | |
| Ukraine | Municipal Institution of Health Care 'Kharkiv Regional Clinical Traumatology Hospital' | Kharkiv | |
| Ukraine | Kyiv Regional Clinical Hospital | Kyiv | |
| 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 | Zaporizhzhia Regional Clinical Hospital | Zaporizhzhia | |
| United States | Florida Research Associates, LLC | DeLand | Florida |
| United States | Denver Metro Orthopedics, PC | Englewood | Colorado |
| United States | Memorial Hermann Memorial City Medical Center | Houston | Texas |
| United States | Avanza research | Pensacola | Florida |
| United States | Arizona Research Center | Phoenix | Arizona |
| United States | University Orthopedic and Joint Replacement Center | Tamarac | Florida |
| United States | Harbor-UCLA Medical Center | Torrance | California |
| Lead Sponsor | Collaborator |
|---|---|
| Janssen Research & Development, LLC |
United States, Argentina, Belgium, Brazil, Bulgaria, Canada, Italy, Japan, Latvia, Lithuania, Malaysia, Poland, Russian Federation, Spain, Turkey, Ukraine,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) | |
| Primary | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Major Bleeding Event (CEC-adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated) | 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. | Up to Day 10 and 14 (visit observation period) | |
| Secondary | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Major VTE (CEC-adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | Number of participants with nonfatal PE (adjudicated by CEC) were reported. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Death (CEC-adjudicated) | Number of participants with death (adjudicated by CEC) were reported. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) | |
| Secondary | Number of Participants With Distal DVT (CEC-adjudicated) | 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. | Up to Day 10 to 14 (visit observation period) |