BIBR 1048 Dose Range Finding Study in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip or Knee Replacement Surgery
- Registration Number
- NCT01225822
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this study is to establish the dose-response relationship with regard to efficacy and safety of BIBR 1048 (50 mg bis in die(b.i.d), 150 mg b.i.d, 225 mg b.i.d. and 300 mg quaque die(q.d) ) in preventing venous thromboembolism(VTE) in patients undergoing primary elective total hip and knee replacement.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1973
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIBR 1048 50 mg bis in die(b.i.d) BIBR 1048 BIBR 1048 50 mg b.i.d twice a day plus two capsules of placebo matching BIBR 1048 0 mg twice a day plus one placebo matching enoxaparin 0 mg once a day for the treatment period BIBR 1048 150 mg b.i.d BIBR 1048 BIBR 1048 150 mg b.i.d twice a day plus two capsules of placebo matching BIBR 1048 0 mg twice a day plus placebo matching enoxaparin 0 mg once a day for the treatment period Enoxaparin 40 mg subcutaneous(s.c) Enoxaparin placebo matching BIBR 1048 0 mg twice a day plus enoxaparin 40 mg s.c once a day for the treatment period BIBR 1048 225 mg b.i.d BIBR 1048 BIBR 1048 225 mg b.i.d twice a day plus two capsules of placebo matching BIBR 1048 0 mg twice a day plus placebo matching enoxaparin 0 mg once a day for the treatment period BIBR 1048 300 mg quaque die(q.d) BIBR 1048 BIBR 1048 150 mg q.d once a day plus placebo matching BIBR 1048 0 mg twice a day plus placebo matching enoxaparin 0 mg once a day for the treatment period
- Primary Outcome Measures
Name Time Method Number of Participants With Venous Thromboembolic (VTE) Events Treatment period (up to day 8+/-2 days visit) Deep vein thrombosis (DVT) (proximal and distal) as detected by routine bilateral venography on day 8 +/- 2, plus symptomatic DVT confirmed by venography during the treatment period or PE confirmed by objective testing
Number of Participants With Major Bleeding Events (MBE) From approximately 14 days prior to surgery to 4-6 weeks post surgery
- Secondary Outcome Measures
Name Time Method Number of Participants With VTE Events and All Cause Mortality Treatment period (up to day 8+/-2 days visit) Deep venous thrombosis (DVT) (proximal and distal) as detected by routine bilateral venography on day 8 +/- 2, plus symptomatic DVT confirmed by venography during the treatment period or Pulmonary Embolism (PE) confirmed by objective testing and all deaths.
Number of Participants With Proximal DVT, PE (Pulmonary Embolism) and VTE Related Mortality Treatment period (up to day 10) Deep venous thrombosis (DVT) (proximal) as detected by routine bilateral venography on day 8 +/- 2, plus symptomatic proximal DVT confirmed by venography during the treatment period or PE confirmed by objective testing plus VTE related mortality
Number of Participants With Proximal DVT Treatment period (up to day 8+/-2 days visit) Deep venous thrombosis (DVT) (proximal) as detected by routine bilateral venography on day 8 +/- 2, plus symptomatic proximal DVT confirmed by venography during the treatment period
Volume of Blood Loss Day 1 (Day of surgery) Volume of blood loss was to be analysed using an analysis of variance (ANOVA), which included treatment and centre.
Rate of Transfusions Due to Bleedings Day 1 (Day of surgery) Percentage of patients requiring transfusions due to bleeding .Rate of need of transfusion were to be analysed using a logistic regression with treatment and centre.
Number of Participants With Clinically Significant, Minor or Any Bleeding Events Treatment period (up to day 8+/-2 days visit) Number of participants with Clinically Significant, minor or any bleeding events. Clinically significant bleeding events are defined as
* Spontaneous skin haematoma larger than \>25 cm²
* Wound haematoma \>100 cm²
* Spontaneous nose bleed \>5 minutes
* Macroscopic haematurea, either spontaneous or lasting more than 24 hours if associated with an intervention
* Spontaneous rectal bleeding (more than spot on toilet paper)
* Gingival bleeding \>5 minutes
* Any other bleeding event considered as clinically significant by the investigator All other bleeding events that did not fulfil the criteria of MBE or clinically significant bleeding event were classified as minor bleeding events.Laboratory Analyses Screening to end of treatment Number of patients with possible clinically significant abnormalities, i.e. with values out of normal range.
Normal ranges are defined as:
Haematocrit \[%\]: (0.35-0.45) for women and (0.39-0.51) for men Haemoglobin \[g/dL\]: (11.6-15.4) for women and (13.2-17.3) for men White Blood Cell count \[10\^9/L\]: (4-10.3) for women and (3.9-10.3) for men Platelets \[10\^9/L\]: (145-420) for women and men Sodium \[mmol/L\]: (135-146) for women and men Potassium \[mmol/L\]: (3.5-5) for women and men Aspartate aminotransferase (AST) \[U/L\]: (11-37) for women and (11-39) for men Alanine aminotransferase (ALT) \[U/L\]: (8-43) for women and (8-45) for men Alkaline Phosphatase \[U/L\]: (36-118) for women and (35-123) for men Creatinine \[mg/dL\]: (0.57-1.06)for women and (0.72-1.3) for men Bilirubin, total \[mg/dL\]: (0.22-1.28) for women and men Uric acid \[mg/dL\]: (2.4-6.47) for women and menPlasma Concentration (Cmax) of Dabigatran Day 1 to end of treatment Maximum plasma concentration of Dabigatran (at steady-state) and Pre-dose plasma concentrations at steady state.
Cmax represents the maximum concentration of Dabigatran in plasma. Cmax,ss represents the maximum concentration of Dabigatran in plasma at steady state.
Cpre,ss represents pre-dose concentration of Dabigatran in plasma at steady stateArea Under the Plasma Concentration-time Curve During a Dosing Interval up to day 8+/-2 days visit Area under the plasma concentration-time curve during a dosing interval (at steady-state). The AUC0-12h (for b.i.d. treatment regimens) and AUC0-24h (300 mg q.d.) after the first dose on day of surgery calculated by extrapolation using the elimination rate constant, reported only if the extrapolated fraction of AUC was less than 30 % of the total AUC.
Trial Locations
- Locations (59)
1160.19.43001 A.ö. Krankenhaus d. Statutarstadt Wiener Neustadt
🇦🇹Wr. Neustadt, Austria
1160.19.42006 Hospital Mlada Boleslav
🇨🇿Mlada Boleslav, Czech Republic
1160.19.32005 Virga Jesseziekenhuis
🇧🇪Gent, Belgium
1160.19.32002 V.U.B. Jette
🇧🇪Brussel, Belgium
1160.19.43004 Krankenhaus der Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
1160.19.32006 Boehringer Ingelheim Investigational Site
🇧🇪Huy, Belgium
1160.19.42004 University Hospital Brno
🇨🇿Brno-Bohunice, Czech Republic
1160.19.42003 University Hospital Ostrava
🇨🇿Ostrava, Czech Republic
1160.19.45042 Orthopedic Surgical Clinic
🇩🇰Frederiksberg, Denmark
1160.19.45045 Gentofte Hospital
🇩🇰Hellerup, Denmark
1160.19.45043 Herlev Hospital
🇩🇰Herlev, Denmark
1160.19.45041 Hørsholm Sygehus
🇩🇰Hørsholm, Denmark
1160.19.45044 Orthopedic Surgical Dept.
🇩🇰Silkeborg, Denmark
1160.19.46003 Ortopediska kliniken, Länssjukhuset i Kalmar
🇸🇪Kalmar, Sweden
1160.19.43002 Orthopädisches Spital Speising
🇦🇹Wien, Austria
1160.19.32007 C.H.U. de Tivoli
🇧🇪La Louvière, Belgium
1160.19.32004 UZ Gent
🇧🇪Gent, Belgium
1160.19.42001 Hospital Kladno
🇨🇿Kladno, Czech Republic
1160.19.42009 University Hospital Na Bulovce
🇨🇿Prague 8, Czech Republic
1160.19.42005 University Hospital Plzen
🇨🇿Plzen, Czech Republic
1160.19.35802 Keski-Suomen keskussairaala
🇫🇮Jyväskylä, Finland
1160.19.35801 Oulun yliopistollinen sairaala, Leikkaus- ja tehohoidon yks.
🇫🇮Oulu, Finland
1160.19.33007 Clinique du Mail
🇫🇷La Rochelle, France
1160.19.33004 Div
🇫🇷Illkirch cedex, France
1160.19.33009 Hôpital Edouard Herriot
🇫🇷Lyon cedex 03, France
1160.19.36003 Sándor Péterfy Hospital
🇭🇺Budapest, Hungary
1160.19.33006 Clinique Mutualiste
🇫🇷Saint-Etienne cedex 2, France
1160.19.33008 Clinique de l'Atlantique
🇫🇷St Herblain cedex, France
1160.19.36001 Kálmán Pándy County Hospital
🇭🇺Gyula, Hungary
1160.19.36005 Szent György Hospital
🇭🇺Székesfehérvár, Hungary
1160.19.36004 Bács-Kiskun County Hospital
🇭🇺Kecskemét, Hungary
1160.19.39004 Ospedale di Circolo di Varese
🇮🇹Varese, Italy
1160.19.36002 Albert Szent-Györgyi Medical and Pharmacological Center
🇭🇺Szeged, Hungary
1160.19.39005 Modulo Coordinazione Dipartimentale di Ricerca e Anestesia
🇮🇹Bologna, Italy
1160.19.39003 U. O. Ortopedia e Traumatologia
🇮🇹Bergamo, Italy
1160.19.39002 Fondazione Centro S. Raffaele
🇮🇹Milano, Italy
1160.19.31001 Boehringer Ingelheim Investigational Site
🇳🇱Amsterdam, Netherlands
1160.19.39001 IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
1160.19.31003 Boehringer Ingelheim Investigational Site
🇳🇱Hilversum, Netherlands
1160.19.31005 Hengstdal 3
🇳🇱Nijmegen, Netherlands
1160.19.47001 Nordlandssykehuset HF, Bodø
🇳🇴Bodø, Norway
1160.19.31006 Boehringer Ingelheim Investigational Site
🇳🇱Sittard, Netherlands
1160.19.31004 Boehringer Ingelheim Investigational Site
🇳🇱Zwolle, Netherlands
1160.19.47004 Martina Hansens Hospital
🇳🇴Bærum Postterminal, Norway
1160.19.47008 Martina Hansens Hospital
🇳🇴Bærum Postterminal, Norway
1160.19.47007 Sykehuset Innlandet HF, Avd. Elverum
🇳🇴Elverum, Norway
1160.19.27001 Dept. of Haematology
🇿🇦Johannesburg, South Africa
1160.19.46007 Kungälvs sjukhus
🇸🇪Kungälvs, Sweden
1160.19.47005 Haugesund sjukehus HF
🇳🇴Haugesund, Norway
1160.19.47002 Sykehuset Telemark HF, Avd. Skien
🇳🇴Skien, Norway
1160.19.47003 Helse Sunnmøre HF, Ålesund sykehus
🇳🇴Ålesund, Norway
1160.19.46002 Kirurgavdelningen
🇸🇪Falköping, Sweden
1160.19.46001
🇸🇪Göteborg, Sweden
1160.19.27002 Suite 203
🇿🇦Johannesburg, South Africa
1160.19.46004 Ortopediska kliniken, Länssjukhuset, Halmstad
🇸🇪Halmstad, Sweden
1160.19.46008 Ortopediska Institutionen
🇸🇪Linköping, Sweden
1160.19.46005 Kirurg Ortopediska kliniken, Sjukhuset i Lidköping
🇸🇪Lidköping, Sweden
1160.19.46009 Sahlgrenska Universitetssjukhuset, Mölndal
🇸🇪Mölndal, Sweden
1160.19.46006 Boehringer Ingelheim Investigational Site
🇸🇪Varberg, Sweden