BIBR 1048 Dose Range Finding Study in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip or Knee Replacement Surgery

Venous Thromboembolism Clinical Trial

Official title:

BIBR 1048 Dose Range Finding Study in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip or Knee Replacement Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01225822
• Other study ID #: 1160.19
• Status: Completed
• Phase: Phase 2
• First received: October 20, 2010
• Last updated: May 8, 2014
• Start date: November 2002

Study information

• Verified date: February 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria:Belgium:Czech Republic:Denmark:Finland:France:Hungary:Italy: Ethics CommitteeNetherlands:Norway:South Africa:Sweden:
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1973
• Est. primary completion date: August 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria

1. Patients scheduled to undergo a primary elective total hip or knee replacement.

2. Male of female being 18 years or older.

3. Patients weighing at least 40 kg.

4. Written informed consent for study participation.

Exclusion criteria

1. Bleeding diathesis, constitutional or acquired coagulation disorders.

2. Major surgery or trauma(e.g., hip fracture) within the last 3 months.

3. Cardiovascular disease

4. Any history of haemorrhagic stroke, intracranial or intraocular bleeding or cerebral ischaemic attacks lasting more than 24 hours and / or with cardiovascular pathological findings.

5. Deep vein thrombosis(DVT), gastrointestinal or pulmonary bleeding, gastric or duodenal ulcer within the last year.

6. History of or acute intracranial disease

7. Liver disease

8. Renal disease

9. Use of long-term anticoagulants or antiplatelet drugs within 7 days prior to hip/knee replacement operation.

10. Pre-menopausal women who are not surgically steriles, are nursing and are of child-bearing potential and are not practising acceptable methods of birth control

11. Known allergy to contrast media

12. Thrombocytopenia

13. Allergy against heparin.

14. Active malignant disease or current cytostatic treatment.

15. Treatment with an investigational drug in the past month.

16. Leg amputee

17. Known alcohol or drug abuse

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Enoxaparin
Enoxaparin 40 mg s.c once a day for 5-10 days of treatment period
• BIBR 1048
50 mg b.i.d BIBR 1048 capsule twice a day for 5-10 days of treatment period
• BIBR 1048
150 mg b.i.d BIBR 1048 capsule twice a day for 5-10 treatment period
• BIBR 1048
225 mg b.i.d BIBR 1048 capsule twice a day for 5-10 treatment period
• BIBR 1048
300 mg q.d BIBR 1048 capsule for 5-10 treatment period

Locations

Country	Name	City	State
Austria	1160.19.43004 Krankenhaus der Barmherzigen Schwestern Linz	Linz
Austria	1160.19.43002 Orthopädisches Spital Speising	Wien
Austria	1160.19.43001 A.ö. Krankenhaus d. Statutarstadt Wiener Neustadt	Wr. Neustadt
Belgium	1160.19.32002 V.U.B. Jette	Brussel
Belgium	1160.19.32004 UZ Gent	Gent
Belgium	1160.19.32005 Virga Jesseziekenhuis	Gent
Belgium	1160.19.32006 Boehringer Ingelheim Investigational Site	Huy
Belgium	1160.19.32007 C.H.U. de Tivoli	La Louvière
Czech Republic	1160.19.42004 University Hospital Brno	Brno-Bohunice
Czech Republic	1160.19.42001 Hospital Kladno	Kladno
Czech Republic	1160.19.42006 Hospital Mlada Boleslav	Mlada Boleslav
Czech Republic	1160.19.42003 University Hospital Ostrava	Ostrava
Czech Republic	1160.19.42005 University Hospital Plzen	Plzen
Czech Republic	1160.19.42009 University Hospital Na Bulovce	Prague 8
Denmark	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
Finland	1160.19.35802 Keski-Suomen keskussairaala	Jyväskylä
Finland	1160.19.35801 Oulun yliopistollinen sairaala, Leikkaus- ja tehohoidon yks.	Oulu
France	1160.19.33004 Div	Illkirch cedex
France	1160.19.33007 Clinique du Mail	La Rochelle
France	1160.19.33009 Hôpital Edouard Herriot	Lyon cedex 03
France	1160.19.33006 Clinique Mutualiste	Saint-Etienne cedex 2
France	1160.19.33008 Clinique de l'Atlantique	St Herblain cedex
Hungary	1160.19.36003 Sándor Péterfy Hospital	Budapest
Hungary	1160.19.36001 Kálmán Pándy County Hospital	Gyula
Hungary	1160.19.36004 Bács-Kiskun County Hospital	Kecskemét
Hungary	1160.19.36002 Albert Szent-Györgyi Medical and Pharmacological Center	Szeged
Hungary	1160.19.36005 Szent György Hospital	Székesfehérvár
Italy	1160.19.39003 U. O. Ortopedia e Traumatologia	Bergamo
Italy	1160.19.39005 Modulo Coordinazione Dipartimentale di Ricerca e Anestesia	Bologna
Italy	1160.19.39002 Fondazione Centro S. Raffaele	Milano
Italy	1160.19.39001 IRCCS Policlinico San Matteo	Pavia
Italy	1160.19.39004 Ospedale di Circolo di Varese	Varese
Netherlands	1160.19.31001 Boehringer Ingelheim Investigational Site	Amsterdam
Netherlands	1160.19.31003 Boehringer Ingelheim Investigational Site	Hilversum
Netherlands	1160.19.31005 Hengstdal 3	Nijmegen
Netherlands	1160.19.31006 Boehringer Ingelheim Investigational Site	Sittard
Netherlands	1160.19.31004 Boehringer Ingelheim Investigational Site	Zwolle
Norway	1160.19.47003 Helse Sunnmøre HF, Ålesund sykehus	Ålesund
Norway	1160.19.47004 Martina Hansens Hospital	Bærum Postterminal
Norway	1160.19.47008 Martina Hansens Hospital	Bærum Postterminal
Norway	1160.19.47001 Nordlandssykehuset HF, Bodø	Bodø
Norway	1160.19.47007 Sykehuset Innlandet HF, Avd. Elverum	Elverum
Norway	1160.19.47005 Haugesund sjukehus HF	Haugesund
Norway	1160.19.47002 Sykehuset Telemark HF, Avd. Skien	Skien
South Africa	1160.19.27001 Dept. of Haematology	Johannesburg
South Africa	1160.19.27002 Suite 203	Johannesburg
Sweden	1160.19.46002 Kirurgavdelningen	Falköping
Sweden	1160.19.46001	Göteborg
Sweden	1160.19.46004 Ortopediska kliniken, Länssjukhuset, Halmstad	Halmstad
Sweden	1160.19.46003 Ortopediska kliniken, Länssjukhuset i Kalmar	Kalmar
Sweden	1160.19.46007 Kungälvs sjukhus	Kungälvs
Sweden	1160.19.46005 Kirurg Ortopediska kliniken, Sjukhuset i Lidköping	Lidköping
Sweden	1160.19.46008 Ortopediska Institutionen	Linköping
Sweden	1160.19.46009 Sahlgrenska Universitetssjukhuset, Mölndal	Mölndal
Sweden	1160.19.46006 Boehringer Ingelheim Investigational Site	Varberg

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Belgium,  Czech Republic,  Denmark,  Finland,  France,  Hungary,  Italy,  Netherlands,  Norway,  South Africa,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Venous Thromboembolic (VTE) Events	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	Treatment period (up to day 8+/-2 days visit)	No
Primary	Number of Participants With Major Bleeding Events (MBE)		From approximately 14 days prior to surgery to 4-6 weeks post surgery	Yes
Secondary	Number of Participants With VTE Events and All Cause Mortality	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.	Treatment period (up to day 8+/-2 days visit)	No
Secondary	Number of Participants With Proximal DVT, PE (Pulmonary Embolism) and VTE Related Mortality	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	Treatment period (up to day 10)	No
Secondary	Number of Participants With Proximal DVT	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	Treatment period (up to day 8+/-2 days visit)	No
Secondary	Volume of Blood Loss	Volume of blood loss was to be analysed using an analysis of variance (ANOVA), which included treatment and centre.	Day 1 (Day of surgery)	No
Secondary	Rate of Transfusions Due to Bleedings	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.	Day 1 (Day of surgery)	No
Secondary	Number of Participants With Clinically Significant, Minor or Any Bleeding Events	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.	Treatment period (up to day 8+/-2 days visit)	No
Secondary	Laboratory Analyses	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 men	Screening to end of treatment	No
Secondary	Plasma Concentration (Cmax) of Dabigatran	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 state	Day 1 to end of treatment	No
Secondary	Area Under the Plasma Concentration-time Curve During a Dosing Interval	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.	up to day 8+/-2 days visit	No

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