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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01225822
First received: October 20, 2010
Last updated: May 8, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Venous Thromboembolism
Drug: Enoxaparin
Drug: BIBR 1048
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: BIBR 1048 Dose Range Finding Study in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip or Knee Replacement Surgery

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Number of Participants With Venous Thromboembolic (VTE) Events [ Time Frame: Treatment period (up to day 8+/-2 days visit) ] [ Designated as safety issue: No ]
    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) [ Time Frame: From approximately 14 days prior to surgery to 4-6 weeks post surgery ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of Participants With VTE Events and All Cause Mortality [ Time Frame: Treatment period (up to day 8+/-2 days visit) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Treatment period (up to day 10) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Treatment period (up to day 8+/-2 days visit) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (Day of surgery) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (Day of surgery) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Treatment period (up to day 8+/-2 days visit) ] [ Designated as safety issue: No ]

    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 [ Time Frame: Screening to end of treatment ] [ Designated as safety issue: No ]

    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


  • Plasma Concentration (Cmax) of Dabigatran [ Time Frame: Day 1 to end of treatment ] [ Designated as safety issue: No ]

    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


  • Area Under the Plasma Concentration-time Curve During a Dosing Interval [ Time Frame: up to day 8+/-2 days visit ] [ Designated as safety issue: No ]
    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.


Enrollment: 1973
Study Start Date: November 2002
Primary Completion Date: August 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBR 1048 50 mg bis in die(b.i.d)
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
Drug: BIBR 1048
50 mg b.i.d BIBR 1048 capsule twice a day for 5-10 days of treatment period
Experimental: BIBR 1048 150 mg b.i.d
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
Drug: BIBR 1048
150 mg b.i.d BIBR 1048 capsule twice a day for 5-10 treatment period
Experimental: BIBR 1048 225 mg b.i.d
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
Drug: BIBR 1048
225 mg b.i.d BIBR 1048 capsule twice a day for 5-10 treatment period
Experimental: BIBR 1048 300 mg quaque die(q.d)
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
Drug: BIBR 1048
300 mg q.d BIBR 1048 capsule for 5-10 treatment period
Active Comparator: Enoxaparin 40 mg subcutaneous(s.c)
placebo matching BIBR 1048 0 mg twice a day plus enoxaparin 40 mg s.c once a day for the treatment period
Drug: Enoxaparin
Enoxaparin 40 mg s.c once a day for 5-10 days of treatment period

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225822

  Show 59 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01225822     History of Changes
Other Study ID Numbers: 1160.19
Study First Received: October 20, 2010
Results First Received: November 18, 2010
Last Updated: May 8, 2014
Health Authority: Austria:
Belgium:
Czech Republic:
Denmark:
Finland:
France:
Hungary:
Italy: Ethics Committee
Netherlands:
Norway:
South Africa:
Sweden:

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Dabigatran
Enoxaparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014