Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

October 20, 2010
May 8, 2014
November 2002
August 2003   (final data collection date for primary outcome measure)
  • 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 ]
  • The primary efficacy endpoint of this trial is the incidence of Venous thromboembolism(VTE) during the treatment period. [ Time Frame: 5-10 days ] [ Designated as safety issue: No ]
  • The primary safety endpoint is the rate of major bleeding events(MBE) during the treatment period. [ Time Frame: 5-10 days ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01225822 on ClinicalTrials.gov Archive Site
  • 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.
  • The secondary endpoint includes incidence of any deep vein thrombosis(DVT), Pulmonary embolism(PE) and all cause mortality, incidence of clinically significant, minor, any bleeding events during the treatment period. [ Time Frame: 5-10 days ] [ Designated as safety issue: Yes ]
  • The secondary efficacy endpoint of this trial is diagnosis of Venous Thromboembolism during follow-up period. [ Time Frame: 4-6 weeks after surgery ] [ Designated as safety issue: No ]
  • The incidence of proximal deep vein thrombosis(DVT) during the treatment period will also be analysed as a secondary efficacy endpoint. [ Time Frame: 5-10 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
BIBR 1048 Dose Range Finding Study in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip or Knee Replacement Surgery
BIBR 1048 Dose Range Finding Study in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip or Knee Replacement Surgery

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Venous Thromboembolism
  • Drug: Enoxaparin
    Enoxaparin 40 mg s.c once a day for 5-10 days of treatment period
  • Drug: BIBR 1048
    50 mg b.i.d BIBR 1048 capsule twice a day for 5-10 days of treatment period
  • Drug: BIBR 1048
    150 mg b.i.d BIBR 1048 capsule twice a day for 5-10 treatment period
  • Drug: BIBR 1048
    225 mg b.i.d BIBR 1048 capsule twice a day for 5-10 treatment period
  • Drug: BIBR 1048
    300 mg q.d BIBR 1048 capsule for 5-10 treatment period
  • 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
    Intervention: Drug: BIBR 1048
  • 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
    Intervention: Drug: BIBR 1048
  • 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
    Intervention: Drug: BIBR 1048
  • 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
    Intervention: Drug: BIBR 1048
  • 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
    Intervention: Drug: Enoxaparin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1973
Not Provided
August 2003   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Austria,   Belgium,   Czech Republic,   Denmark,   Finland,   France,   Hungary,   Italy,   Netherlands,   Norway,   South Africa,   Sweden
 
NCT01225822
1160.19
Not Provided
Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP