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Completed

NCT Number: NCT01225822

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.

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Key information

Conditions

Venous Thromboembolism Cardiovascular Diseases Embolism and Thrombosis Thromboembolism Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

1160.19.43004 Krankenhaus der Barmherzigen Schwestern Linz, Linz, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients scheduled to undergo a primary elective total hip or knee replacement.
  • Male of female being 18 years or older.
  • Patients weighing at least 40 kg.
  • Written informed consent for study participation.

Exclusion criteria

  • Bleeding diathesis, constitutional or acquired coagulation disorders.
  • Major surgery or trauma(e.g., hip fracture) within the last 3 months.
  • Cardiovascular disease
  • Any history of haemorrhagic stroke, intracranial or intraocular bleeding or cerebral ischaemic attacks lasting more than 24 hours and / or with cardiovascular pathological findings.
  • Deep vein thrombosis(DVT), gastrointestinal or pulmonary bleeding, gastric or duodenal ulcer within the last year.
  • History of or acute intracranial disease
  • Liver disease
  • Renal disease
  • Use of long-term anticoagulants or antiplatelet drugs within 7 days prior to hip/knee replacement operation.
  • 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
  • Known allergy to contrast media
  • Thrombocytopenia
  • Allergy against heparin.
  • Active malignant disease or current cytostatic treatment.
  • Treatment with an investigational drug in the past month.
  • Leg amputee
  • Known alcohol or drug abuse

Treatment and study plan

Enoxaparin

Drug

Enoxaparin 40 mg s.c once a day for 5-10 days of treatment period

BIBR 1048

Drug

50 mg b.i.d BIBR 1048 capsule twice a day for 5-10 days of treatment period

Primary outcomes

  1. Number of Participants With Venous Thromboembolic (VTE) Events

    Time frame: 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

  2. Number of Participants With Major Bleeding Events (MBE)

    Time frame: From approximately 14 days prior to surgery to 4-6 weeks post surgery

Secondary outcomes

  1. Number of Participants With VTE Events and All Cause Mortality

    Time frame: 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.

  2. Number of Participants With Proximal DVT, PE (Pulmonary Embolism) and VTE Related Mortality

    Time frame: 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

  3. Number of Participants With Proximal DVT

    Time frame: 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

  4. Volume of Blood Loss

    Time frame: Day 1 (Day of surgery)

    Volume of blood loss was to be analysed using an analysis of variance (ANOVA), which included treatment and centre.

  5. Rate of Transfusions Due to Bleedings

    Time frame: 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.

  6. Number of Participants With Clinically Significant, Minor or Any Bleeding Events

    Time frame: 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.

  7. Laboratory Analyses

    Time frame: 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 men

  8. Plasma Concentration (Cmax) of Dabigatran

    Time frame: 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 state

  9. Area Under the Plasma Concentration-time Curve During a Dosing Interval

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Important dates

Study start
2002
Primary completion
2003
First posted
Oct 21, 2010
Registry last updated
May 19, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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