Multicenter, Open-label, Ascending Dose Study of BIBR 1048 in the Prevention of Venous Thromboembolism in Patients Undergoing Primary Elective Total Hip Replacement Surgery. Bistro I
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 289
- Primary Endpoint
- Changes from baseline in ecarin clotting time (ECT)
Study Overview
Brief Summary
- To determine the therapeutic window of BIBR 1048 in order to select doses for further studies in the development plan.
- Twice daily regimen will be tested for most dose levels and once daily administration will also be evaluated when appropriate.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients scheduled to undergo a primary elective total hip 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 three months. Patients with previous hip fractures associated with plate revisions at any time will be excluded
- •Cardiovascular disease including uncontrolled hypertension at time of enrolment or history of myocardial infarction within the last 6 months
- •Any history of haemorrhagic stroke, intracranial or intraocular bleeding or cerebral ischaemic attacks
- •Known history of deep venous thrombosis (DVT)
- •Gastrointestinal or pulmonary bleeding within the last year
- •Known liver disease Aspartate transaminase (AST) or Alanine transaminase (ALT) > 3 x ULN)
- •Known renal disease (serum creatinine > 1.5 x ULN)
- •Use of long- term anticoagulants, antiplatelet drugs, or fibrinolytics within 7 days prior to hip replacement operation (also contraindicated during the period of prophylaxis)
- •Women of childbearing potential
- •Known allergy to radiopaque contrast media
- •Known thrombocytopenia (prior platelet count below 100,000 cells/microliter)
- •Active malignant disease
- •Current H2 blocker or proton pump inhibitor treatment
- •Current cytostatic treatment
- •Treatment with an investigational drug in the past month
- •Leg amputee
- •Known alcohol or drug abuse
Arms & Interventions
BIBR 1048
Ascending doses (in mg) given twice daily
Intervention: BIBR 1048 (Drug)
Outcomes
Primary Outcomes
Changes from baseline in ecarin clotting time (ECT)
Time Frame: From baseline (day -14 to day -1 before treatment) until last day of treatment (up to day 10)
Changes from baseline in thrombin time (TT)
Time Frame: From baseline (day -14 to day -1 before treatment) until last day of treatment (up to day 10)
Rate of venous thrombolic events
Time Frame: Up to day 10 after hip surgery
Changes from baseline in activated partial thromboplastin time (aPTT)
Time Frame: From baseline (day -14 to day -1 before treatment) until last day of treatment (up to day 10)
Cpre,ss (predose plasma concentrations at steady state)
Time Frame: baseline and predose from day 1 to last treatment day
Rate of major bleeding events during treatment phase
Time Frame: Start of treatment (day 0) until end of treatment (up to day 10)
Cmax,ss (maximum plasma concentration at steady state (day 4))
Time Frame: Day 4 before and 0.5, 1, 2, 4 , 8, 12 , 14 h after treatment
Tmax,ss (time to reach Cmax,ss)
Time Frame: baseline, day 0 before and 4 hours after, day 1 to 4 before and 2 h after treatment, day 5 to last treatment day before treatment
CLtot/f (total clearance of drug from plasma after oral administration)
Time Frame: baseline, day 0 before and 4 hours after, day 1 to 4 before and 2 h after treatment, day 5 to last treatment day before treatment
AUCss (area under the plasma concentration curve of one dosing interval at steady state)
Time Frame: baseline, day 0 before and 4 hours after, day 1 to 4 before and 2 h after treatment, day 5 to last treatment day before treatment
PTF (percent peak trough fluctuation for the last dosing interval)
Time Frame: baseline, day 0 before and 4 hours after, day 1 to 4 before and 2 h after treatment, day 5 to last treatment day before treatment
Secondary Outcomes
- Venous thromboembolism diagnosed during the follow-up period(Up to 6 weeks after surgery (day 42))