Clinical trial NCT02170701: BIBR 1048 in the Prevention of Venous Thromboembolism in Patients Undergoing Primary Elective Total Hip Replacement Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Thromboembolism
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-23
Enrollment: 289
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Rate of venous thrombolic events
timeFrame: Up to day 10 after hip surgery
measure: Changes from baseline in activated partial thromboplastin time (aPTT)
timeFrame: From baseline (day -14 to day -1 before treatment) until last day of treatment (up to day 10)
measure: Changes from baseline in ecarin clotting time (ECT)
timeFrame: From baseline (day -14 to day -1 before treatment) until last day of treatment (up to day 10)
measure: Changes from baseline in thrombin time (TT)
timeFrame: From baseline (day -14 to day -1 before treatment) until last day of treatment (up to day 10)
measure: Rate of major bleeding events during treatment phase
timeFrame: Start of treatment (day 0) until end of treatment (up to day 10)
measure: Cpre,ss (predose plasma concentrations at steady state)
timeFrame: baseline and predose from day 1 to last treatment day
measure: Cmax,ss (maximum plasma concentration at steady state (day 4))
timeFrame: Day 4
measure: Tmax,ss (time to reach Cmax,ss)
timeFrame: 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
measure: CLtot/f (total clearance of drug from plasma after oral administration)
timeFrame: 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
measure: AUCss (area under the plasma concentration curve of one dosing interval at steady state)
timeFrame: 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
measure: PTF (percent peak trough fluctuation for the last dosing interval)
timeFrame: 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
measure: Cmax,ss (maximum plasma concentration at steady state (day 4))
timeFrame: Day 4 before and 0.5, 1, 2, 4 , 8, 12 , 14 h after treatment
Secondary outcomes:
measure: Venous thromboembolism diagnosed during the follow-up period
timeFrame: Up to 6 weeks after surgery (day 42)
Other outcomes:
Locations:
Study officials:
References: