BIBR 1048 in the Prevention of Venous Thromboembolism in Patients Undergoing Primary Elective Total Hip Replacement Surgery

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

• 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 Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: BIBR 1048

• Study Type: Interventional
• Enrollment (Actual): 289
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BIBR 1048; Ascending doses (in mg) given twice daily	Drug: BIBR 1048; Ascending doses (in mg) given twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of venous thrombolic events	Up to day 10 after hip surgery
Changes from baseline in activated partial thromboplastin time (aPTT)	From baseline (day -14 to day -1 before treatment) until last day of treatment (up to day 10)
Changes from baseline in ecarin clotting time (ECT)	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)	From baseline (day -14 to day -1 before treatment) until last day of treatment (up to day 10)
Rate of major bleeding events during treatment phase	Start of treatment (day 0) until end of treatment (up to day 10)
Cpre,ss (predose plasma concentrations at steady state)	baseline and predose from day 1 to last treatment day
Cmax,ss (maximum plasma concentration at steady state (day 4))	Day 4
Tmax,ss (time to reach Cmax,ss)	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)	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)	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)	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
Cmax,ss (maximum plasma concentration at steady state (day 4))	Day 4 before and 0.5, 1, 2, 4 , 8, 12 , 14 h after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Venous thromboembolism diagnosed during the follow-up period	Up to 6 weeks after surgery (day 42)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (ACTUAL): June 1, 2001

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (ESTIMATE): June 23, 2014

Study Record Updates

• Last Update Posted (ACTUAL): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 29, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 1160.11