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

Venous Thromboembolism Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02170701
• Other study ID #: 1160.11
• Status: Completed
• Phase: Phase 2
• Start date: October 2000

Study information

• Verified date: August 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 289
• Est. primary completion date: June 2001
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• BIBR 1048
Ascending doses (in mg) given twice daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of venous thrombolic events		Up to day 10 after hip surgery
Primary	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)
Primary	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)
Primary	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)
Primary	Rate of major bleeding events during treatment phase		Start of treatment (day 0) until end of treatment (up to day 10)
Primary	Cpre,ss (predose plasma concentrations at steady state)		baseline and predose from day 1 to last treatment day
Primary	Cmax,ss (maximum plasma concentration at steady state (day 4))		Day 4
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Venous thromboembolism diagnosed during the follow-up period		Up to 6 weeks after surgery (day 42)