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

NCT02170701 | Completed Phase 2

• 1 other identifier: 1160.11
• Study Type: interventional
• Target: 289
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Venous Thromboembolism

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (1)

• Venous thromboembolism diagnosed during the follow-up period

  Up to 6 weeks after surgery (day 42)

Study Arms (1)

BIBR 1048

EXPERIMENTAL

Ascending doses (in mg) given twice daily

Drug: BIBR 1048

Interventions

BIBR 1048 DRUG

Ascending doses (in mg) given twice daily

BIBR 1048

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

Dabigatran

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 23, 2014
• Study Start: October 1, 2000
• Primary Completion: June 1, 2001
• Last Updated: August 31, 2018

Record last verified: 2018-08