Clinical trial NCT00398905: Dose-Ranging Study of BAY 59-7939 on the Prevention of VTE in Patients Undergoing Elective Total Hip Replacement
Official title: Controlled, Double-Blind, Randomised, Dose-Ranging Study on the Prevention of VTE in Patients Undergoing Elective Total Hip Replacement- ODIXa-HIP2 Study BAY 59-7939
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Thromboembolism
Keywords: Prevention of venous thromboembolism
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2006-11-14
Enrollment: 726
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Patients undergoing surgery, especially hip and knee surgery, are at high risk for VTE. The administration of drugs for thromboprophylaxis, such as heparins, significantly lowers that risk, but heparins have to be applied by injections below the skin. The purpose of this study was to compare the safety and efficacy of BAY 59-7939 with the safety and efficacy of the licensed drug enoxaparin and to find the optimal dose of BAY 59-7939 for the anticipated phase III trials. Enoxaparin, a so-called low molecular weight heparin, is approved and widely used in the area of thromboprophylaxis and was given once daily subcutaneously. In this study 5 different doses of the investigational drug BAY 59-7939 were tested in comparison to Enoxaparin. The following doses of BAY 59-7939 were tested: 2.5 mg twice daily (5 mg total daily dose); 5 mg twice daily (10 mg total daily dose), 10 mg twice daily (20 mg total daily dose), 20 mg twice daily (40 mg total daily dose) and 30 mg twice daily ( 60 mg total daily dose). This study ran for approximately 7 months in a number of countries. In total, 726 patients were enrolled in this study.


Eligibility criteria: Inclusion Criteria:

* Male patients aged 18 years or above and postmenopausal female patients
* Patients scheduled for elective primary total hip replacement (cemented or non-cemented prosthesis
* Patients written informed consent for participation after receiving detailed written and oral previous information to any study specific procedures

Exclusion Criteria:

* Any VTE prior to randomization
* Myocardial infarction (MI) or TIA or ischaemic stroke within the last 6 months prior to randomisation
* History of heparin-induced thrombocytopenia, allergy to heparins
* Intracerebral or intraocular bleeding within the last 6 months prior to randomisation
* History of gastrointestinal disease with gastrointestinal bleeding within the last 6 months prior to the study
* History or presence of gastrointestinal disease which could result in an impaired absorption of the study drug (e.g. severe active inflammatory bowel disease, short gut syndrome)
* Amputation of one leg
* Heart insufficiency NYHA III-IV
* Congenital or acquired haemorrhagic diathesis (PT INR/aPTT not within normal limits) including patients with acquired or congenital thrombopathy
* Thrombocytopenia (platelets \< 100.000/µl)
* Macroscopic haematuria.
* Allergy to contrast media.
* Severe hypertension (SBP \> 200mmHg, DBP \> 100 mmHg)
* Impaired liver function (transaminases \> 2 x ULN)
* Impaired renal function (serum creatinine \> 1.5 x ULN or creatinine clearance \< 30 ml/min)
* Active malignant disease
* Presence of active peptic ulcer or gastrointestinal disease with increased risk of gastrointestinal bleeding
* Body weight \< 45 kg
* Drug- or alcohol abuse
* Patients who cannot stop therapy ( in the opinion of the investigator/ physician) with anticoagulants (e.g. phenprocoumon, warfarin-sodium, heparins and factor Xa inhibitors other than study medication) and fibrinolytic therapy should be excluded from the study
* Therapy with acetylic salicylic acid or other thrombocyte aggregation inhibitors (e.g. clopidogrel, dipyridamole and ticlopidine) should be stopped one week before enrolment. Patients not able to stop ASA therapy will be excluded
* All other drugs influencing coagulation, (exception: NSAIDs with half life \< 17 hrs will be allowed)
* Systemic and topical treatment with azole compounds (e.g. ketoconazole, fluconazole, itraconazole) and other strong CYP3A4 inhibitors e.g. HIV-protease inhibitors. Azole compounds and other strong CYP3A4 inhibitors
* Therapy with another investigational product within 30 days prior start of study
* Planned intermittent pneumatic compression during active treatment period
* Planned epidural anaesthesia with indwelling epidural catheter (spinal or epidural anaesthesia without indwelling catheter are allowed)
* Concomitant participation in another trial or study

Primary outcomes:
measure: Composite Endpoint: Any Deep Vein Thrombosis (DVT) (proximal and/or distal) and Non fatal Pulmonary Embolism (PE) and Death from all causes
timeFrame: 5-9 days after surgery
Secondary outcomes:
measure: Incidence of DVTs (total, proximal, distal)
timeFrame: 5-9 days after surgery
measure: Incidence of symptomatic Venous Thrombo Embolisms (VTEs)
timeFrame: 5-9 days after surgery
measure: Incidence of symptomatic VTEs (total, PE, DVT) within 30 days after stop of treatment with the study drug
timeFrame: 40 days
measure: Healthcare Resource Utilisation Questionnaire
timeFrame: 9 days and 40 days after surgery
Other outcomes:
Locations:
city: Wiener Neustadt
country: Austria
state: Niederösterreich
city: Linz
country: Austria
state: Oberösterreich
city: Wien
country: Austria
city: Baudour
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Genk
country: Belgium
city: HUY
country: Belgium
city: Sint-truiden
country: Belgium
city: Hellerup
country: Denmark
city: Herlev
country: Denmark
city: Hørsholm
country: Denmark
city: Silkeborg
country: Denmark
city: Amiens
country: France
city: Lille Cedex
country: France
city: Poitiers
country: France
city: Rheinfelden
country: Germany
state: Baden-Württemberg
city: Ulm
country: Germany
state: Baden-Württemberg
city: Fürth
country: Germany
state: Bayern
city: Garmisch-Partenkirchen
country: Germany
state: Bayern
city: Sommerfeld
country: Germany
state: Brandenburg
city: Frankfurt
country: Germany
state: Hessen
city: Frankfurt
country: Germany
state: Hessen
city: Marburg
country: Germany
state: Hessen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Dresden
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Haifa
country: Israel
city: Tel Aviv
country: Israel
city: Tel Hashomer
country: Israel
city: Zerifin
country: Israel
city: Rozzano
country: Italy
state: Milano
city: Gubbio
country: Italy
state: Perugia
city: Milano
country: Italy
city: Pavia
country: Italy
city: Perugia
country: Italy
city: Reggio Emilia
country: Italy
city: Varese
country: Italy
city: Hilversum
country: Netherlands
city: Nijmegen
country: Netherlands
city: Sittard
country: Netherlands
city: Bodø
country: Norway
city: Drammen
country: Norway
city: Notodden
country: Norway
city: Oslo
country: Norway
city: Rjukan
country: Norway
city: Bialystok
country: Poland
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Badalona
country: Spain
state: Barcelona
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Valencia
country: Spain
city: Göteborg
country: Sweden
city: Halmstad
country: Sweden
city: Jönköping
country: Sweden
city: Kungälv
country: Sweden
city: London
country: United Kingdom
state: Greater London
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: