Dose-ranging Study of Once-daily Regimen of BAY 59-7939 in the Prevention of VTE in Patients Undergoing Elective Total Hip Replacement (ODIXaHIP-OD)

Controlled, Double-Blind, Randomized, Dose-ranging Study of Once-daily Regimen of BAY59-7939 in the Prevention of VTE in Patients Undergoing Elective Total Hip Replacement- ODIXaHIP-OD

The purpose of this study is to assess different doses of a new drug (BAY 59-7939), taken as a tablet, are safe and can help prevent blood clots forming after a hip replacement operation. Patients undergoing hip replacement surgery are at risk of developing blood clots. To reduce this risk treatment to prevent clots forming is routinely given. The current treatments can include injections under the skin or other treatments that need frequent blood tests to monitor levels of drug in the body. Therefore there is a need for new drugs, which are easier to give and need less monitoring.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Enoxaparin

• Study Type: Interventional
• Enrollment (Actual): 877
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1220
  • Niederösterreich
    • Wiener Neustadt, Niederösterreich, Austria, 2700
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4010
    • Linz, Oberösterreich, Austria, 4020
• Belgium
  • Antwerpen, Belgium, 2020
  • Bonheiden, Belgium, 2820
  • Genk, Belgium, 3600
  • Hasselt, Belgium, 3500
• Denmark
  • Hellerup, Denmark, 2900
  • Herlev, Denmark, 2730
  • Hørsholm, Denmark, DK-2970
  • Silkeborg, Denmark, 8600
• France
  • Paris Cedex 14, France, 75877
  • Paris Cedex 19, France, 75019
  • Poitiers, France, 86000
  • Saint Herblain, France, 44819
• Germany
  • Baden-Württemberg
    • Rheinfelden, Baden-Württemberg, Germany, 79618
  • Bayern
    • Fürth, Bayern, Germany, 90766
    • Garmisch-Partenkirchen, Bayern, Germany, 82467
  • Brandenburg
    • Sommerfeld, Brandenburg, Germany, 16766
  • Hessen
    • Frankfurt, Hessen, Germany, 60528
    • Frankfurt, Hessen, Germany, 65929
    • Marburg, Hessen, Germany, 35043
    • Melsungen, Hessen, Germany, 34212
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
• Israel
  • Haifa, Israel, 31096
  • Holon, Israel, 58100
  • Kfar Saba, Israel, 44281
  • Petach Tikva, Israel, 49100
  • Tel Aviv, Israel, 64239
  • Zerifin, Israel, 70300
  • Isarel
    • Petach Tikva, Isarel, Israel, 49372
• Italy
  • Bologna, Italy, 40136
  • Milano, Italy, 20122
  • Milano, Italy, 20132
  • Milano
    • Monza, Milano, Italy, 20052
    • Rozzano, Milano, Italy, 20089
  • Perugia
    • Gubbio, Perugia, Italy, 06024
• Netherlands
  • Hilversum, Netherlands, 1213 XZ
  • Hoofddorp, Netherlands, 2134 TM
  • Nijmegen, Netherlands, 6522 JV
• Norway
  • Notodden, Norway, NO-3675
  • Oslo, Norway, 0440
  • Rjukan, Norway, NO-3660
• Poland
  • Bialystok, Poland, 15-276
  • Gdansk, Poland, 80-742
  • Krakow, Poland, 31-826
  • Lublin, Poland, 20-090
  • Lublin, Poland, 20-718
  • Warszawa, Poland, 00-909
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08035
  • Madrid, Spain, 28040
  • Valencia, Spain, 46010
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
• Sweden
  • Göteborg, Sweden, 416 85
  • Halmstad, Sweden, 301 85
  • Jönköping, Sweden, 551 85
  • Kungälv, Sweden, 442 83
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
    • London, Greater London, United Kingdom, W6 0TN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

• Related to medical history:

  • 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 legRelated to current symptoms or findings:

  • Heart insufficiency NYHA class 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 > 200 mmHg, 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- Related to current treatment- 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) should be excluded from the study
  • Fibrinolytic therapy- Therapy with acetylic salicylic acid or other platelet 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 not allowed during the study treatment period- Systemic and topical treatment with azole compounds (e.g. ketoconazole, fluconazole, itraconazole) and other strong CYP3A4-inhibitors eg HIV-protease inhibitors. Azole compounds and other strong CYP3A4-inhibitors eg HIV-protease should be stopped at least four days before enrolment
• Therapy with another investigational product within 30 days prior start of study
• Miscellaneous
• Planned intermittent pneumatic compression during active treatment period
• Planned epidural anaesthesia with indwelling epidural catheter (spinal or epidural anaesthesia without indwelling catheter are allowed)
• If traumatic or repeated epidural and spinal puncture occur the patient should be excluded from study
• Concomitant participation in another trial or study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 5 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 10 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 20 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 30 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 40 mg once daily plus placebo enoxaparin syringe
Experimental: Arm 2	Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 5 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 10 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 20 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 30 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 40 mg once daily plus placebo enoxaparin syringe
Experimental: Arm 3	Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 5 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 10 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 20 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 30 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 40 mg once daily plus placebo enoxaparin syringe
Experimental: Arm 4	Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 5 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 10 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 20 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 30 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 40 mg once daily plus placebo enoxaparin syringe
Experimental: Arm 5	Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 5 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 10 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 20 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 30 mg once daily plus placebo enoxaparin syringe; Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 40 mg once daily plus placebo enoxaparin syringe
Active Comparator: Arm 6	Drug: Enoxaparin; Enoxaparin 40 mg once daily plus Rivaroxaban placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite Endpoint of Deep Vein Thrombosis (DVT), non-fatal Pulmonary Embolism (PE) and Death from all causes	6-10 days after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of symptomatic VTEs (total, PE, DVT) within 30 days after stop of treatment with the study drug	40 days
Incidence of DVTs (total, proximal, distal)	6-10 days after surgery
Incidence of symptomatic Venous Thrombo Embolisms (VTEs)	6-10 days after surgery
Incidence of major VTE (ie, Proximal DVT, PE or VTE-related death)	6-10 days after surgery
The composite endpoint that results from the primary endpoint by substituting VTE related death for all death	40 days

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here and search for information of Bayer products for Europe

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): July 1, 2005
• Study Completion (Actual): July 1, 2005

Study Registration Dates

• First Submitted: November 6, 2006
• First Submitted That Met QC Criteria: November 6, 2006
• First Posted (Estimate): November 7, 2006

Study Record Updates

• Last Update Posted (Estimate): October 28, 2014
• Last Update Submitted That Met QC Criteria: October 27, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Prevention of venous thromboembolism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Enoxaparin
• Other Study ID Numbers: 11527; EudraCT No: 2004-001341-14