ODiXahip - a Phase IIa Dose Escalating Proof of Principle Trial (ODiXaHip)

Oral Direct Factor Xa Inhibitor BAY 59-7939 in the Prevention of VTE in Patients Undergoing Total Hip Replacement. ODiXahip - a Phase IIa Dose Escalating Proof of Principle Trial

Patients undergoing surgery, especially hip and knee surgery, are at high risk for VTE (up to 60 % without prophylaxis). The administration of drugs for thromboprophylaxis, such as heparins, significantly lowers that risk, but heparins have to be applied below the skin (subcutaneously). Additionally, there is a chance of developing a heparin-induced thrombocytopenia (decrease in platelets). Therefore, there is still a need for new agents which are safer and more efficient and which are easier to apply.The purpose of this study is to compare the safety and efficacy of BAY 59-7939 with the safety and efficacy of the licensed drug Enoxaparin. Enoxaparin, a so-called low molecular heparin, is approved and widely used in the area of thromboprophylaxis and will be given once daily subcutaneously.Another important purpose of the study is to find the optimal dose of BAY 59-7939 for thromboprophylaxis after hip replacement surgery. Therefore, there are several dose steps planned.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 641
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1220
  • Niederösterreich
    • Wiener Neustadt, Niederösterreich, Austria, 2700
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4010
• Belgium
  • Baudour, Belgium, 7331
  • Bruxelles, Belgium, 1090
  • Gent, Belgium, 9000
  • HUY, Belgium, 4500
• Denmark
  • Hellerup, Denmark, 2900
  • Herlev, Denmark, 2730
  • Hørsholm, Denmark, DK-2970
  • Silkeborg, Denmark, 8600
• France
  • Amiens, France, 80030
  • Lille Cedex, France, 59037
  • Nancy, France, 54037
• Germany
  • Berlin, Germany, 14165
  • Baden-Württemberg
    • Rheinfelden, Baden-Württemberg, Germany, 79618
  • Bayern
    • Fürth, Bayern, Germany, 90766
    • Garmisch-Partenkirchen, Bayern, Germany, 82467
  • Hessen
    • Frankfurt, Hessen, Germany, 60528
    • Frankfurt, Hessen, Germany, 65929
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
• Israel
  • Haifa, Israel, 31096
  • Tel Aviv, Israel, 64239
  • Tel Hashomer, Israel, 52621
  • Zerifin, Israel, 70300
• Netherlands
  • Amersfoort, Netherlands, 3818 ES
  • Zwolle, Netherlands, 8025 AB
• 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
  • Lodz, Poland, 91-425
  • Lublin, Poland, 20-090
  • Lublin, Poland, 20-718
  • Warszawa, Poland, 00-909
• Sweden
  • Göteborg, Sweden, 416 85
  • Jönköping, Sweden, 551 85
  • Kungälv, Sweden, 442 83
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS

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:

• 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:

• DVT or PE within the previous 6 months prior to study entry.
• Myocardial infarction (MI) or cerebrovascular attack (CVA), TIA or ischaemic stroke within the last 6 months prior to study entry.
• History of heparin-induced thrombocytopenia, allergy to heparins.
• Intracerebral or intraocular bleeding within the last 6 months prior to study entry.
• 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
• Amputation of one leg.Related to current symptoms or findings
• Heart insufficiency NYHA III-IV.
• Congenital or acquired haemorrhagic diathesis (PT INR/aPTT not within normal limits).
• Thrombocytopenia (platelets < 50.000/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).
• 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

  • Therapy with oral anticoagulants (e.g. phenprocoumon, warfarin-sodium).
  • Therapy with acetylic salicylic acid or other thrombocyte aggregation inhibitors (e.g. clopidogrel, dipyridamole and ticlopidine) should be stopped one week before enrolment
  • Treatment with heparins or Factor Xa Inhibitors other than study medication.
  • All other drugs influencing coagulation, (exception: NSAIDs with half life < 17 hrs will be allowed).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 2	Drug: Enoxaparin; 40 mg bid
Experimental: Arm 1	Drug: Rivaroxaban (BAY59-7939); 2,5 mg bid,5 mg bid,10mg bid, 20 mg bid, 20 mg tid, 30 mg bid, dose escalation trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary efficacy endpoint is a composite endpoint of: - Any DVT (proximal and/or distal) and - Non fatal PE and - Death from all causes. The primary endpoint will be evaluated 5 - 9 days after surgery.	Assymptomatic DVT will be measured 5-9 days after surgery Symptomatc DVT , non-fatal PE and Death from all causes will be measured 41 days after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of DVTs (total, proximal, distal)	will be evaluated 5 - 9 days after surgery.
Incidence of symptomatic VTEs	41 days after surgery
The composite endpoint that results from the primary endpoint by using alternative definition of deaths (i.e. VTE related death)	41 days after surgery
Incidence of symptomatic VTEs (total, PE, DVT) within 30 days after stop of treatment with the study drug.	41 days after surgery

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Primary Completion (Actual): November 1, 2003
• Study Completion (Actual): November 1, 2003

Study Registration Dates

• First Submitted: February 9, 2009
• First Submitted That Met QC Criteria: February 9, 2009
• First Posted (Estimate): February 10, 2009

Study Record Updates

• Last Update Posted (Estimate): December 17, 2014
• Last Update Submitted That Met QC Criteria: December 15, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Prevention of Thromboembolism after total hip replacement
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; 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: 10942