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Efficacy and Safety of TAK-442 in Subjects Undergoing Total Knee Replacement

Phase 2
Completed
Conditions
Venous Thromboembolism
Interventions
Registration Number
NCT00641732
Lead Sponsor
Takeda
Brief Summary

The purpose of this study is to determine if TAK-442, once daily (QD) or twice daily (BID), is as safe and effective as enoxaparin in preventing the development of blood clots after knee replacement surgery.

Detailed Description

Takeda Global Research \& Development Center, Inc. is developing the compound TAK-442 as a candidate for the secondary prevention of atherothrombotic events in patients with acute coronary syndromes. TAK-442 is an oral inhibitor of activated factor X within the blood coagulation cascade.

Due to its critical role in propagating the coagulation cascade, activated factor X is now considered to be a therapeutic aim in the development of anticoagulant drugs. Therefore activated factor X inhibitors, are among the agents under investigation as treatments for the spectrum of thromboembolic diseases involving either the arterial or the venous system.

Short term anticoagulation is often used for the prevention of venous thromboembolism. Patients undergoing major orthopedic surgery are at particularly high risk of venous thromboembolism after surgery. Consequently, such patients are routinely given anticoagulant medication after surgery. Although parenteral (injectable) drugs, such as enoxaparin or fondaparinux, can be used for this indication, the need for subcutaneous injection is problematic once patients are discharged from hospital. With the push for shorter hospital stays, this issue is of increasing concern. Therefore, there is a need for new oral anticoagulants. Although warfarin can be used for out of hospital prophylaxis, the need for coagulation monitoring and dose adjustments complicates its use. The new oral anticoagulants have the potential to overcome this problem because they can be given in fixed doses without the need for coagulation monitoring.

The purpose of the current study is to evaluate the antithrombotic effect of TAK-442 in patients undergoing elective total knee replacement surgery. This study will be the first TAK-442 trial in patients.

Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be approximately 2.25 months. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations, electrocardiograms and bilateral venogram. Outside of the study center, participants randomized to enoxaparin will be required to administer study medication subcutaneously with a syringe.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1045
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TAK-442 40 mg BIDTAK-442-
TAK-442 40 mg QDTAK-442-
TAK-442 80 mg QDTAK-442-
TAK-442 10 mg BIDTAK-442-
TAK-442 20 mg BIDTAK-442-
Enoxaparin 30 mg BIDEnoxaparin-
TAK-442 80 mg BIDTAK-442-
Primary Outcome Measures
NameTimeMethod
Incidence of Major Bleeding.Day 10.
Composite evaluation of All-Cause Mortality, Symptomatic and Asymptomatic Deep Vein Thrombosis and Symptomatic Pulmonary Embolism.Day 10.
Secondary Outcome Measures
NameTimeMethod
Evaluation of Symptomatic Venous Thromboembolism.Day 10.
Evaluation of Major Venous Thromboembolism (composite of Symptomatic or Asymptomatic Proximal Deep Vein Thrombosis, Symptomatic Objectively Confirmed Pulmonary Embolism, and Venous Thromboembolism-Related Death).Day 10.
Evaluation of Proximal Deep Vein Thrombosis.Day 10.
Evaluation of Minor Bleeding events.Day 10.
Evaluation of Distal Deep Vein Thrombosis.Day 10.
Evaluation of clinically significant Non-Major Bleeding events.Day 10.
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