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Venous ThromboembolismPhase 2NCT00641732

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

A Phase 2 study testing TAK-442 and Enoxaparin in people with Venous Thromboembolism, run by Takeda at 64 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Venous Thromboembolism
What is being tested?
TAK-442 and Enoxaparin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,045 participants
Where
64 sitesin 2 countries
Study dates
Oct 2007to Oct 2008
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Scheduled to undergo elective, unilateral, primary, total knee replacement.
  • Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
  • Screening laboratory tests (including clinical chemistry, hematology, and complete urinalysis) are within the reference range for the testing laboratory or are determined not to compromise subject safety by the investigator.

Who cannot join

  • Received TAK-442 in a previous clinical study or as a therapeutic agent.
  • Body weight greater than 150 kg.
  • Known bleeding diathesis (including Von Willebrand's disease or Hemophilia A or B).
  • History of intracerebral, intraocular, or gastrointestinal bleeding, or active gastric or duodenal ulceration, within the 6 months prior to Randomization.
  • Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including throughout the treatment period of the study due to an increased risk of bleeding, and should be stopped at least 5 days prior to surgery and in accordance with the product information:
  • Parenteral anticoagulants
Show all 40Show fewer
  • Unfractionated heparin
  • Low molecular weight heparin (eg, dalteparin, non-study enoxaparin)
  • Direct thrombin inhibitors (eg, bivalirudin, argatroban)
  • Factor Xa inhibitors (eg, fondaparinux)
  • Oral anticoagulants
  • Warfarin
  • Anisindione
  • Antiplatelet drugs
  • Aspirin greater than 162 mg/day
  • Clopidogrel
  • Ticlopidine
  • Cilostazol
  • Dipyridamole
  • Glycoprotein IIb/IIIa inhibitors (eg, abciximab, eptifibatide)
  • NSAIDs with a half life greater than or equal to 17 hours
  • Meloxicam
  • Fibrinolytic agents
  • tPA (alteplase, reteplase, tenecteplase)
  • History of major surgery within 3 months prior to randomization; or deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident, or transient ischemic attack within 6 months prior to randomization.
  • History of hypersensitivity or allergies to other activated factor X inhibitors or enoxaparin (or other low molecular weight heparins).
  • Condition prohibiting bilateral venography.
  • Has had multiple or traumatic epidural or spinal punctures immediately prior to randomization (defined as grossly bloody or greater than 3 attempted cannulations).
  • Requires use of an indwelling epidural catheter for post-operative analgesia.
  • Severe hypertension defined as systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 110 mmHg at Screening.
  • Moderate to severe renal dysfunction or disease (based on calculated creatinine clearance less than 45 mL/min/1.73 m2) at Screening.
  • Alanine aminotransferase level greater than 2.0 times the upper limit of normal, active liver disease, or jaundice at Screening.
  • Anemia (hemoglobin less than 10.0 g per dL) or thrombocytopenia (platelet count less than 100 times 103 per uL) at screening.
  • Taking aspirin greater than 162 mg per day.
  • Abuses drugs (defined as any illicit drug use) or alcohol.
  • History of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.)
  • Currently participating in another investigational study or has participated in an investigational study within 30 days prior to Screening.
  • Any other serious disease or condition at Screening or Randomization that would compromise subject safety or make it difficult to successfully manage and follow the subject according to the protocol.
  • Requires the use of pneumatic compression post-operatively.
  • Known inherited thrombophilic disorder such as the factor V Leiden or prothrombin gene mutations or deficiencies of antithrombin, protein C, or protein S.

Trial locations and contacts

64 sites in 2 countries.

64 sites in 2 countries

United States38 sites

  • Study site

    Altoona, Pennsylvania

  • Study site

    Atlanta, Georgia

  • Study site

    Aurora, Colorado

  • Study site

    Bakersfield, California

  • Study site

    Bay Pines, Florida

  • Study site

    Birmingham, Alabama

  • Study site

    Boise, Idaho

  • Study site

    Centennial, Colorado

  • Study site

    Charleston, South Carolina

  • Study site

    Charlotte, North Carolina

  • Study site

    Cincinnati, Ohio

  • Study site

    Clearwater, Florida

  • Study site

    Dallas, Texas

  • Study site

    DeLand, Florida

  • Study site

    Denver, Colorado

  • Study site

    Fountain Valley, California

  • Study site

    Grapenne, Texas

  • Study site

    Greensboro, North Carolina

  • Study site

    Gulf Breeze, Florida

  • Study site

    Hollywood, Florida

  • Study site

    Johnstown, Pennsylvania

  • Study site

    Little Rock, Arkansas

  • Study site

    Long Beach, California

  • Study site

    Lubbock, Texas

  • Study site

    Meridian, Idaho

  • Study site

    Montclair, California

  • Study site

    Oceanside, California

  • Study site

    Phoenix, Arizona

  • Study site

    Pinellas Park, Florida

  • Study site

    San Antonio, Texas

  • Study site

    Spokane, Washington

  • Study site

    Springfield, Illinois

  • Study site

    Tamarac, Florida

  • Study site

    Towson, Maryland

  • Study site

    Tulsa, Oklahoma

  • Study site

    Tuscaloosa, Alabama

  • Study site

    Vista, California

  • Study site

    Yuba City, California

Other trials in United States

Canada26 sites

  • Study site

    Ajax, Ontario

  • Study site

    Burlington, Ontario

  • Study site

    Cambridge, Ontario

  • Study site

    Charlottetown

  • Study site

    Chatham, Ontario

  • Study site

    Dartmouth, Nova Scotia

  • Study site

    Edmonton, Alberta

  • Study site

    Fredericton, New Brunswick

  • Study site

    Greater Sudbury, Ontario

  • Study site

    Guelph, Ontario

  • Study site

    Kelowna, British Columbia

  • Study site

    Kitchener, Ontario

  • Study site

    Montreal, Quebec

  • Study site

    Newmarket, Ontario

  • Study site

    Niagra Falls, Ontario

  • Study site

    Oakville, Ontario

  • Study site

    Oshawa, Ontario

  • Study site

    Ottawa, Ontario

  • Study site

    Red Deer, Alberta

  • Study site

    Saint Catherines, Ontario

  • Study site

    Saint John, New Brunswick

  • Study site

    Sarnia, Ontario

  • Study site

    Scarborough Village, Ontario

  • Study site

    Thunder Bay, Ontario

  • Study site

    Windsor, Ontario

  • Study site

    Winnipeg, Manitoba

Other trials in Canada

About this study

Official title: A Phase 2, Randomized, Active Comparator-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of TAK-442 in Subjects Undergoing Total Knee Replacement

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.

Read the 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.

Being tested
TAK-442, Enoxaparin
Keywords
venous thromboembolism, oral anticoagulant, direct factor Xa inhibitor, total knee replacement, drug therapy
Medical subject headings
Venous Thromboembolism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAK-442Drug

    TAK-442 40 mg, tablets, orally, once daily for up to 10 days.

  • TAK-442Drug

    TAK-442 80 mg, tablets, orally, once daily for up to 10 days.

  • TAK-442Drug

    TAK-442 10 mg, tablets, orally, twice daily for up to 10 days.

  • TAK-442Drug

    TAK-442 20 mg, tablets, orally, twice daily for up to 10 days.

  • TAK-442Drug

    TAK-442 40mg, tablets, orally, twice daily for up to 10 days.

  • TAK-442Drug

    TAK-442 80 mg, tablets, orally, twice daily for up to 10 days.

  • EnoxaparinDrug

    Enoxaparin 30 mg, syringe, subcutaneous injection, twice daily for up to 10 days.

Study groups in NCT00641732
Study groupRoleWhat they receive
TAK-442 40 mg QDExperimentalNot described
Receives: Drug: TAK-442
TAK-442 80 mg QDExperimentalNot described
Receives: Drug: TAK-442
TAK-442 10 mg BIDExperimentalNot described
Receives: Drug: TAK-442
TAK-442 20 mg BIDExperimentalNot described
Receives: Drug: TAK-442
TAK-442 40 mg BIDExperimentalNot described
Receives: Drug: TAK-442
TAK-442 80 mg BIDExperimentalNot described
Receives: Drug: TAK-442
Enoxaparin 30 mg BIDActive comparatorNot described
Receives: Drug: Enoxaparin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite evaluation of All-Cause Mortality, Symptomatic and Asymptomatic Deep Vein Thrombosis and Symptomatic Pulmonary Embolism.

    Measured: Day 10.

  2. Incidence of Major Bleeding.

    Measured: Day 10.

Secondary outcomes (6)

  1. Evaluation of Major Venous Thromboembolism (composite of Symptomatic or Asymptomatic Proximal Deep Vein Thrombosis, Symptomatic Objectively Confirmed Pulmonary Embolism, and Venous Thromboembolism-Related Death).

    Measured: Day 10.

  2. Evaluation of Symptomatic Venous Thromboembolism.

    Measured: Day 10.

  3. Evaluation of Proximal Deep Vein Thrombosis.

    Measured: Day 10.

  4. Evaluation of Distal Deep Vein Thrombosis.

    Measured: Day 10.

  5. Evaluation of clinically significant Non-Major Bleeding events.

    Measured: Day 10.

  6. Evaluation of Minor Bleeding events.

    Measured: Day 10.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2008 (estimated)
  2. Study startOct 2007
  3. Primary completionOct 2008
  4. Study completionOct 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,045 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00641732
Sponsor's protocol ID
TAK-442_201
Other IDs
U1111-1115-9359
Status last verified
Mar 2016
First submitted
18 Mar 2008
Last updated
13 Apr 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Weitz JI, Cao C, Eriksson BI, Fisher W, Kupfer S, Raskob G, Spaeder J, Turpie AG. A dose-finding study with TAK-442, an oral factor Xa inhibitor, in patients undergoing elective total knee replacement surgery. Thromb Haemost. 2010 Dec;104(6):1150-7. doi: 10.1160/TH10-05-0273. Epub 2010 Sep 30.

    PubMed 20886185

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TAK-442 and Enoxaparin in people with Venous Thromboembolism, run by Takeda at 64 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite evaluation of All-Cause Mortality, Symptomatic and Asymptomatic Deep Vein Thrombosis and Symptomatic Pulmonary Embolism. (time frame: Day 10.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00641732, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2016.

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