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Active Comparator-Controlled Study to Assess Safety and Efficacy of ISIS-FXIRx in Total Knee Arthroplasty

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01713361
Recruitment Status : Completed
First Posted : October 24, 2012
Last Update Posted : August 27, 2014
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Brief Summary:

The purpose of this study is:

  • To assess the safety and efficacy profile of ISIS-FXIRx, including incidence of bleeding and VTE, in patients undergoing total knee arthroplasty.
  • To compare the efficacy and safety profile of ISIS-FXIRx in patients who achieve less than or equal to 0.2 U/mL FXI activity levels to that of enoxaparin.

Condition or disease Intervention/treatment Phase
Venous Thromboembolism Drug: ISIS-FXIRx Dose #2 Drug: ISIS-FXIRx Dose #3 Drug: Enoxaparin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 315 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: An Open-label, Randomized, Active Comparator-Controlled, Adaptive Parallel-group Phase 2 Study to Assess the Safety and Efficacy of Multiple Doses of ISIS 416858 Administered Subcutaneously to Patients Undergoing Total Knee Arthroplasty
Study Start Date : October 2012
Actual Primary Completion Date : May 2014
Actual Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Knee Replacement

Arm Intervention/treatment
Experimental: ISIS-FXIRx Dose 2
Group B: ISIS-FXIRx Dose #2
Drug: ISIS-FXIRx Dose #2
Group B: ISIS-FXIRx dose #2 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
Other Name: ISIS-FXIRx

Experimental: ISIS-FXIRx Dose 3
Group C: ISIS-FXIRx Dose #3
Drug: ISIS-FXIRx Dose #3
Group C: ISIS-FXIRx dose #3 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
Other Name: ISIS-FXIRx

Active Comparator: Enoxaparin
Enoxaparin (40mg)
Drug: Enoxaparin
Enoxaparin (40mg) will be administered by subcutaneous injection the evening prior to total knee arthroplasty (optionally), 6 to 8 hours after surgery, followed by daily injections for at least 8 additional days post surgery (a total of at least 9 consecutive days). [Except for Canadian region, in which the subcutaneous injection of enoxaparin the evening prior to total knee arthroplasty is expected, resulting in a total of at least 10 consecutive days of enoxaparin.]
Other Names:
  • Lovenox
  • Clexane

Primary Outcome Measures :
  1. Primary efficacy outcome [ Time Frame: up to 12 days post-surgery ]
    Composite of asymptomatic DVT (via bilateral venography), and symptomatic VTE, fatal PE, and unexplained death.

Secondary Outcome Measures :
  1. Secondary efficacy outcome [ Time Frame: 1st dose to up to Day 76 ]
    All DVTs and PEs up to 4 weeks after bilateral venography

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Give written informed consent
  • Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal. Males must be surgically sterile, abstinent, or if engaged in sexual relations of child-bearing potential, must use contraception
  • Undergoing elective, primary unilateral total knee arthroplasty

Exclusion Criteria:

  • Body weight <50 kg
  • Patients at increased risk of bleeding. History of intracranial or intraocular bleeding. History of gastrointestinal and/or endoscopically verified ulcer disease within the past year.
  • History of excessive intra- or direct post operative bleeding or a traumatic spinal or epidural anesthesia
  • Brain, spinal, or ophthalmologic surgery within the past 3 months
  • History of clinically significant liver disease in the past year
  • Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values

    • aPTT or PT or INR >ULN
    • Factor IX activity <LLN
    • Factor VIII activity, vWF antigen or Ristocetin cofactor activity <0.5 U/mL
    • FXI activity <0.3 U/mL
    • Urine protein or blood persistently positive by dipstick. In the event of positive test results, eligibility may be confirmed with urine microscopy or 24 hour urine protein measurement as applicable
    • ALT or AST >1.5 x ULN
    • Total bilirubin >ULN
    • Platelet count <150,000 (or history of thrombocytopenia)
  • Hypersensitivity to enoxaparin
  • Anticipated concomitant use of anticoagulants/antiplatelet agents or the NSAID nimesulide that may affect study outcome or any other drug influencing coagulation (except low dose aspirin and short acting NSAIDs with a half-life <20 hours) at least 7 days before surgery or during treatment with ISIS Rx.
  • Anticipated use of indwelling intrathecal or epidural catheters
  • Anemia at Screening
  • Have any other conditions which could interfere with the patient participating in or completing the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01713361

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Isis Investigational Site
Plovdiv, Bulgaria, 4002
Isis Investigational Site
Rousse, Bulgaria, 7002
Isis Investigational Site
Sofia, Bulgaria, 1527
Canada, Ontario
Isis Investigational Site
Ajax, Ontario, Canada, LIS 2J4
Isis Investigational Site
Oshawa, Ontario, Canada, LIG 2B9
Isis Investigational Site
Adazi, Latvia, LV 2164
Isis Investigational Site
Riga, Latvia, LV 1004
Isis Investigational Site
Valmiera, Latvia, LV4201
Russian Federation
Isis Investigational Site
Chelyabinsk, Russian Federation, 454026
Isis Investigational Site
Orenburg, Russian Federation, 460000
Isis Investigational Site
Saint Petersburg, Russian Federation, 193312
Isis Investigational Site
Saint Petersburg, Russian Federation, 194291
Isis Investigational Site
Saint Petersburg, Russian Federation, 194354
Isis Investigational Site
Samara, Russian Federation, 443095
Isis Investigational Site
Yaroslavl, Russian Federation, 150047
Isis Investigational Site
Cherkassy, Ukraine, 18009
Isis Investigational Site
Ivano-Frankivsk, Ukraine, 76000
Isis Investigational Site
Kharkiv, Ukraine, 61024
Isis Investigational Site
Kyiv, Ukraine, 01107
Isis Investigational Site
Odessa, Ukraine, 65025
Isis Investigational Site
Sevastopol, Ukraine, 99018
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
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Study Director: Sanjay Bhanot, MD, PhD VP, Clinical Development, Isis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01713361    
Other Study ID Numbers: ISIS 416858-CS3
First Posted: October 24, 2012    Key Record Dates
Last Update Posted: August 27, 2014
Last Verified: August 2014
Keywords provided by Ionis Pharmaceuticals, Inc.:
total knee arthroplasty
Additional relevant MeSH terms:
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Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action