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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Isis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01713361
First received: October 4, 2012
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Venous Thromboembolism
Drug: ISIS-FXIRx Dose #2
Drug: ISIS-FXIRx Dose #3
Drug: Enoxaparin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Isis Pharmaceuticals:

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


Secondary Outcome Measures:
  • Secondary efficacy outcome [ Time Frame: 1st dose to up to Day 76 ] [ Designated as safety issue: Yes ]
    All DVTs and PEs up to 4 weeks after bilateral venography


Enrollment: 315
Study Start Date: October 2012
Study Completion Date: August 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01713361

Locations
Bulgaria
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
Latvia
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, 194354
Isis Investigational Site
Saint Petersburg, Russian Federation, 194291
Isis Investigational Site
Saint Petersburg, Russian Federation, 193312
Isis Investigational Site
Samara, Russian Federation, 443095
Isis Investigational Site
Yaroslavl, Russian Federation, 150047
Ukraine
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
Isis Pharmaceuticals
Investigators
Study Director: Sanjay Bhanot, MD, PhD VP, Clinical Development, Isis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Isis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01713361     History of Changes
Other Study ID Numbers: ISIS 416858-CS3
Study First Received: October 4, 2012
Last Updated: August 25, 2014
Health Authority: Canada: Health Canada
Russia: Ministry of Health of the Russian Federation
Ukraine: Ministry of Health
Latvia: State Agency of Medicines
Bulgaria: Ministry of Health

Keywords provided by Isis Pharmaceuticals:
total knee arthroplasty
Prophylaxis

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Thrombosis
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2014