Venous Thromboembolism
Conditions
Keywords
total knee arthroplasty, Prophylaxis
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.
Interventions
DRUGISIS-FXIRx Dose #2
Group B: ISIS-FXIRx dose #2 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
DRUGISIS-FXIRx Dose #3
Group C: ISIS-FXIRx dose #3 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
DRUGEnoxaparin
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). \[Except for Canadian region, in which the subcutaneous injection of enoxaparin the evening prior to total knee arthroplasty is expected, resulting in a total of at least 10 consecutive days of enoxaparin.\]
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary efficacy outcome | up to 12 days post-surgery | Composite of asymptomatic DVT (via bilateral venography), and symptomatic VTE, fatal PE, and unexplained death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary efficacy outcome | 1st dose to up to Day 76 | All DVTs and PEs up to 4 weeks after bilateral venography |
Countries
Bulgaria, Canada, Latvia, Russia, Ukraine
Outcome results
None listed