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

NCT ID: NCT01713361

Last Updated: 2014-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

315 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2014-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Venous Thromboembolism

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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ISIS-FXIRx Dose 2

Group B: ISIS-FXIRx Dose #2

Group Type EXPERIMENTAL

ISIS-FXIRx Dose #2

Intervention Type DRUG

Group B: ISIS-FXIRx dose #2 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.

ISIS-FXIRx Dose 3

Group C: ISIS-FXIRx Dose #3

Group Type EXPERIMENTAL

ISIS-FXIRx Dose #3

Intervention Type DRUG

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

Enoxaparin

Enoxaparin (40mg)

Group Type ACTIVE_COMPARATOR

Enoxaparin

Intervention Type DRUG

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). \[Except for Canadian region, in which the subcutaneous injection of enoxaparin the evening prior to total knee arthroplasty is expected, resulting in a total of at least 10 consecutive days of enoxaparin.\]

Interventions

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ISIS-FXIRx Dose #2

Group B: ISIS-FXIRx dose #2 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.

Intervention Type 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.

Intervention Type 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). \[Except for Canadian region, in which the subcutaneous injection of enoxaparin the evening prior to total knee arthroplasty is expected, resulting in a total of at least 10 consecutive days of enoxaparin.\]

Intervention Type DRUG

Other Intervention Names

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ISIS-FXIRx ISIS-FXIRx Lovenox Clexane

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sanjay Bhanot, MD, PhD

Role: STUDY_DIRECTOR

VP, Clinical Development, Isis Pharmaceuticals

Locations

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Isis Investigational Site

Plovdiv, , Bulgaria

Site Status

Isis Investigational Site

Rousse, , Bulgaria

Site Status

Isis Investigational Site

Sofia, , Bulgaria

Site Status

Isis Investigational Site

Ajax, Ontario, Canada

Site Status

Isis Investigational Site

Oshawa, Ontario, Canada

Site Status

Isis Investigational Site

Ādaži, , Latvia

Site Status

Isis Investigational Site

Riga, , Latvia

Site Status

Isis Investigational Site

Valmiera, , Latvia

Site Status

Isis Investigational Site

Chelyabinsk, , Russia

Site Status

Isis Investigational Site

Orenburg, , Russia

Site Status

Isis Investigational Site

Saint Petersburg, , Russia

Site Status

Isis Investigational Site

Saint Petersburg, , Russia

Site Status

Isis Investigational Site

Saint Petersburg, , Russia

Site Status

Isis Investigational Site

Samara, , Russia

Site Status

Isis Investigational Site

Yaroslavl, , Russia

Site Status

Isis Investigational Site

Cherkassy, , Ukraine

Site Status

Isis Investigational Site

Ivano-Frankivsk, , Ukraine

Site Status

Isis Investigational Site

Kharkiv, , Ukraine

Site Status

Isis Investigational Site

Kyiv, , Ukraine

Site Status

Isis Investigational Site

Odesa, , Ukraine

Site Status

Isis Investigational Site

Sevastopol, , Ukraine

Site Status

Countries

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Bulgaria Canada Latvia Russia Ukraine

References

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Buller HR, Bethune C, Bhanot S, Gailani D, Monia BP, Raskob GE, Segers A, Verhamme P, Weitz JI; FXI-ASO TKA Investigators. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med. 2015 Jan 15;372(3):232-40. doi: 10.1056/NEJMoa1405760. Epub 2014 Dec 7.

Reference Type DERIVED
PMID: 25482425 (View on PubMed)

Other Identifiers

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ISIS 416858-CS3

Identifier Type: -

Identifier Source: org_study_id

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