Medical deviceKnee ImplantPresented by Valeria A. AguirreFellow at Academy of Applied Pharmaceutical Sciences, AAPS

IntroductionDescription of the deviceIndications Risks and complications Risks/ BenefitsCostClinical Trials

Introduction:

Although replacing the total knee joint is the most common procedure, some people can benefit from just a partial knee replacement.Implants are made of metal alloys, ceramic material, or strong plastic parts, and can be joined to bones by acrylic cement.Several manufacturers make knee implants and there are more than 150 knee replacement designs on the market today.

Normal Knee anatomy and function:

Knee implant componentsThe lower ends of the femurThe top surface of the tibiaThe back surface of the patella.

Implant materials:Metal parts: titanium or cobalt-chromium based alloys.

Plastic part: ultra high molecular weight polyethyleneCemented fixation: polymethylmethacrylate

hybrid fixation: femoral component: without cementtibial and patellar components: with cement.

Indications for Knee Replacement Surgery:

Knee pain that hinders walking, climbing stairs, or getting in and out of a chairKnee pain that interferes with sleep or does not subside with restInability to cope with side effects of pain relief medicationKnee swelling that does not respond to treatment and that limits bending or straightening the kneeSignificant bowing in or out of the kneeOsteoarthritis severe cases

Risk and complications of replacement surgery

Complications from Anesthesia:Most common side effects:vomitingdizzinessshiveringsore throataches and painsdiscomfortdrowsiness

Negative reactions:dental traumacroup (swelling of the windpipe)allergic reactions to latexwheezingvocal cord injurystomach problemsinjuries to arteries, veins, or nerves

Blood Clots:deep vein thrombosis (DVT) andpulmonary embolism (PE)

typically occur within two weeks of surgery

they can also take place within a few hours or even in the operating roomsmoking or obesity, increase the risk.

Infection:

The number of people who get an infection after a knee replacement is very lowPeople with rheumatoid arthritis or diabetes have a greater risk of infection in the weeks following a procedure because of their altered immune systemInfection in another part of the body at the time of a knee operation, could lead to an infection in the knee months or even years later

Complications from a Transfusion

hivesfeverchillsshortness of breathred urineSigns and symptoms of an adverse transfusion reaction usually occur within 24 hours

Allergy to Metal ComponentsWound and Bleeding ComplicationsArtery InjuriesNerve or Neurovascular DamageKnee Stiffness and Loss of Motion in the Knee

Prosthesis Problems and Implant Failure

Improper placement or a malfunction of the implant:

-new knee might not bend properly-the prosthesis might loosen from the bone over the long-term-Other parts in the artificial knee could break downThese failures are extremely rareRevision surgery is usually required to fix the problem when this does happen

Mortality:

The risk of death from knee replacement is very low, but it does occur

A 2010 study published in theJournal of Bone and Joint Surgeryestimated the risk of mortality to be 0.1 percent

The risk is highest during the first month after surgery

Risks/ BenefitsBenefits:Pain reliefImprove joint functionRisks:The same dangers as other major surgeriesThe new joint may not work as well as hopedImplant becomes loose or dislocates

Price Estimates

Including room fee, nurse fee, food, pre-op tests, medical supplies, medication, operating room fee, x-rays, and consulation

CountryPrice (USD)United States$45,000-$60,000Singapore$18,000-$22,500Thailand$12,000-$14,200Taiwan$9,000 $10,100India$7,000 $11,200

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Cost of a knee replacement in selected countries as of 2015 (in U.S. dollars)

Clinical Trial: Phase-4 Study ConforMIS iTotal (CR)Knee ReplacementSystem Versus Off-the-ShelfReplacement

Sponsor: ConforMIS, Inc.http://www.conformis.com/ClinicalTrials.gov Identifier: NCT02494544

Traditional knee replacements come in standardized sizes which require shaving the femur bone to fit the implantiTotal knee replacement implants are custom made to fit each individual patient

Purpose:Patients will be randomized to either ConforMIS iTotal Knee Replacement or Off the Shelf knee replacement

The patient will conduct functional testing and answer questionnaires

The results will compare the ConforMIS iTotal with an Off the Shelf Knee replacement

Study Type:InterventionalStudy Design:Allocation:Randomized

EndpointClassification:EfficacyStudy

InterventionModel:ParallelAssignment

Masking:DoubleBlind

PrimaryPurpose:BasicScience

Estimated Enrollment: 800Study Start Date: July 2015Estimated Study Completion Date: August 2025Estimated Primary Completion Date:August 2016 (primary outcome measure)

Primary Outcome Measures:Functional Testing after1 year

Comparing the functional testing differences between iTotal and off the shelf

Secondary Outcome Measures:Patient reported outcome using questionnaires

Incidents of major procedure-related and device related complications

Post-operative limb alignment based using x-ray

Inclusion Criteria:

Clinical condition for the use of iTotal CR

Osteoarthritis

> 18 years of age

Exclusion Criteria:Subject will require a simultaneous bilateral procedureOther lower extremity surgery within 1 yearSevere (> 15) fixed valgus or varus deformitySevere (> 15) extension deficitSevere instability due to advanced loss of osteochondral structureLoss of bone or musculature, osteoporosis, neuromuscular or vascular compromise in the area of the joint to be operated on to an extent that the procedure is unjustifiedInsufficient bone stock on the femoral or tibial surfacesContralateral knee replacement surgery within the past 6 monthsBMI > 40

Active malignancyPoorly controlled diabetes ImmunocompromisedOther physical disability affecting the hips, spine, or contralateral knee that limits functionDisabling chronic pain with narcotic dependenceCompromised PCL or collateral ligamentPrior history of failed implant surgeryPrior history of failed high tibial osteotomy (HTO)Participation in another clinical study which would confound resultsInability to complete the protocol

Investigational Testing Authorization:

https://www.clinicaltrials.gov/ct2/show/NCT02255383?term=new+knee+implant&rank=26http://www.zimmer.com/medical-professionals/products/knee/persona-knee.htmlClinical Trial: NCT02255383

References:http://www.drugwatch.com/knee-replacement/complications/http://www.healthline.com/health/total-knee-replacement-surgery/risks-complications#1http://orthoinfo.aaos.org/topic.cfm?topic=a00221http://www.healthcommunities.com/orthopedic-surgery/knee-replacement-indications.shtmlhttp://www.webmd.com/osteoarthritis/knee-hip-replacement-14/joint-replacement-risks-benefitshttp://www.kneereplacementcost.com/http://www.statista.com/statistics/189975/cost-of-a-knee-replacement-in-various-countries/https://clinicaltrials.gov/http://www.alliancehealthpryor.com/medical-services/conformis-total-knee-replacement-surgery

Thank you!