Knee ArthropathyNCT04058743
Nickel Sensitivity
A study testing TKA with nickel free components and TKA with standard cobalt chromium components in people with Knee Arthropathy and Allergic Reaction, run by Rush University Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to compare clinical outcomes of patients with self reported nickel sensitivity undergoing primary total knee arthroplasty (TKA) with conventional, standard-of-care vs nickel-free implants. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Knee Arthropathy, Allergic Reaction
- What is being tested?
- TKA with nickel free components and TKA with standard cobalt chromium components
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Sep 2019to 21 Dec 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing primary TKA for the diagnosis of osteoarthritis or inflammatory arthritis with self-reported nickel allergy. Patients are routinely asked about nickel sensitivity as a part of the standard pre operative questionnaire already in place.
Who cannot join
- Patients less than 18 years of age
- Patients undergoing revision TKA
- Non english speaking patients
- Patient who have medical comorbidities that prevent elective TKA
Trial locations and contacts
1 site in 1 country.
United States1 site
Rush University medical Center
Chicago, Illinois, 60612
About this study
Official title: Effect of Nickel Sensitivity on Patient Reported Outcomes After Total Knee Arthroplasty
The purpose of this study is to compare clinical outcomes of patients with self reported nickel sensitivity undergoing primary total knee arthroplasty (TKA) with conventional, standard-of-care vs nickel-free implants. The hypothesis is that patients with a self-reported nickel sensitivity will have similar patient reported outcome scores compared to those patients without reported nickel sensitivity. Therefor the anticipation is for there to be no differences in other clinical outcome measures or functional outcome scores between the two cohorts.
Read the detailed description
Metal implants are a mainstay of orthopedic treatment, and a variety of metal implants have been utilized for more than 40 years. Total knee replacement implants have been comprised of a variety of metal, ceramic, and plastic components. Current standard-of-care for TKA employs a cobalt chrome alloy femoral implant that articulates with the polyethylene surface of the tibial component. This cobalt chrome alloy can contain up to 1% nickel.
While most patients report pain relief and satisfaction after TKA, there are a number of complications that can result. Infection, component loosening, polyethylene wear, and malalignment are common reasons for persistent pain after TKA. Metal sensitivity as a cause of persistent pain after total joint arthroplasty is a controversial topic. Cutaneous metal hypersensitivity has a prevalence of approximately 10-15% in the general population, with nickel being the most common metal sensitizer with a prevalence near 14%. Cross reactivity with cobalt chrome and nickel is very common.
The role of metal allergy in orthopedic surgery and total joint arthroplasty is a poorly understood relationship. The cause and effect relationship of this process has not been delineated - it is unclear if the immunogenic response causes implant failure, or implant failure releases hapten particles with lead to a deep tissue reaction.
Metal hypersensitivity after TKA is a rarely documented phenomenon without specific diagnostic criteria, and there is much debate on if this is even a true diagnosis. The two most commonly described presentations include 1) dermatitis or 2) persistent painful synovitis although these have only been described in case reports without defined diagnostic criteria. Few reports exist regarding the diagnosis and management of these conditions. There is no reliable or generally accepted test to predict allergy to total joint replacement components. Patient history of metal sensitivity is not a reliable indicator of TJA outcome, as 25% of patients with well-functioning TJA implants have a reported metal allergy. A nickel or metal sensitivity has not been statistically identified as a risk factor for any specific cutaneous or deep tissue reaction, complication, or poor outcome after TKA.
Typically, metal sensitivity patients are identified after having a superficial skin reaction after dermal contact with a metal. Nickel containing jewelry is a common precipitator. The true diagnosis of skin sensitivity to metal is diagnosed by cutaneous patch testing, often employed by dermatologists. This test is not specific or sensitive for the diagnosis of deep tissue metal sensitivity. In a case control study, Granchi et al followed 94 patients without metal implants, with stable painless TKA, and with TKA and evidence of loosening. The study found no predictive value in dermal patch testing for metal hypersensitivity and the stability of TKA implants. Verma et al followed 30 patients with dermatitis following TKA. Fifteen were available for patch testing, but only seven patients tested 1+ or 2+ reaction to a metal. Dermatitis in all patients cleared with topical steroid. The relationship between positive patch testing and clinically relevant deep tissue reactions has not been delineated.
Lymphocyte transformation testing (LTT) or lymphocyte stimulation testing involves obtaining patient lymphocytes from a peripheral blood draw, and testing reactivity with a variety of antigens, including cobalt, nickel, and zirconium. Many argue that this test better replicates the sensitization that occurs in deep tissue after TJA, but its correlation to outcomes after arthroplasty has never been shown. Niki et al preformed lymphocyte stimulating testing on 92 patients (108 knees) undergoing primary TKA. 24 patients tested positive for metal hypersensitivity. Ultimately only five went on to develop dermatitis. Thus the clinical significance of positive results of lymphocyte stimulation testing is still unknown.
Additionally, serum metal levels are often elevated in patients with well-functioning TKA, and thus this test is not recommended for diagnosis of metal sensitivity. As a result, other causes such as infection, malalignment, aseptic loosening, referred pain, or systemic pain syndromes should all evaluated in persistently painful TKA.
At this time, metal sensitivity is not considered a significant cause of TKA failure. As the literature is inconclusive on identification and management of patients with metal hypersensitivity there is currently no indication for metal allergy screening prior to TKA. No study has found that patients with a previously known metal sensitivity have an increase rate of failure or revision TKA compared to those without. None of the major academic orthopedic societies recommend routine use of nickel free implants. There is currently no data showing correlation between nickel allergy and poor outcomes after total joint replacement with nickel containing implants. While non-nickel containing TKA implants have been developed, there is no evidence-based criteria for their use in specific patient populations. The goal of this study is to compare Knee Society Scores in patients with self-reported metal allergy who receive standard of care nickel containing implants vs oxidized zirconium nickel free implants for primary TKA.
- Conditions
- Knee Arthropathy, Allergic Reaction
- Being tested
- TKA with nickel free components, TKA with standard cobalt chromium components
- Medical subject headings
- Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TKA with nickel free componentsDevice
Patients will be randomized to receive either the standard cobalt chromium components or nickel free components
TKA with standard cobalt chromium componentsDevice
Patients will be randomized to receive either the standard cobalt chromium components or nickel free components
| Study group | Role | What they receive |
|---|---|---|
| TKA with standard cobalt chromium components | Active comparator | Patients randomized to this group will receive the standard cobalt chromium components in their total knee arthroplasty Receives: Device: TKA with standard cobalt chromium components |
| TKA with nickel free components | Experimental | Patients randomized to this group will receive nickel free components in their total knee arthroplasty Receives: Device: TKA with nickel free components |
What is being measured
The primary outcome is the main question the study is designed to answer.
Knee Society Score (KSS)
Change from pre operative to post operative Knee Society Scores at various time intervals. KSS is scored 0-100 with 100 being a perfectly functioning knee and is used as a gauge of success for a knee replacement.
Measured: 3 weeks
Secondary outcomes (5)
Number of Participants With Complications
Any peri- or postoperative complications will be recorded including DVT/PE, return to the OR within 90 days, readmission within 90 days, superficial infection, deep infection, dermatitis, periprosthetic fracture, cerebrovascular accident/transient ischemic attack.
Measured: 90 days
Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR.)
Postoperative Knee Injury and Osteoarthritis Outcome Scores (KOOS JR) will also be recorded. This score is 0-100 with 100 being a perfectly functioning knee.
Measured: 3 weeks
Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR.)
Postoperative Knee Injury and Osteoarthritis Outcome Scores (KOOS JR) will also be recorded. This score is 0-100 with 100 being a perfectly functioning knee.
Measured: 6 weeks
Number of Participants With Proper Component Alignment and *Without* Any Signs of Loosening
Radiographic review was done at 3 weeks after surgery to assess for component alignment and review for signs of loosening.
Measured: 3 weeks after surgery
Number of Participants With Proper Component Alignment and *Without* Any Signs of Loosening
x-rays done at 6 weeks after surgery were evaluated (standing AP, skiers and lateral views)
Measured: 6 weeks after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2019
- Study start27 Sep 2019
- Primary completion11 Dec 2024
- Study completion21 Dec 2024
Why it stopped: We have decided to stop the study due to lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Knee ArthropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective randomized controlled trial with two groups: Total knee replacement with standard cobalt chromium components vs Total Knee Replacements with nickel free components.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Craig J Della Valle, MD, Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04058743
- Sponsor's protocol ID
- 18112703
- Status last verified
- Apr 2026
- First submitted
- 14 Aug 2019
- Last updated
- 1 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Nickel Sensitivity on Patient Reported Outcomes After Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT04058743
- Acronym / sponsor ID
- 18112703
- Conditions
- Knee Arthropathy, Allergic Reaction
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: We have decided to stop the study due to lack of enrollment
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Study start
- 27 Sep 2019 (actual)
- Primary completion
- 11 Dec 2024 (actual)
- Study completion
- 21 Dec 2024 (actual)
- First posted
- 15 Aug 2019 (actual)
- Results
- Posted 1 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare clinical outcomes of patients with self reported nickel sensitivity undergoing primary total knee arthroplasty (TKA) with conventional, standard-of-care vs nickel-free implants. The hypothesis is that patients with a self-reported nickel sensitivity will have similar patient reported outcome scores compared to those patients without reported nickel sensitivity. Therefor the anticipation is for there to be no differences in other clinical outcome measures or functional outcome scores between the two cohorts.
Detailed description
Metal implants are a mainstay of orthopedic treatment, and a variety of metal implants have been utilized for more than 40 years. Total knee replacement implants have been comprised of a variety of metal, ceramic, and plastic components. Current standard-of-care for TKA employs a cobalt chrome alloy femoral implant that articulates with the polyethylene surface of the tibial component. This cobalt chrome alloy can contain up to 1% nickel.
While most patients report pain relief and satisfaction after TKA, there are a number of complications that can result. Infection, component loosening, polyethylene wear, and malalignment are common reasons for persistent pain after TKA. Metal sensitivity as a cause of persistent pain after total joint arthroplasty is a controversial topic. Cutaneous metal hypersensitivity has a prevalence of approximately 10-15% in the general population, with nickel being the most common metal sensitizer with a prevalence near 14%. Cross reactivity with cobalt chrome and nickel is very common.
The role of metal allergy in orthopedic surgery and total joint arthroplasty is a poorly understood relationship. The cause and effect relationship of this process has not been delineated - it is unclear if the immunogenic response causes implant failure, or implant failure releases hapten particles with lead to a deep tissue reaction.
Metal hypersensitivity after TKA is a rarely documented phenomenon without specific diagnostic criteria, and there is much debate on if this is even a true diagnosis. The two most commonly described presentations include 1) dermatitis or 2) persistent painful synovitis although these have only been described in case reports without defined diagnostic criteria. Few reports exist regarding the diagnosis and management of these conditions. There is no reliable or generally accepted test to predict allergy to total joint replacement components. Patient history of metal sensitivity is not a reliable indicator of TJA outcome, as 25% of patients with well-functioning TJA implants have a reported metal allergy. A nickel or metal sensitivity has not been statistically identified as a risk factor for any specific cutaneous or deep tissue reaction, complication, or poor outcome after TKA.
Typically, metal sensitivity patients are identified after having a superficial skin reaction after dermal contact with a metal. Nickel containing jewelry is a common precipitator. The true diagnosis of skin sensitivity to metal is diagnosed by cutaneous patch testing, often employed by dermatologists. This test is not specific or sensitive for the diagnosis of deep tissue metal sensitivity. In a case control study, Granchi et al followed 94 patients without metal implants, with stable painless TKA, and with TKA and evidence of loosening. The study found no predictive value in dermal patch testing for metal hypersensitivity and the stability of TKA implants. Verma et al followed 30 patients with dermatitis following TKA. Fifteen were available for patch testing, but only seven patients tested 1+ or 2+ reaction to a metal. Dermatitis in all patients cleared with topical steroid. The relationship between positive patch testing and clinically relevant deep tissue reactions has not been delineated.
Lymphocyte transformation testing (LTT) or lymphocyte stimulation testing involves obtaining patient lymphocytes from a peripheral blood draw, and testing reactivity with a variety of antigens, including cobalt, nickel, and zirconium. Many argue that this test better replicates the sensitization that occurs in deep tissue after TJA, but its correlation to outcomes after arthroplasty has never been shown. Niki et al preformed lymphocyte stimulating testing on 92 patients (108 knees) undergoing primary TKA. 24 patients tested positive for metal hypersensitivity. Ultimately only five went on to develop dermatitis. Thus the clinical significance of positive results of lymphocyte stimulation testing is still unknown.
Additionally, serum metal levels are often elevated in patients with well-functioning TKA, and thus this test is not recommended for diagnosis of metal sensitivity. As a result, other causes such as infection, malalignment, aseptic loosening, referred pain, or systemic pain syndromes should all evaluated in persistently painful TKA.
At this time, metal sensitivity is not considered a significant cause of TKA failure. As the literature is inconclusive on identification and management of patients with metal hypersensitivity there is currently no indication for metal allergy screening prior to TKA. No study has found that patients with a previously known metal sensitivity have an increase rate of failure or revision TKA compared to those without. None of the major academic orthopedic societies recommend routine use of nickel free implants. There is currently no data showing correlation between nickel allergy and poor outcomes after total joint replacement with nickel containing implants. While non-nickel containing TKA implants have been developed, there is no evidence-based criteria for their use in specific patient populations. The goal of this study is to compare Knee Society Scores in patients with self-reported metal allergy who receive standard of care nickel containing implants vs oxidized zirconium nickel free implants for primary TKA.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Prospective randomized controlled trial with two groups: Total knee replacement with standard cobalt chromium components vs Total Knee Replacements with nickel free components.
| Arm | Type | Receives |
|---|---|---|
| TKA with standard cobalt chromium components | Active comparator | Device: TKA with standard cobalt chromium componentsPatients randomized to this group will receive the standard cobalt chromium components in their total knee arthroplasty |
| TKA with nickel free components | Experimental | Device: TKA with nickel free componentsPatients randomized to this group will receive nickel free components in their total knee arthroplasty |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients undergoing primary TKA for the diagnosis of osteoarthritis or inflammatory arthritis with self-reported nickel allergy. Patients are routinely asked about nickel sensitivity as a part of the standard pre operative questionnaire already in place.
Key exclusion criteria (4 listed)
- Patients less than 18 years of age
- Patients undergoing revision TKA
- Non english speaking patients
- Patient who have medical comorbidities that prevent elective TKA
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TKA with nickel free componentsPatients will be randomized to receive either the standard cobalt chromium components or nickel free components | Device | TKA with nickel free components |
| TKA with standard cobalt chromium componentsPatients will be randomized to receive either the standard cobalt chromium components or nickel free components | Device | TKA with standard cobalt chromium components |
Primary outcome
Knee Society Score (KSS)
Time frame: 3 weeks
Change from pre operative to post operative Knee Society Scores at various time intervals. KSS is scored 0-100 with 100 being a perfectly functioning knee and is used as a gauge of success for a knee replacement.
5 secondary outcomes
Number of Participants With Complications
Time frame: 90 days
Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR.)
Time frame: 3 weeks
Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR.)
Time frame: 6 weeks
Number of Participants With Proper Component Alignment and *Without* Any Signs of Loosening
Time frame: 3 weeks after surgery
Number of Participants With Proper Component Alignment and *Without* Any Signs of Loosening
Time frame: 6 weeks after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TKA with nickel free components and TKA with standard cobalt chromium components in people with Knee Arthropathy and Allergic Reaction, run by Rush University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Knee Society Score (KSS) (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.