Arthritis, Failure of Total HipNCT02208271
A Validated Necrosis Assay to Determine the Need for Revision Surgery in Metal-on-metal Total Hip Arthroplasty
An observational study of Arthritis, Failure of Total Hip, run by OrthoCarolina Research Institute, Inc. at 1 site in United States.
Trial summary
The purpose of the study is to develop a biomarker assay to be used as a diagnostic tool for adverse local tissue reaction, or tissue necrosis, in a metal on metal total hip replacement. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Failure of Total Hip
- How many people
- 174 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Aug 2014to 12 Aug 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: A convenience sample of a total of 100 hip patients will be enrolled at orthopedic clinics.
Who may be able to join
- Patients presenting for a metal on metal hip revision who have cobalt and chromium metal ion levels tested within 6 months of the date of the planned revision surgery.
- Patients presenting for a metal on poly hip revision
- Revision hip patients must be greater than one year postoperative
- The diagnosis at the time of the index, or primary, hip replacement was osteoarthritis.
- Patients who have hip osteoarthritis but have not had a total hip surgery (control)
Who cannot join
- Patients presenting for a metal on metal hip revision who have cobalt and chromium metal ion levels tested >6 months of the date of the planned revision
- Patients with a total hip on the contralateral side.
- Patients with a prior history of periprosthetic infection
- Revision cases where the diagnosis at the time of the index, or primary, hip replacement was not osteoarthritis.
- Prisoners
- Patients not willing to consent for the proposed treatment
Show all 10Show fewer
- Patients with an altered mental status
- Active, concurrent metastatic infection
- Active, superficial infection
- Patients presenting for a metal on poly hip revision to treat trunionosis
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of the study is to develop a biomarker assay to be used as a diagnostic tool for adverse local tissue reaction, or tissue necrosis, in a metal on metal total hip replacement.
A convenience sample of a total of 100 hip patients will be enrolled: 50 metal-on-metal revision hips, 25 metal-on-poly revision hips, and 25 pre-operative total hips (no implant, control group) will be enrolled. Preoperative blood serum samples and intraoperative synovial fluid will be obtained from all hips and used for biomarker testing. Additionally, intraoperative assessment of tissue necrosis will be assessed.
Read the detailed description
Well-functioning MoM implants have shown an increase in serum cobalt and chromium (CoCr) ion levels from the metal debris generated from the implant wear.However, the current evidence suggests that measuring ion levels is unreliable and that increasing ion levels do not correlate with tissue damage. In addition to measuring blood and synovial fluid metal ion levels, ultrasound and MRI with metal artifact reduction sequences (MARS) have been utilized to assess periarticular reactions secondary to metal wear debris. Despite metal reduction software these scans are frequently difficult to interpret. While each of these tests has merit, at the present time there is no single diagnostic test available which delineates the key issue that demands urgent surgical intervention, i.e. tissue necrosis. It is important to have a reliable test to guide surgeons and patients in the shared decision-making process of when surgical intervention is necessary to prevent disabling tissue damage. For this reason, the current study proposes an examination of preoperative serum samples of subjects in addition to synovial fluid collected during revision surgery for biomarkers that may indicate tissue necrosis. To maximize the chance of success of identifying serum biomarkers, all samples will be analyzed using multianalyte assay, biomarker tests. The purpose of the study is to develop a biomarker assay to be used as a diagnostic tool for adverse local tissue reaction, or tissue necrosis, in a metal on metal total hip replacement.
A convenience sample of a total of 100 hip patients will be enrolled: 50 metal-on-metal revision hips, 25 metal-on-poly revision hips, and 25 pre-operative total hips (no implant, control group) will be enrolled. Preoperative blood serum samples and intraoperative synovial fluid will be obtained from all hips and used for biomarker testing. Additionally, intraoperative assessment of tissue necrosis will be assessed.
- Conditions
- Arthritis, Failure of Total Hip
- Keywords
- tissue necrosis, metal on metal total hip, biomarker
- Medical subject headings
- Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Control | pre-operative total hip patients with no existing total hip implant | |
| Metal on polyethylene | patients who have a failed metal on polyethylene total hip implant and are presenting for revision surgery | |
| Metal on Metal | patients who have a failed metal on metal total hip implant and are presenting for revision surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of patients with serum and synovial fluid biomarkers
Blood Serum and Synovial fluid will be tested using a multi-analyte assay test
Measured: participants will be followed for the duration of their hospital stay, an expected average of 2 hours
Secondary outcomes (1)
The number of patients with tissue necrosis
Tissue necrosis will be assessed during total hip surgery.
Tissue necrosis will be scored in subsets including: intraoperative tissue damage, histological necrosis score, histologic ALVAL score, inflammatory infiltrate, and tissue organization
Measured: participants will be followed for the duration of their hospital stay, an expected average of 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2014 (estimated)
- Study start4 Aug 2014
- Primary completion17 May 2018
- Study completion12 Aug 2020
Why it stopped: The lab contracted by the site to complete specimen analysis backed out on their agreement to do so. At this time it is not feasible for a new contract to be entered into by the site.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Arthritis, Failure of Total HipStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 174 participants (actual)
Sponsor and investigators
- Lead sponsor
- OrthoCarolina Research Institute, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Charlotte Orthopedic Hospital
- Responsible party
- Sponsor
- Investigators
- Thomas Fehring, MD, Principal investigator, OrthoCarolina Research Institute, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02208271
- Sponsor's protocol ID
- HK003-14014
- Status last verified
- May 2026
- First submitted
- 17 Jul 2014
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
MacDonald SJ. Metal-on-metal total hip arthroplasty: the concerns. Clin Orthop Relat Res. 2004 Dec;(429):86-93. doi: 10.1097/01.blo.0000150309.48474.8b.
PubMed 15577471Lindgren JU, Brismar BH, Wikstrom AC. Adverse reaction to metal release from a modular metal-on-polyethylene hip prosthesis. J Bone Joint Surg Br. 2011 Oct;93(10):1427-30. doi: 10.1302/0301-620X.93B10.27645.
PubMed 21969447Lombardi AV Jr, Barrack RL, Berend KR, Cuckler JM, Jacobs JJ, Mont MA, Schmalzried TP. The Hip Society: algorithmic approach to diagnosis and management of metal-on-metal arthroplasty. J Bone Joint Surg Br. 2012 Nov;94(11 Suppl A):14-8. doi: 10.1302/0301-620X.94B11.30680.
PubMed 23118373Cobb AG, Schmalzreid TP. The clinical significance of metal ion release from cobalt-chromium metal-on-metal hip joint arthroplasty. Proc Inst Mech Eng H. 2006 Feb;220(2):385-98. doi: 10.1243/09544119JEIM78.
PubMed 16669404Mabilleau G, Kwon YM, Pandit H, Murray DW, Sabokbar A. Metal-on-metal hip resurfacing arthroplasty: a review of periprosthetic biological reactions. Acta Orthop. 2008 Dec;79(6):734-47. doi: 10.1080/17453670810016795.
PubMed 19085489Tower SS. Arthroprosthetic cobaltism: neurological and cardiac manifestations in two patients with metal-on-metal arthroplasty: a case report. J Bone Joint Surg Am. 2010 Dec 1;92(17):2847-51. doi: 10.2106/JBJS.J.00125. Epub 2010 Oct 29. No abstract available.
PubMed 21037026Campbell P, Ebramzadeh E, Nelson S, Takamura K, De Smet K, Amstutz HC. Histological features of pseudotumor-like tissues from metal-on-metal hips. Clin Orthop Relat Res. 2010 Sep;468(9):2321-7. doi: 10.1007/s11999-010-1372-y.
PubMed 20458645Leopold SS, Berger RA, Patterson L, Skipor AK, Urban RM, Jacobs JJ. Serum titanium level for diagnosis of a failed, metal-backed patellar component. J Arthroplasty. 2000 Oct;15(7):938-43. doi: 10.1054/arth.2000.6632.
PubMed 11061457Griffin WL, Fehring TK, Kudrna JC, Schmidt RH, Christie MJ, Odum SM, Dennos AC. Are metal ion levels a useful trigger for surgical intervention? J Arthroplasty. 2012 Sep;27(8 Suppl):32-6. doi: 10.1016/j.arth.2012.03.020. Epub 2012 May 17.
PubMed 22608683
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Validated Necrosis Assay to Determine the Need for Revision Surgery in Metal-on-metal Total Hip Arthroplasty
- ClinicalTrials.gov ID
- NCT02208271
- Acronym / sponsor ID
- HK003-14014
- Conditions
- Arthritis, Failure of Total Hip
- Keywords
- tissue necrosis, metal on metal total hip, biomarker
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: The lab contracted by the site to complete specimen analysis backed out on their agreement to do so. At this time it is not feasible for a new contract to be entered into by the site.
- Enrolment
- 174 participants (actual)
- Lead sponsor
- OrthoCarolina Research Institute, Inc.University, hospital or other
- Collaborators
- Charlotte Orthopedic Hospital
- Study start
- 4 Aug 2014 (actual)
- Primary completion
- 17 May 2018 (actual)
- Study completion
- 12 Aug 2020 (actual)
- First posted
- 5 Aug 2014 (estimated)
- Results
- Not posted in the source record
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 the study is to develop a biomarker assay to be used as a diagnostic tool for adverse local tissue reaction, or tissue necrosis, in a metal on metal total hip replacement.
A convenience sample of a total of 100 hip patients will be enrolled: 50 metal-on-metal revision hips, 25 metal-on-poly revision hips, and 25 pre-operative total hips (no implant, control group) will be enrolled. Preoperative blood serum samples and intraoperative synovial fluid will be obtained from all hips and used for biomarker testing. Additionally, intraoperative assessment of tissue necrosis will be assessed.
Detailed description
Well-functioning MoM implants have shown an increase in serum cobalt and chromium (CoCr) ion levels from the metal debris generated from the implant wear.However, the current evidence suggests that measuring ion levels is unreliable and that increasing ion levels do not correlate with tissue damage. In addition to measuring blood and synovial fluid metal ion levels, ultrasound and MRI with metal artifact reduction sequences (MARS) have been utilized to assess periarticular reactions secondary to metal wear debris. Despite metal reduction software these scans are frequently difficult to interpret. While each of these tests has merit, at the present time there is no single diagnostic test available which delineates the key issue that demands urgent surgical intervention, i.e. tissue necrosis. It is important to have a reliable test to guide surgeons and patients in the shared decision-making process of when surgical intervention is necessary to prevent disabling tissue damage. For this reason, the current study proposes an examination of preoperative serum samples of subjects in addition to synovial fluid collected during revision surgery for biomarkers that may indicate tissue necrosis. To maximize the chance of success of identifying serum biomarkers, all samples will be analyzed using multianalyte assay, biomarker tests. The purpose of the study is to develop a biomarker assay to be used as a diagnostic tool for adverse local tissue reaction, or tissue necrosis, in a metal on metal total hip replacement.
A convenience sample of a total of 100 hip patients will be enrolled: 50 metal-on-metal revision hips, 25 metal-on-poly revision hips, and 25 pre-operative total hips (no implant, control group) will be enrolled. Preoperative blood serum samples and intraoperative synovial fluid will be obtained from all hips and used for biomarker testing. Additionally, intraoperative assessment of tissue necrosis will be assessed.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | – | –pre-operative total hip patients with no existing total hip implant |
| Metal on polyethylene | – | –patients who have a failed metal on polyethylene total hip implant and are presenting for revision surgery |
| Metal on Metal | – | –patients who have a failed metal on metal total hip implant and are presenting for revision surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A convenience sample of a total of 100 hip patients will be enrolled at orthopedic clinics.
Key inclusion criteria (5 listed)
- Patients presenting for a metal on metal hip revision who have cobalt and chromium metal ion levels tested within 6 months of the date of the planned revision surgery.
- Patients presenting for a metal on poly hip revision
- Revision hip patients must be greater than one year postoperative
- The diagnosis at the time of the index, or primary, hip replacement was osteoarthritis.
- Patients who have hip osteoarthritis but have not had a total hip surgery (control)
Key exclusion criteria (10 listed)
- Patients presenting for a metal on metal hip revision who have cobalt and chromium metal ion levels tested >6 months of the date of the planned revision
- Patients with a total hip on the contralateral side.
- Patients with a prior history of periprosthetic infection
- Revision cases where the diagnosis at the time of the index, or primary, hip replacement was not osteoarthritis.
- Prisoners
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The number of patients with serum and synovial fluid biomarkers
Time frame: participants will be followed for the duration of their hospital stay, an expected average of 2 hours
Blood Serum and Synovial fluid will be tested using a multi-analyte assay test
1 secondary outcome
The number of patients with tissue necrosis
Time frame: participants will be followed for the duration of their hospital stay, an expected average of 2 hours
Results and safety
The study was stopped early (reason given: The lab contracted by the site to complete specimen analysis backed out on their agreement to do so. At this time it is not feasible for a new contract to be entered into by the site.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Background: PubMed 15577471MacDonald SJ. Metal-on-metal total hip arthroplasty: the concerns. Clin Orthop Relat Res. 2004 Dec;(429):86-93. doi: 10.1097/01.blo.0000150309.48474.8b.
- Background: PubMed 21969447Lindgren JU, Brismar BH, Wikstrom AC. Adverse reaction to metal release from a modular metal-on-polyethylene hip prosthesis. J Bone Joint Surg Br. 2011 Oct;93(10):1427-30. doi: 10.1302/0301-620X.93B10.27645.
- Background: PubMed 23118373Lombardi AV Jr, Barrack RL, Berend KR, Cuckler JM, Jacobs JJ, Mont MA, Schmalzried TP. The Hip Society: algorithmic approach to diagnosis and management of metal-on-metal arthroplasty. J Bone Joint Surg Br. 2012 Nov;94(11 Suppl A):14-8. doi: 10.1302/0301-620X.94B11.30680.
- Background: PubMed 16669404Cobb AG, Schmalzreid TP. The clinical significance of metal ion release from cobalt-chromium metal-on-metal hip joint arthroplasty. Proc Inst Mech Eng H. 2006 Feb;220(2):385-98. doi: 10.1243/09544119JEIM78.
- Background: PubMed 19085489Mabilleau G, Kwon YM, Pandit H, Murray DW, Sabokbar A. Metal-on-metal hip resurfacing arthroplasty: a review of periprosthetic biological reactions. Acta Orthop. 2008 Dec;79(6):734-47. doi: 10.1080/17453670810016795.
- Background: PubMed 21037026Tower SS. Arthroprosthetic cobaltism: neurological and cardiac manifestations in two patients with metal-on-metal arthroplasty: a case report. J Bone Joint Surg Am. 2010 Dec 1;92(17):2847-51. doi: 10.2106/JBJS.J.00125. Epub 2010 Oct 29. No abstract available.
- Background: PubMed 20458645Campbell P, Ebramzadeh E, Nelson S, Takamura K, De Smet K, Amstutz HC. Histological features of pseudotumor-like tissues from metal-on-metal hips. Clin Orthop Relat Res. 2010 Sep;468(9):2321-7. doi: 10.1007/s11999-010-1372-y.
- Background: PubMed 11061457Leopold SS, Berger RA, Patterson L, Skipor AK, Urban RM, Jacobs JJ. Serum titanium level for diagnosis of a failed, metal-backed patellar component. J Arthroplasty. 2000 Oct;15(7):938-43. doi: 10.1054/arth.2000.6632.
- Background: PubMed 22608683Griffin WL, Fehring TK, Kudrna JC, Schmidt RH, Christie MJ, Odum SM, Dennos AC. Are metal ion levels a useful trigger for surgical intervention? J Arthroplasty. 2012 Sep;27(8 Suppl):32-6. doi: 10.1016/j.arth.2012.03.020. Epub 2012 May 17.
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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.
Thomas Fehring, MD principal investigator
OrthoCarolina Research Institute, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Arthritis, Failure of Total Hip, run by OrthoCarolina Research Institute, Inc. 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 5 inclusion and 10 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 22 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?
The study was stopped early (reason given: The lab contracted by the site to complete specimen analysis backed out on their agreement to do so. At this time it is not feasible for a new contract to be entered into by the site.). Results are not available in the source record.
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?
The number of patients with serum and synovial fluid biomarkers (time frame: participants will be followed for the duration of their hospital stay, an expected average of 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02208271, which also lists 9 linked publications.
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 22 May 2026.