Prosthetic Joint InfectionDECISIONNCT04858217
Periprosthetic Joint Infections: Diagnostic Accuracy and Cost-effectiveness Analysis of Serum and Synovial Markers
An observational study of Prosthetic Joint Infection, run by Istituto Ortopedico Rizzoli at 1 site in Italy.
Trial summary
Total joint replacement (TJR) is an increasing effective procedure in orthopedics. However, TJR failure due to aseptic or septic loosening remains an important problem, often due to predisposing factors of the patient, which determine the need to perform a revision surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prosthetic Joint Infection
- How many people
- 270 participants
- Where
- 1 siteItaly
- Study dates
- 1 Feb 2022to 31 Mar 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 maximum number of n = 270 patients who will have to undergo hip or knee prosthetic revision surgery will be enrolled, of which n = 54 for late infection ascertained by previous microbiological analyzes, and n = 216 for prosthetic failure not from infection. Patients will be enrolled in the clinical study only after having signed and dated personally or by the patient's legal representative, the written informed consent. Therefore, enrollment in the study (exclusively of a diagnostic type) will not in any case influence the established diagnostic and therapeutic path.
Who may be able to join
- Patients requiring hip or knee replacement surgery: i) for 'late' joint prosthesis infection, present for at least 90 days from the date of the arthroplasty (first surgical phase); II) for non-infectious causes (mobilization, wear, instability, misalignment, adverse reactions to local tissues or other aseptic causes), also present for at least 90 days, and which have not had other re-operations on the same joint, and which will be a one-step review;
- Previous clinical data and laboratory and radiological examinations available.
Who cannot join
- Patients affected by 'early' joint prosthesis infection, with clinical symptom latency of less than 90 days (in this specific subset of patients there is in fact still considerable heterogeneity and little consensus about the diagnostic levels of white blood cell count and percentage of neutrophils).
- Patients suffering from joint prosthesis infection involving joints other than the hip or knee.
- Severe cognitive impairment or psychiatric disorders;
- Pregnant women.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Istituto Ortopedico Rizzoli
Bologna, 40134
Gianluca Giavaresi, MD, +393774548728, gianluca.giavaresi@ior.it
About this study
Official title: Diagnostic Accuracy and Cost-effectiveness Analysis of Serum and Synovial Fluid Markers for the Diagnosis of Periprosthetic Hip and Knee Joint Infections
Total joint replacement (TJR) is an increasing effective procedure in orthopedics. However, TJR failure due to aseptic or septic loosening remains an important problem, often due to predisposing factors of the patient, which determine the need to perform a revision surgery. In light of the recent conclusions emerged on the still open problems concerning the diagnostic accuracy of serum and synovial fluid markers in the diagnosis of peri-prosthetic joint infection (PJI), the project aims at evaluating the diagnostic accuracy and cost-effectiveness of the combination of serum and/or synovial markers in the diagnosis of PJI. Through a diagnostic clinical study on patients hospitalized for revision surgery the project would provide evidences on the potentiality of the combination of some markers in accelerating the PJI diagnosis for the best selection of surgical strategy, choosing the suitable cutoff thresholds to mitigate the effect of some factors on markers' discriminatory capability.
Read the detailed description
Total joint arthroplasties (TJA) are constantly increasing in older and multi-morbid patients; knee and hip joints are the most frequently treated due to high incidence of osteoarthritis in these joints. The indication to TJA is now extended to younger and active patients with high functional demands and longer life expectancy. Because of these, an increase in revision surgeries and a PJI risk is also expected. The type of revision surgery (RS) approach and of antimicrobial treatments is based on the presence or absence of infection: one-stage revision with maintenance/replacement of prosthesis in combination with debridement and irrigation (aseptic RS); and two-stage revision with prosthesis removal, debridement and irrigation, the possible use of a temporary spacer, and the potential reimplantation after weeks or months (septic RS).
Today, PJI remains an important dangerous and devastating complication; it has been reported for hip and knee joints an incidence of 0.2-1.5%, prosthesis failure of 15-25%, revision success rate of 80-95% and annual cost per infection of $20,000-$40,000. The timely and most accurate diagnosis is essential for the correct treatment of PJI as patients undergoing revision need extensive physical, psychological and economic supports. Following the definition and standardization of diagnostic major and minor criteria for PJI by the Musculoskeletal Infection Society (MSIS) an improvement in the diagnosis and treatment of PJI was observed. Recently, the International Consensus Group on PJI revised MSIS criteria defining that patients should be considered to have PJI in the presence of one of the major criteria or three of five minor criteria. Finally, an evidence-based and validated criteria for hip and knee PJI definition to diagnose patients within the preoperative period was published in 2018. Patients with an aggregate score of more than or equal to 6 are considered infected, while a 2-5 score requires the inclusion of intraoperative findings (positive histology, purulence and single positive culture) for confirming or refuting the diagnosis. A 4-5 score is inconclusive, and a score of less than or equal to 3 is not infected.
During the last International Consensus Meeting on Musculoskeletal Infection, various questions on PJI were discussed and among them the working groups (WG) provided recommendations based on limited (4 - due to small numbers) and moderate (12 and 19) levels of evidence: WG4, on which patient-specific factors influence the thresholds for serum and synovial markers in acute and chronic PJI; WG12, on which serum tests have the best diagnostic accuracy for PJI and if the combination of any number of tests increase the diagnostic accuracy; WG19, if the profile of organisms causing surgical site infection or PJI following orthopaedic procedures changed over recent years. The WG4 highlighted that no inflammatory arthritis (IA)-specific factors are known to influence the thresholds for serum and synovial markers in PJIs. It appears that in IA patients there are overlaps in values of synovial markers such as alphadefensin, white blood cell count (sWBC) and C-reactive protein (CRP), limiting their usefulness in differentiating septic from aseptic patients. The WG12 stated that it is evident that diagnosis of PJI cannot be based solely on serological tests and that CRP and erythrocyte sedimentation rate (ESR) are well-researched screening tests and have high sensitivity when used alone. However, the combination of serological tests has shown to improve diagnostic accuracy, but the identification of the optimal combination needs further investigations. Finally, the WG19 recommended to perform further investigations regarding the profile of microorganism with next generation sequencing (NGS), as it may confer significant antibiotic selection implications.
Among pre-operative test on synovial fluid, alpha-defensin showed the highest degree of accuracy in the diagnosis of PJI when measured by laboratory-based immunoassay rather than lateral flow test, suggesting that care must be taken with interpretation of the lateral flow test when relying on its results for the intra-operative diagnosis. Synovial fluid could be tested for other newly markers such calprotectin and cathelicidin LL-37, whose sensitivity and specifity are to be defined or for microbiological tests.
Synovial fluid analysis for WBC and %PMN has high sensitivity and specificity in diagnosing PJI, and it represents an easy and widespread available method. Our meta-analysis evaluated: 1) accuracy in terms of sensitivity and specificity of synovial fluid WBC and %PMN tests in the diagnosis of PJI after total knee (TKA) and hip (THA) arthroplasty; 2) which test yielded superior test performance; and 3) the influence of study characteristics such as anatomic site and threshold value on the diagnostic accuracy of these tests. The meta-analysis results revealed that both synovial fluid WBC and %PMN have a high specificity and sensitivity in detecting PJI, and no clear superiority of one test over the other exists. In addition, an anatomic site effect was demonstrated on sensitivity of synovial fluid %PMN, suggesting that cutoff thresholds should be identified separately for TKA and THA. The differences in bearing surfaces and the possibility of fretting corrosion in dual taper stem designs might substantially alter automated synovial fluid analysis in THA compared to TKA.
The aim of the project is to evaluate the diagnostic accuracy and cost-effectiveness of the combination of serum and/or synovial markers in the pre- or intraoperative (lateral flow test)/post- diagnosis of PJI. To such purpose a clinical diagnostic study on patients hospitalized for revision surgery based on the guidelines of MSIS will be carried out; the combinations of two or more markers with the highest diagnostic accuracies will be identified and evaluated in term of cost-effectiveness towards individual markers whose thresholds are based on the MSIS 2013 ICM. The significance of this research is to provide evidences on the potentiality of the combination of some markers in accelerating the PJI diagnosis for the best selection of surgical strategy to be followed. A prompt diagnosis and recognition of the etiological agent are crucial to define the appropriate antimicrobial therapy and to reduce to a minimum the cases of erroneous diagnosis and of consequent erroneous surgical conduct, with the need for subsequent re-operations, and multiplication of risk for patients and of costs for the health care system.
- Conditions
- Prosthetic Joint Infection
- Keywords
- prosthetic joint infection, biomarker, synovial fluid, serum
What is being measured
The primary outcome is the main question the study is designed to answer.
White blood cell count (WBC, cells/μL)
Measured: 7 days
Erythrocyte sedimentation rate (ESR, mm/hour)
Measured: 7 days
C-reactive Protein (CRP, mg/L)
Measured: 7 days
D-dimer (ng/ml)
Measured: 7 days
IL-6 (pg/ml)
Measured: 7 days
Procalcitonin (ng/ml)
Measured: 2 months
Soluble Intercellular Adhesion Molecule-1 (sICAM-1, ng/L)
Measured: 7 days
Synovial WBC (sWBC, cells/μL)
Measured: 7 days
Percentage of polymorphonucleates (%PMM, %) in synovial fluid
Measured: 7 days
Synovial C-reactive Protein (sCRP, mg/L)
Measured: 7 days
Synovial alpha-defensin (positive or negative)
Measured: 7 days
Synovial leukocyte esterase (positive or negative)
Measured: 7 days
Synovial IL-6 (pg/ml)
Measured: 7 days
Synovial cathelicidin LL-37 (μg/ml)
Measured: 7 days
Synovial calprotectin (ng/ml)
Measured: 7 days
Secondary outcomes (3)
Serum and synovial biomarkers cut-off for prosthetic joint infections
Test various cut-off values for selected serum and synovial biomarkers for diagnosing PJI.
Measured: 2 months
Assessment of antimicrobial resistances of isolated microrganisms
Bacterial gene sequencing to indentify antimicrobial resistance by Ion AmpliSeqTM Antimicrobial Resistance (AMR) Research Panel.
Measured: 2 months
Assessment of biofilm formation capability of isolated microrganisms
Measure the level of cyclic dimeric bis- (3'-5 ') - guanosine monophosphate (c-di-GMP) which influences biofilm formation by proteomic analysis (MALDI-TOF).
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2021
- Study start1 Feb 2022
- Primary completion17 Jun 2025
- Study completion31 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Prosthetic Joint InfectionStudies of the same condition, open and under way.
- More trials run by Istituto Ortopedico RizzoliThe sponsor's other registered studies.
- 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Ortopedico Rizzoli
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Responsible party
- Sponsor
- Investigators
- Gianluca Giavaresi, MD, Principal investigator, Istituto Ortopedico Rizzoli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04858217
- Sponsor's protocol ID
- 37/2021/Sper/IOR
- Acronym
- DECISION
- Status last verified
- Sep 2025
- First submitted
- 8 Apr 2021
- Last updated
- 22 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pabinger C, Geissler A. Utilization rates of hip arthroplasty in OECD countries. Osteoarthritis Cartilage. 2014 Jun;22(6):734-41. doi: 10.1016/j.joca.2014.04.009. Epub 2014 Apr 26.
PubMed 24780823Pabinger C, Lothaller H, Geissler A. Utilization rates of knee-arthroplasty in OECD countries. Osteoarthritis Cartilage. 2015 Oct;23(10):1664-73. doi: 10.1016/j.joca.2015.05.008. Epub 2015 May 29.
PubMed 26028142Brochin RL, Phan K, Poeran J, Zubizarreta N, Galatz LM, Moucha CS. Trends in Periprosthetic Hip Infection and Associated Costs: A Population-Based Study Assessing the Impact of Hospital Factors Using National Data. J Arthroplasty. 2018 Jul;33(7S):S233-S238. doi: 10.1016/j.arth.2018.02.062. Epub 2018 Feb 22.
PubMed 29573912Schwarz EM, Parvizi J, Gehrke T, Aiyer A, Battenberg A, Brown SA, Callaghan JJ, Citak M, Egol K, Garrigues GE, Ghert M, Goswami K, Green A, Hammound S, Kates SL, McLaren AC, Mont MA, Namdari S, Obremskey WT, O'Toole R, Raikin S, Restrepo C, Ricciardi B, Saeed K, Sanchez-Sotelo J, Shohat N, Tan T, Thirukumaran CP, Winters B. 2018 International Consensus Meeting on Musculoskeletal Infection: Research Priorities from the General Assembly Questions. J Orthop Res. 2019 May;37(5):997-1006. doi: 10.1002/jor.24293. Epub 2019 Apr 25.
PubMed 30977537Bonanzinga T, Ferrari MC, Tanzi G, Vandenbulcke F, Zahar A, Marcacci M. The role of alpha defensin in prosthetic joint infection (PJI) diagnosis: a literature review. EFORT Open Rev. 2019 Jan 23;4(1):10-13. doi: 10.1302/2058-5241.4.180029. eCollection 2019 Jan.
PubMed 30800475Kunutsor SK, Beswick AD, Peters TJ, Gooberman-Hill R, Whitehouse MR, Blom AW, Moore AJ. Health Care Needs and Support for Patients Undergoing Treatment for Prosthetic Joint Infection following Hip or Knee Arthroplasty: A Systematic Review. PLoS One. 2017 Jan 3;12(1):e0169068. doi: 10.1371/journal.pone.0169068. eCollection 2017.
PubMed 28046049Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, Rao N, Hanssen A, Wilson WR; Infectious Diseases Society of America. Executive summary: diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013 Jan;56(1):1-10. doi: 10.1093/cid/cis966.
PubMed 23230301Parvizi J, Zmistowski B, Berbari EF, Bauer TW, Springer BD, Della Valle CJ, Garvin KL, Mont MA, Wongworawat MD, Zalavras CG. New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011 Nov;469(11):2992-4. doi: 10.1007/s11999-011-2102-9. No abstract available.
PubMed 21938532Cats-Baril W, Gehrke T, Huff K, Kendoff D, Maltenfort M, Parvizi J. International consensus on periprosthetic joint infection: description of the consensus process. Clin Orthop Relat Res. 2013 Dec;471(12):4065-75. doi: 10.1007/s11999-013-3329-4. Epub 2013 Oct 24. No abstract available.
PubMed 24155178Parvizi J, Tan TL, Goswami K, Higuera C, Della Valle C, Chen AF, Shohat N. The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria. J Arthroplasty. 2018 May;33(5):1309-1314.e2. doi: 10.1016/j.arth.2018.02.078. Epub 2018 Feb 26.
PubMed 29551303Han X, Xie K, Jiang X, Wang L, Wu H, Qu X, Yan M. Synovial fluid alpha-defensin in the diagnosis of periprosthetic joint infection: the lateral flow test is an effective intraoperative detection method. J Orthop Surg Res. 2019 Aug 28;14(1):274. doi: 10.1186/s13018-019-1320-9.
PubMed 31455372Marson BA, Deshmukh SR, Grindlay DJC, Scammell BE. Alpha-defensin and the Synovasure lateral flow device for the diagnosis of prosthetic joint infection: a systematic review and meta-analysis. Bone Joint J. 2018 Jun 1;100-B(6):703-711. doi: 10.1302/0301-620X.100B6.BJJ-2017-1563.R1.
PubMed 29855233Suen K, Keeka M, Ailabouni R, Tran P. Synovasure 'quick test' is not as accurate as the laboratory-based alpha-defensin immunoassay: a systematic review and meta-analysis. Bone Joint J. 2018 Jan;100-B(1):66-72. doi: 10.1302/0301-620X.100B1.BJJ-2017-0630.R1.
PubMed 29305453Wouthuyzen-Bakker M, Ploegmakers JJW, Ottink K, Kampinga GA, Wagenmakers-Huizenga L, Jutte PC, Kobold ACM. Synovial Calprotectin: An Inexpensive Biomarker to Exclude a Chronic Prosthetic Joint Infection. J Arthroplasty. 2018 Apr;33(4):1149-1153. doi: 10.1016/j.arth.2017.11.006. Epub 2017 Nov 13.
PubMed 29224989Alvand A, Rezapoor M, Parvizi J. The Role of Biomarkers for the Diagnosis of Implant-Related Infections in Orthopaedics and Trauma. Adv Exp Med Biol. 2017;971:69-79. doi: 10.1007/5584_2017_11.
PubMed 28243953
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnostic Accuracy and Cost-effectiveness Analysis of Serum and Synovial Fluid Markers for the Diagnosis of Periprosthetic Hip and Knee Joint Infections
- ClinicalTrials.gov ID
- NCT04858217
- Acronym / sponsor ID
- DECISION / 37/2021/Sper/IOR
- Conditions
- Prosthetic Joint Infection
- Keywords
- prosthetic joint infection, biomarker, synovial fluid, serum
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- Istituto Ortopedico RizzoliUniversity, hospital or other
- Collaborators
- IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 17 Jun 2025 (actual)
- Study completion
- 31 Mar 2026 (estimated)
- First posted
- 26 Apr 2021 (actual)
- 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.
Total joint replacement (TJR) is an increasing effective procedure in orthopedics. However, TJR failure due to aseptic or septic loosening remains an important problem, often due to predisposing factors of the patient, which determine the need to perform a revision surgery. In light of the recent conclusions emerged on the still open problems concerning the diagnostic accuracy of serum and synovial fluid markers in the diagnosis of peri-prosthetic joint infection (PJI), the project aims at evaluating the diagnostic accuracy and cost-effectiveness of the combination of serum and/or synovial markers in the diagnosis of PJI. Through a diagnostic clinical study on patients hospitalized for revision surgery the project would provide evidences on the potentiality of the combination of some markers in accelerating the PJI diagnosis for the best selection of surgical strategy, choosing the suitable cutoff thresholds to mitigate the effect of some factors on markers' discriminatory capability.
Detailed description
Total joint arthroplasties (TJA) are constantly increasing in older and multi-morbid patients; knee and hip joints are the most frequently treated due to high incidence of osteoarthritis in these joints. The indication to TJA is now extended to younger and active patients with high functional demands and longer life expectancy. Because of these, an increase in revision surgeries and a PJI risk is also expected. The type of revision surgery (RS) approach and of antimicrobial treatments is based on the presence or absence of infection: one-stage revision with maintenance/replacement of prosthesis in combination with debridement and irrigation (aseptic RS); and two-stage revision with prosthesis removal, debridement and irrigation, the possible use of a temporary spacer, and the potential reimplantation after weeks or months (septic RS).
Today, PJI remains an important dangerous and devastating complication; it has been reported for hip and knee joints an incidence of 0.2-1.5%, prosthesis failure of 15-25%, revision success rate of 80-95% and annual cost per infection of $20,000-$40,000. The timely and most accurate diagnosis is essential for the correct treatment of PJI as patients undergoing revision need extensive physical, psychological and economic supports. Following the definition and standardization of diagnostic major and minor criteria for PJI by the Musculoskeletal Infection Society (MSIS) an improvement in the diagnosis and treatment of PJI was observed. Recently, the International Consensus Group on PJI revised MSIS criteria defining that patients should be considered to have PJI in the presence of one of the major criteria or three of five minor criteria. Finally, an evidence-based and validated criteria for hip and knee PJI definition to diagnose patients within the preoperative period was published in 2018. Patients with an aggregate score of more than or equal to 6 are considered infected, while a 2-5 score requires the inclusion of intraoperative findings (positive histology, purulence and single positive culture) for confirming or refuting the diagnosis. A 4-5 score is inconclusive, and a score of less than or equal to 3 is not infected.
During the last International Consensus Meeting on Musculoskeletal Infection, various questions on PJI were discussed and among them the working groups (WG) provided recommendations based on limited (4 - due to small numbers) and moderate (12 and 19) levels of evidence: WG4, on which patient-specific factors influence the thresholds for serum and synovial markers in acute and chronic PJI; WG12, on which serum tests have the best diagnostic accuracy for PJI and if the combination of any number of tests increase the diagnostic accuracy; WG19, if the profile of organisms causing surgical site infection or PJI following orthopaedic procedures changed over recent years. The WG4 highlighted that no inflammatory arthritis (IA)-specific factors are known to influence the thresholds for serum and synovial markers in PJIs. It appears that in IA patients there are overlaps in values of synovial markers such as alphadefensin, white blood cell count (sWBC) and C-reactive protein (CRP), limiting their usefulness in differentiating septic from aseptic patients. The WG12 stated that it is evident that diagnosis of PJI cannot be based solely on serological tests and that CRP and erythrocyte sedimentation rate (ESR) are well-researched screening tests and have high sensitivity when used alone. However, the combination of serological tests has shown to improve diagnostic accuracy, but the identification of the optimal combination needs further investigations. Finally, the WG19 recommended to perform further investigations regarding the profile of microorganism with next generation sequencing (NGS), as it may confer significant antibiotic selection implications.
Among pre-operative test on synovial fluid, alpha-defensin showed the highest degree of accuracy in the diagnosis of PJI when measured by laboratory-based immunoassay rather than lateral flow test, suggesting that care must be taken with interpretation of the lateral flow test when relying on its results for the intra-operative diagnosis. Synovial fluid could be tested for other newly markers such calprotectin and cathelicidin LL-37, whose sensitivity and specifity are to be defined or for microbiological tests.
Synovial fluid analysis for WBC and %PMN has high sensitivity and specificity in diagnosing PJI, and it represents an easy and widespread available method. Our meta-analysis evaluated: 1) accuracy in terms of sensitivity and specificity of synovial fluid WBC and %PMN tests in the diagnosis of PJI after total knee (TKA) and hip (THA) arthroplasty; 2) which test yielded superior test performance; and 3) the influence of study characteristics such as anatomic site and threshold value on the diagnostic accuracy of these tests. The meta-analysis results revealed that both synovial fluid WBC and %PMN have a high specificity and sensitivity in detecting PJI, and no clear superiority of one test over the other exists. In addition, an anatomic site effect was demonstrated on sensitivity of synovial fluid %PMN, suggesting that cutoff thresholds should be identified separately for TKA and THA. The differences in bearing surfaces and the possibility of fretting corrosion in dual taper stem designs might substantially alter automated synovial fluid analysis in THA compared to TKA.
The aim of the project is to evaluate the diagnostic accuracy and cost-effectiveness of the combination of serum and/or synovial markers in the pre- or intraoperative (lateral flow test)/post- diagnosis of PJI. To such purpose a clinical diagnostic study on patients hospitalized for revision surgery based on the guidelines of MSIS will be carried out; the combinations of two or more markers with the highest diagnostic accuracies will be identified and evaluated in term of cost-effectiveness towards individual markers whose thresholds are based on the MSIS 2013 ICM. The significance of this research is to provide evidences on the potentiality of the combination of some markers in accelerating the PJI diagnosis for the best selection of surgical strategy to be followed. A prompt diagnosis and recognition of the etiological agent are crucial to define the appropriate antimicrobial therapy and to reduce to a minimum the cases of erroneous diagnosis and of consequent erroneous surgical conduct, with the need for subsequent re-operations, and multiplication of risk for patients and of costs for the health care system.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A maximum number of n = 270 patients who will have to undergo hip or knee prosthetic revision surgery will be enrolled, of which n = 54 for late infection ascertained by previous microbiological analyzes, and n = 216 for prosthetic failure not from infection. Patients will be enrolled in the clinical study only after having signed and dated personally or by the patient's legal representative, the written informed consent. Therefore, enrollment in the study (exclusively of a diagnostic type) will not in any case influence the established diagnostic and therapeutic path.
Key inclusion criteria (2 listed)
- Patients requiring hip or knee replacement surgery: i) for 'late' joint prosthesis infection, present for at least 90 days from the date of the arthroplasty (first surgical phase); II) for non-infectious causes (mobilization, wear, instability, misalignment, adverse reactions to local tissues or other aseptic causes), also present for at least 90 days, and which have not had other re-operations on the same joint, and which will be a one-step review;
- Previous clinical data and laboratory and radiological examinations available.
Key exclusion criteria (4 listed)
- Patients affected by 'early' joint prosthesis infection, with clinical symptom latency of less than 90 days (in this specific subset of patients there is in fact still considerable heterogeneity and little consensus about the diagnostic levels of white blood cell count and percentage of neutrophils).
- Patients suffering from joint prosthesis infection involving joints other than the hip or knee.
- Severe cognitive impairment or psychiatric disorders;
- Pregnant women.
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
White blood cell count (WBC, cells/μL)
Time frame: 7 days
Erythrocyte sedimentation rate (ESR, mm/hour)
Time frame: 7 days
C-reactive Protein (CRP, mg/L)
Time frame: 7 days
D-dimer (ng/ml)
Time frame: 7 days
IL-6 (pg/ml)
Time frame: 7 days
Procalcitonin (ng/ml)
Time frame: 2 months
Soluble Intercellular Adhesion Molecule-1 (sICAM-1, ng/L)
Time frame: 7 days
Synovial WBC (sWBC, cells/μL)
Time frame: 7 days
Percentage of polymorphonucleates (%PMM, %) in synovial fluid
Time frame: 7 days
Synovial C-reactive Protein (sCRP, mg/L)
Time frame: 7 days
Synovial alpha-defensin (positive or negative)
Time frame: 7 days
Synovial leukocyte esterase (positive or negative)
Time frame: 7 days
Synovial IL-6 (pg/ml)
Time frame: 7 days
Synovial cathelicidin LL-37 (μg/ml)
Time frame: 7 days
Synovial calprotectin (ng/ml)
Time frame: 7 days
3 secondary outcomes
Serum and synovial biomarkers cut-off for prosthetic joint infections
Time frame: 2 months
Assessment of antimicrobial resistances of isolated microrganisms
Time frame: 2 months
Assessment of biofilm formation capability of isolated microrganisms
Time frame: 2 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2025.
- Background: PubMed 24780823Pabinger C, Geissler A. Utilization rates of hip arthroplasty in OECD countries. Osteoarthritis Cartilage. 2014 Jun;22(6):734-41. doi: 10.1016/j.joca.2014.04.009. Epub 2014 Apr 26.
- Background: PubMed 26028142Pabinger C, Lothaller H, Geissler A. Utilization rates of knee-arthroplasty in OECD countries. Osteoarthritis Cartilage. 2015 Oct;23(10):1664-73. doi: 10.1016/j.joca.2015.05.008. Epub 2015 May 29.
- Background: PubMed 29573912Brochin RL, Phan K, Poeran J, Zubizarreta N, Galatz LM, Moucha CS. Trends in Periprosthetic Hip Infection and Associated Costs: A Population-Based Study Assessing the Impact of Hospital Factors Using National Data. J Arthroplasty. 2018 Jul;33(7S):S233-S238. doi: 10.1016/j.arth.2018.02.062. Epub 2018 Feb 22.
- Background: PubMed 30977537Schwarz EM, Parvizi J, Gehrke T, Aiyer A, Battenberg A, Brown SA, Callaghan JJ, Citak M, Egol K, Garrigues GE, Ghert M, Goswami K, Green A, Hammound S, Kates SL, McLaren AC, Mont MA, Namdari S, Obremskey WT, O'Toole R, Raikin S, Restrepo C, Ricciardi B, Saeed K, Sanchez-Sotelo J, Shohat N, Tan T, Thirukumaran CP, Winters B. 2018 International Consensus Meeting on Musculoskeletal Infection: Research Priorities from the General Assembly Questions. J Orthop Res. 2019 May;37(5):997-1006. doi: 10.1002/jor.24293. Epub 2019 Apr 25.
- Background: PubMed 30800475Bonanzinga T, Ferrari MC, Tanzi G, Vandenbulcke F, Zahar A, Marcacci M. The role of alpha defensin in prosthetic joint infection (PJI) diagnosis: a literature review. EFORT Open Rev. 2019 Jan 23;4(1):10-13. doi: 10.1302/2058-5241.4.180029. eCollection 2019 Jan.
- Background: PubMed 28046049Kunutsor SK, Beswick AD, Peters TJ, Gooberman-Hill R, Whitehouse MR, Blom AW, Moore AJ. Health Care Needs and Support for Patients Undergoing Treatment for Prosthetic Joint Infection following Hip or Knee Arthroplasty: A Systematic Review. PLoS One. 2017 Jan 3;12(1):e0169068. doi: 10.1371/journal.pone.0169068. eCollection 2017.
- Background: PubMed 23230301Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, Rao N, Hanssen A, Wilson WR; Infectious Diseases Society of America. Executive summary: diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013 Jan;56(1):1-10. doi: 10.1093/cid/cis966.
- Background: PubMed 21938532Parvizi J, Zmistowski B, Berbari EF, Bauer TW, Springer BD, Della Valle CJ, Garvin KL, Mont MA, Wongworawat MD, Zalavras CG. New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011 Nov;469(11):2992-4. doi: 10.1007/s11999-011-2102-9. No abstract available.
- Background: PubMed 24155178Cats-Baril W, Gehrke T, Huff K, Kendoff D, Maltenfort M, Parvizi J. International consensus on periprosthetic joint infection: description of the consensus process. Clin Orthop Relat Res. 2013 Dec;471(12):4065-75. doi: 10.1007/s11999-013-3329-4. Epub 2013 Oct 24. No abstract available.
- Background: PubMed 29551303Parvizi J, Tan TL, Goswami K, Higuera C, Della Valle C, Chen AF, Shohat N. The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria. J Arthroplasty. 2018 May;33(5):1309-1314.e2. doi: 10.1016/j.arth.2018.02.078. Epub 2018 Feb 26.
- Background: PubMed 31455372Han X, Xie K, Jiang X, Wang L, Wu H, Qu X, Yan M. Synovial fluid alpha-defensin in the diagnosis of periprosthetic joint infection: the lateral flow test is an effective intraoperative detection method. J Orthop Surg Res. 2019 Aug 28;14(1):274. doi: 10.1186/s13018-019-1320-9.
- Background: PubMed 29855233Marson BA, Deshmukh SR, Grindlay DJC, Scammell BE. Alpha-defensin and the Synovasure lateral flow device for the diagnosis of prosthetic joint infection: a systematic review and meta-analysis. Bone Joint J. 2018 Jun 1;100-B(6):703-711. doi: 10.1302/0301-620X.100B6.BJJ-2017-1563.R1.
- 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.
Gianluca Giavaresi, MD principal investigator
Istituto Ortopedico Rizzoli
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 Prosthetic Joint Infection, run by Istituto Ortopedico Rizzoli at 1 site in Italy.
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 2 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: looking for participants now, as of the sponsor's last update on 22 Sep 2025. 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 Italy. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gianluca Giavaresi, MD (+39 3774548728, gianluca.giavaresi@ior.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
White blood cell count (WBC, cells/μL) (time frame: 7 days). The study lists 15 primary outcomes in all. 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 NCT04858217, which also lists 19 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 Sep 2025.