Periprosthetic Joint Infections: Diagnostic Accuracy and Cost-effectiveness Analysis of Serum and Synovial Markers

NCT04858217 | Recruiting DMC

• 1 other identifier: 37/2021/Sper/IOR
• Study Type: observational
• Target: 270
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Prosthetic Joint Infection

Keywords

prosthetic joint infection; biomarker; synovial fluid; serum

Outcome Measures

Primary Outcomes (15)

• White blood cell count (WBC, cells/μL)

  7 days

• Erythrocyte sedimentation rate (ESR, mm/hour)

  7 days

• C-reactive Protein (CRP, mg/L)

  7 days

• D-dimer (ng/ml)

  7 days

• IL-6 (pg/ml)

  7 days

• Procalcitonin (ng/ml)

  2 months

• Soluble Intercellular Adhesion Molecule-1 (sICAM-1, ng/L)

  7 days

• Synovial WBC (sWBC, cells/μL)

  7 days

• Percentage of polymorphonucleates (%PMM, %) in synovial fluid

  7 days

• Synovial C-reactive Protein (sCRP, mg/L)

  7 days

• Synovial alpha-defensin (positive or negative)

  7 days

• Synovial leukocyte esterase (positive or negative)

  7 days

• Synovial IL-6 (pg/ml)

  7 days

• Synovial cathelicidin LL-37 (μg/ml)

  7 days

• Synovial calprotectin (ng/ml)

  7 days

Secondary Outcomes (3)

• Serum and synovial biomarkers cut-off for prosthetic joint infections

  2 months

• Assessment of antimicrobial resistances of isolated microrganisms

  2 months

• Assessment of biofilm formation capability of isolated microrganisms

  2 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istituto Ortopedico Rizzoli: lead
• IRCCS Azienda Ospedaliero-Universitaria di Bologna: collaborator

Study Sites (1)

IRCCS Istituto Ortopedico Rizzoli

Bologna, 40134, Italy

RECRUITING

Related Publications (19)

• 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.

  PMID: 24780823 BACKGROUND

• Pabinger 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.

  PMID: 26028142 BACKGROUND

• Brochin 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.

  PMID: 29573912 BACKGROUND

• Schwarz 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.

  PMID: 30977537 BACKGROUND

• Bonanzinga 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.

  PMID: 30800475 BACKGROUND

• Kunutsor 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.

  PMID: 28046049 BACKGROUND

• Osmon 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.

  PMID: 23230301 BACKGROUND

• Parvizi 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.

  PMID: 21938532 BACKGROUND

• Cats-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.

  PMID: 24155178 BACKGROUND

• Parvizi 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.

  PMID: 29551303 BACKGROUND

• Han 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.

  PMID: 31455372 BACKGROUND

• Marson 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.

  PMID: 29855233 BACKGROUND

• Suen 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.

  PMID: 29305453 BACKGROUND

• Wouthuyzen-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.

  PMID: 29224989 BACKGROUND

• Alvand 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.

  PMID: 28243953 BACKGROUND

• Parvizi J, Gehrke T, Chen AF. Proceedings of the International Consensus on Periprosthetic Joint Infection. Bone Joint J. 2013 Nov;95-B(11):1450-2. doi: 10.1302/0301-620X.95B11.33135.

  PMID: 24151261 BACKGROUND

• De Fine M, Giavaresi G, Fini M, Illuminati A, Terrando S, Pignatti G. The role of synovial fluid analysis in the detection of periprosthetic hip and knee infections: a systematic review and meta-analysis. Int Orthop. 2018 May;42(5):983-994. doi: 10.1007/s00264-018-3865-3. Epub 2018 Mar 9.

  PMID: 29523955 BACKGROUND

• Hajian-Tilaki K. Sample size estimation in diagnostic test studies of biomedical informatics. J Biomed Inform. 2014 Apr;48:193-204. doi: 10.1016/j.jbi.2014.02.013. Epub 2014 Feb 26.

  PMID: 24582925 BACKGROUND

• Moreno et al., Bayesian Cost-Effectiveness Analysis of Medical Treatments. Chapman and Hall/CRC 2019. ISBN 9781138731738

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and synovial fluid specimen

Study Officials

• Gianluca Giavaresi, MD

  Istituto Ortopedico Rizzoli

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gianluca Giavaresi, MD

CONTACT

+39 3774548728; gianluca.giavaresi@ior.it

Milena Fini, MD

CONTACT

+39 0516366786; milena.fini@ior.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2021
• First Posted: April 26, 2021
• Study Start: February 1, 2022
• Primary Completion: June 17, 2025
• Study Completion: March 31, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)