Identification of Infections in Hip Arthroplasty Loosening.

Loosening, Prosthesis Clinical Trial

Official title:

Application of Advanced High-sensitivity Technologies for Identifying Infections in Patients With Aseptic Loosening of Hip Arthroplasty.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04773054
• Other study ID #: TAS-ASEPTIC
• Status: Completed
• Start date: February 8, 2022
• Est. completion date: February 15, 2024

Study information

• Verified date: March 2024
• Source: Istituto Ortopedico Rizzoli
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recent data showed that the rate of periprosthetic infections in patients undergoing a hip arthroplasty revision for aseptic loosening is higher than what can be ascertained with conventional methods. The study aims to assess the adequacy of next-generation sequencing of 16s ribosomal ribonucleic acid (rRNA) gene amplicons for identifying occult infections and improving the diagnostic workup. Moreover, additional testing has been planned in order to increase knowledge on the etiopathogenesis of infection.

Description:

Periprosthetic infection following hip arthroplasty is one of the main causes of implant failure that leads to multiple surgical interventions, prolonged hospitalization, and higher complication rate and mortality. Recent data prove that the rate of periprosthetic infections is higher than what can be ascertained with conventional techniques and highlight as analytical methods that allow an early and accurate diagnosis may help clinicians identify effective treatment and mitigate the devastating consequences. New technologies based on culture-independent assays, i.e., the next-generation sequencing (NGS) of 16s rRNA gene amplicons, have entered medical microbiology as an alternative to traditional bacterial identification methods. NGS has been proven to detect microorganisms in culture-negative periprosthetic joint infection and seems to be a valid adjunct in identifying causative pathogens in samples from patients undergoing a hip arthroplasty revision for aseptic loosening. The microbiota profiling using NGS may also help identify patients prone to develop infections. In predisposing clinical conditions, i.e., obesity and diabetes, the metabolic and nutritional alterations modify the composition and the immunomodulatory properties of intestinal microbiota. Saprophytic, non-pathogenic microorganisms usually found in the intestine and oral cavity can be transferred to other areas becoming a potential source of periprosthetic infection. Additionally, microorganisms may live in the periprosthetic microenvironment without giving signs of overt infection. However, bacterial products, i.e., "microbe-associated molecular patterns" (MAMPs) or "pathogen-associated molecular patterns "(PAMPs), adhere to the implant surface or the wear particles and may elicit a local inflammatory response characterized by the presence of cells capable of producing cytokines that promote osteoclastogenesis, periprosthetic resorption and consequent loosening of the implant. In summary, the current knowledge suggests that the hip arthroplasty loosening, classified as aseptic according to the preoperative clinical and laboratory investigations, could be directly or indirectly associated with infectious pathogenesis even if the microbial cultures on periprosthetic tissues are negative. The investigators designed a small-scale study to assess the adequacy of NGS for identifying occult infections and improving the diagnostic workup in patients undergoing a hip arthroplasty revision for aseptic loosening. Moreover, additional testing has been planned to enhance knowledge on the role of unusual or difficult-to-cultivate microorganisms in the etiopathogenesis of implant failure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: February 15, 2024
• Est. primary completion date: December 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Hip arthroplasty revision for aseptic loosening, diagnosis determined as probable according

to the following criteria:

• pain and/or functional impairment;
• radiographic signs of osteolysis following wear of the implant components, or cortical reaction, or periprosthetic bone resorption;
• negative evaluation by the infectious disease specialist.

Exclusion Criteria:

• presence of a sinus tract communicating with the arthroplasty;
• bacteria isolation from aspirates or blood cultures performed preoperatively;
• serum C-reactive protein higher than 10 mg/L;
• recurrent implant dislocations;
• prosthetic fracture;
• medical history for septic arthritis, osteomyelitis;
• infections in anatomic areas other than hip;
• antibiotic therapy in the 15 days prior to surgery (with the exception of preoperative antibiotic prophylaxis);
• chronic treatment with immunosuppressive drugs;
• medical contraindications for executing sample collection.

Related Conditions & MeSH terms

• Infections
• Loosening, Prosthesis
• Prosthesis Failure

Intervention

Diagnostic Test:
• Microbiological analysis of periprosthetic tissue
Microbiological culture of tissue samples collected intraoperatively from the newly-formed joint capsule, between prosthesis stem and femoral bone, and between the acetabular prosthesis and iliac bone.
• Histological analysis of periprosthetic tissue
Histological assessment of cellular reactivity associated with the infection on tissue samples collected intraoperatively from the newly-formed joint capsule, between prosthesis stem and femoral bone, and between the acetabular prosthesis and iliac bone.

Other:
• Characterization of tissue microbiota
Assessment of tissue microbiome composition using the "next-generation sequencing" of DNA extracted from samples collected intraoperatively from the newly-formed joint capsule, between prosthesis stem and femoral bone, and between the acetabular prosthesis and iliac bone.
• Characterization of gut microbiota
Assessment of gut microbiome composition using the "next-generation sequencing" of DNA extracted from stool samples.
• Characterization of oral microbiota
Assessment of oral microbiome composition using the "next-generation sequencing" of DNA extracted from a buccal swab obtained by rubbing the mucosa of cheeks, gingivae, and palate.

Locations

Country	Name	City	State
Italy	Istituto Ortopedico Rizzoli	Bologna

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Ortopedico Rizzoli

Country where clinical trial is conducted

Italy, 

References & Publications (3)

Goswami K, Parvizi J. Culture-negative periprosthetic joint infection: is there a diagnostic role for next-generation sequencing? Expert Rev Mol Diagn. 2020 Mar;20(3):269-272. doi: 10.1080/14737159.2020.1707080. Epub 2019 Dec 24. No abstract available. — View Citation

Pajarinen J, Jamsen E, Konttinen YT, Goodman SB. Innate immune reactions in septic and aseptic osteolysis around hip implants. J Long Term Eff Med Implants. 2014;24(4):283-96. doi: 10.1615/jlongtermeffmedimplants.2014010564. — View Citation

Tarabichi M, Shohat N, Goswami K, Alvand A, Silibovsky R, Belden K, Parvizi J. Diagnosis of Periprosthetic Joint Infection: The Potential of Next-Generation Sequencing. J Bone Joint Surg Am. 2018 Jan 17;100(2):147-154. doi: 10.2106/JBJS.17.00434. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of microorganisms by microbiological cultures (number of patients with positive microbiological culture).	Tissue samples will be sent for microbiological cultures and treated for the isolation of aerobic and anaerobic pathogens. The existence of two positive cultures will be considered to be diagnostic for periprosthetic infection; a single positive culture may occur from a contaminating organism and will be considered in conjunction with other markers of infection, including histological features.	Within two week of admission
Primary	Number of patients with histological features of periprosthetic infection	The presence of a periprosthetic infection will be established according to the number of polymorphonuclear cells (PMN) counted in ten high-power fields (HPF) (400 × magnification, field diameter 0.54 mm)- Uninfected: 0-5 PMNs in 10 HPFs; borderline, but probably not infected: 6-10 PMNs for 10 HPF; borderline, but probably infected: >10 PMNs for 10 HPFs (but not > 5 PMNs in a single HPF); infected > 5 for HPF.	Within two week of admission
Primary	Identification of microorganisms by next-generation sequencing (NGS) (number of patients with positive NGS).	The NGS will be employed to characterize the overall microbiome profile in tissue samples, and bioinformatics used to determine the taxonomic and phylogenetic affiliation, alpha-diversity (ecological diversity of a single sample according to the number of different taxa and their relative abundances), and beta-diversity (differences in microbial community composition between samples).	Through study completion, an average of 6 months.
Secondary	Characterization of taxonomic and phylogenetic affiliation of gut microbiota	The NGS technology will be employed to characterize the overall microbiome profile in stool samples, and bioinformatics used to determine the taxonomic and phylogenetic affiliation.	Through study completion, an average of 6 months.
Secondary	Characterization of alpha-diversity and beta-diversity of gut microbiota	The NGS technology will be employed to characterize the overall microbiome profile in stool samples, and bioinformatics used to determine alpha-diversity (ecological diversity of a single sample according to the number of different taxa and their relative abundances) and beta-diversity (differences in microbial community composition between samples).	Through study completion, an average of 6 months.
Secondary	Characterization of taxonomic and phylogenetic affiliation of oral microbiota	The NGS technology will be employed to characterize the overall microbiome profile in oral swab, and bioinformatics used to determine the taxonomic and phylogenetic affiliation.	Through study completion, an average of 6 months.
Secondary	Characterization of alpha-diversity and beta-diversity of oral microbiota	The NGS technology will be employed to characterize the overall microbiome profile in oral swab, and bioinformatics used to determine alpha-diversity (ecological diversity of a single sample according to the number of different taxa and their relative abundances) and beta-diversity (differences in microbial community composition between samples	Through study completion, an average of 6 months.
Secondary	Number of patients with inflammatory cellular reactivity related to bacterial products.	The inflammatory cellular reactivity proved by the presence of activated macrophages and Toll-like-receptor positive cells.	Through study completion, an average of 6 months.