Clinical trial NCT04773054: Identification of Infections in Hip Arthroplasty Loosening.
Official title: Application of Advanced High-sensitivity Technologies for Identifying Infections in Patients With Aseptic Loosening of Hip Arthroplasty.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Loosening, Prosthesis
Keywords: Hip arthroplasty
Infection
Microbiota
Next Generation Sequencing
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2021-02-26
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hospitalized patients admitted at the 1st Orthopaedic and Traumatology Unit of the Istituto Ortopedico Rizzoli (Bologna, Italy).

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Identification of microorganisms by microbiological cultures (number of patients with positive microbiological culture).
timeFrame: Within two week of admission
measure: Number of patients with histological features of periprosthetic infection
timeFrame: Within two week of admission
measure: Identification of microorganisms by next-generation sequencing (NGS) (number of patients with positive NGS).
timeFrame: Through study completion, an average of 6 months.
Secondary outcomes:
measure: Characterization of taxonomic and phylogenetic affiliation of gut microbiota
timeFrame: Through study completion, an average of 6 months.
measure: Characterization of alpha-diversity and beta-diversity of gut microbiota
timeFrame: Through study completion, an average of 6 months.
measure: Characterization of taxonomic and phylogenetic affiliation of oral microbiota
timeFrame: Through study completion, an average of 6 months.
measure: Characterization of alpha-diversity and beta-diversity of oral microbiota
timeFrame: Through study completion, an average of 6 months.
measure: Number of patients with inflammatory cellular reactivity related to bacterial products.
timeFrame: Through study completion, an average of 6 months.
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
Study officials:
affiliation: University of Bologna, Istituto Ortopedico Rizzoli
name: Nicola Baldini
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.