Loosening, ProsthesisNCT04773054
Identification of Infections in Hip Arthroplasty Loosening.
An observational study of Loosening, Prosthesis, run by Istituto Ortopedico Rizzoli at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Loosening, Prosthesis
- What is being tested?
- Microbiological analysis of periprosthetic tissue, Histological analysis of periprosthetic tissue and Characterization of tissue microbiota
- Type of treatment
- Pill or oral medicine
- How many people
- 11 participants
- Where
- 1 siteItaly
- Study dates
- 8 Feb 2022to 15 Feb 2024
- 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: Hospitalized patients admitted at the 1st Orthopaedic and Traumatology Unit of the Istituto Ortopedico Rizzoli (Bologna, Italy).
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Application of Advanced High-sensitivity Technologies for Identifying Infections in Patients With Aseptic Loosening of Hip Arthroplasty.
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.
Read the 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.
- Conditions
- Loosening, Prosthesis
- Being tested
- Microbiological analysis of periprosthetic tissue, Histological analysis of periprosthetic tissue, Characterization of tissue microbiota, Characterization of gut microbiota, Characterization of oral microbiota
- Keywords
- Hip arthroplasty, Infection, Microbiota, Next Generation Sequencing
- Medical subject headings
- Prosthesis Failure, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Microbiological analysis of periprosthetic tissueDiagnostic test
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 tissueDiagnostic test
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.
Characterization of tissue microbiotaOther
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 microbiotaOther
Assessment of gut microbiome composition using the "next-generation sequencing" of DNA extracted from stool samples.
Characterization of oral microbiotaOther
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within two week of admission
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.
Measured: Within two week of admission
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).
Measured: Through study completion, an average of 6 months.
Secondary outcomes (5)
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.
Measured: Through study completion, an average of 6 months.
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).
Measured: Through study completion, an average of 6 months.
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.
Measured: Through study completion, an average of 6 months.
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
Measured: Through study completion, an average of 6 months.
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.
Measured: Through study completion, an average of 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2021
- Study start8 Feb 2022
- Primary completion11 Dec 2023
- Study completion15 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Loosening, ProsthesisStudies 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
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Ortopedico Rizzoli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicola Baldini, Istituto Ortopedico Rizzoli
- Investigators
- Nicola Baldini, Principal investigator, University of Bologna, Istituto Ortopedico Rizzoli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04773054
- Sponsor's protocol ID
- TAS-ASEPTIC
- Status last verified
- Mar 2024
- First submitted
- 16 Feb 2021
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 31858850Tarabichi 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.
PubMed 29342065Pajarinen 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.
PubMed 25747031
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of Advanced High-sensitivity Technologies for Identifying Infections in Patients With Aseptic Loosening of Hip Arthroplasty.
- ClinicalTrials.gov ID
- NCT04773054
- Acronym / sponsor ID
- TAS-ASEPTIC
- Conditions
- Loosening, Prosthesis
- Keywords
- Hip arthroplasty, Infection, Microbiota, Next Generation Sequencing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Istituto Ortopedico RizzoliUniversity, hospital or other
- Study start
- 8 Feb 2022 (actual)
- Primary completion
- 11 Dec 2023 (actual)
- Study completion
- 15 Feb 2024 (actual)
- First posted
- 26 Feb 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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Hospitalized patients admitted at the 1st Orthopaedic and Traumatology Unit of the Istituto Ortopedico Rizzoli (Bologna, Italy).
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Microbiological analysis of periprosthetic tissueMicrobiological 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. | Diagnostic test | – |
| Histological analysis of periprosthetic tissueHistological 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. | Diagnostic test | – |
| Characterization of tissue microbiotaAssessment 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. | Other | – |
| Characterization of gut microbiotaAssessment of gut microbiome composition using the "next-generation sequencing" of DNA extracted from stool samples. | Other | – |
| Characterization of oral microbiotaAssessment 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. | Other | – |
Primary outcome
Identification of microorganisms by microbiological cultures (number of patients with positive microbiological culture).
Time frame: Within two week of admission
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.
Number of patients with histological features of periprosthetic infection
Time frame: Within two week of admission
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.
Identification of microorganisms by next-generation sequencing (NGS) (number of patients with positive NGS).
Time frame: Through study completion, an average of 6 months.
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).
5 secondary outcomes
Characterization of taxonomic and phylogenetic affiliation of gut microbiota
Time frame: Through study completion, an average of 6 months.
Characterization of alpha-diversity and beta-diversity of gut microbiota
Time frame: Through study completion, an average of 6 months.
Characterization of taxonomic and phylogenetic affiliation of oral microbiota
Time frame: Through study completion, an average of 6 months.
Characterization of alpha-diversity and beta-diversity of oral microbiota
Time frame: Through study completion, an average of 6 months.
Number of patients with inflammatory cellular reactivity related to bacterial products.
Time frame: Through study completion, an average of 6 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
- Background: PubMed 31858850Goswami 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.
- Background: PubMed 29342065Tarabichi 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.
- Background: PubMed 25747031Pajarinen 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.
Related trials for Loosening, Prosthesis
RecruitingObservational study
Post-Market Clinical Follow-Up (PMCF) Study Evaluating the Safety and Efficacy of Tıpmed™ Revision Hip Prosthesis System
Revision Hip Arthroplasty, Aseptic Loosening of Prosthetic Joint
Active, not recruitingObservational study
Plasmafit® Revision Structan® Hip Endoprosthesis Cup
Osteolysis, Arthroplasty Complications
Recruiting
Poly vs Hybrid Glenoid in Stemless aTSA
Glenohumeral Osteoarthritis
Not yet recruitingObservational study
Radiographic Stability of Hip Prosthesis Prior to Revision Surgery
Loosening, Prosthesis, Hip Arthropathy
Active, not recruiting
Efficacy of Robot-assisted Technique vs Conventional Technique in Preventing Early Micromobilisation After UKA
Loosening, Prosthesis
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.
Nicola Baldini principal investigator
University of Bologna, 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 Loosening, Prosthesis, 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 4 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: finished, as of the sponsor's last update on 20 Mar 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Identification of microorganisms by microbiological cultures (number of patients with positive microbiological culture). (time frame: Within two week of admission). The study lists 3 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 NCT04773054, which also lists 3 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 20 Mar 2024.