Implant-Related Infections in Patients With Skeletal Sarcomas

NCT ID: NCT07264296

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-02-05
• Study Completion Date: 2028-01-31

Brief Summary

The aim of this observational study is to gain knowledge on the microbial and immunological factors behind implant-related infections in patients with skeletal sarcoma.

The main research question the project aims to answer is:

• Are immunological factors more important than microbial factors in peri-prosthetic joint infections in orthopaedic oncology patients?

Patients with skeletal sarcoma planned for primary surgery (tumour resection and replacement with a megaprosthesis) will be sampled intraoperatively to obtain a cross-section bone tissue slice at the resection margin, three soft tissue biopsies and joint fluid (if possible). Patients who develop a peri-prosthetic joint infection after their primary surgery will be sampled in a similar manner during revision surgery.

An additional group of patients with periprosthetic joint infection of a hip or knee prosthesis due to osteoarthritis will be sampled during their revision surgery (bone biopsies, soft tissue biopsies and joint fluid, if possible).

Blood samples will be taken from all patients pre-operatively for extensive biochemical and cellular analyses.

Researchers will compare periprosthetic tissues before and after infection. Further, periprosthetic infected tissues in patients treated for skeletal sarcoma will be compared to periprosthetic infected tissues in patientens treated for osteoarthritis. This will be done to attempt to identify host and microbial mechanisms responsible for the increased infection rate in patients with a megaprosthesis due to skeletal sarcoma (infection incidence rate up to 30%) compared to patients with a hip or knee prosthesis due to osteoarthritis (infection incidence rate 1-2%).

Detailed Description

In orthopaedic oncology, the risk and consequences of orthopaedic device related infections (ODRIs) are heightened as the patients often have compromised immune responses due to underlying disease, chemotherapy or radiation. The implants used may be weight-bearing to the extent that they are impossible to remove or exchange in case of infection, and thereby, in worst case, resulting in amputation or death. Compared to the 1-2% incidence of PJI in a non-oncological population with a total hip- or knee prosthesis, patients with a megaprosthesis due to skeletal sarcoma have an infection incidence of 3-25%. Patient-related factors, extensive and repeated surgery and large reconstructive implants likely account for the increased incidence.

To our knowledge no study has evaluated the role of microbiological factors such as the biofilm production and susceptibility in this population. Further, deficient immunological factors in these patients, such as defect neutrophil migration, cytokine expression and phagocyte respiratory burst, involved in the killing of microbes, may provide an environment favouring more virulent phenotypes. Fundamental knowledge on the role of biofilm in this population could add to the improvement in treatment planning and outcome.

Distinguishing causative pathogens from contaminants may be challenging, especially in polymicrobial infections. The addition of metagenomic diagnostics, still sparsely used in clinical practice, may improve sensitivities, but predictive accuracy is still an issue. Comparing the results of conventional microbiological culturing with metagenomic sequencing would be of interest to determine the accuracy of current diagnostic methods.

The present study is an exploratory project addressing the multifactorial nature of PJI focusing on microbial phenotype in patients with skeletal sarcoma. The role of host, microbe and implant factors will be investigated using a set of different methods and compared to cases och PJI in patients will a conventional hip- or knee prosthesis.

Pre-operative blood samples will be taken and samples of peri-prosthetic soft tissue, bone and joint fluid will be collected intra-operatively. Patients will be sampled during their primary operation with a megaprosthesis due to skeletal sarcoma and in case of postoperative PJI, they will be sampled in the same manner during their revision surgery. Patients undergoing a reoperation due to PJI in a conventional total hip- or knee prosthesis will also be sampled with blood, bone, soft tissue and joint fluid intraoperatively.

Descriptive comparisons between (i) periprosthetic tissues and PJI tissues before and after infection in orthopaedic oncology patients, and (ii) PJI tissues in orthopaedic oncology and conventional PJI patients, will be made in regard to the following parameters:

Role of the host:

• Clinical parameters: ASA-score, diabetes, BMI, age, sex, antibiotic use 2 weeks prior to surgery, duration of chemotherapy, type of chemotherapy, chemotherapy cessation, symptom onset in case of infection, implant type, surgery duration, osteosarcoma type, grade and stage, location of surgery, length of resection.
• Biochemistry in blood (complete white blood cell count with differential, density of neutrophils, CRP, procalcitonin, IL-6).
• Histology and immunohistochemistry (FISH for identification of bacteria, inflammatory infiltrates (presence of foreign body giant cells), angiogenesis, tissue necrosis)
• Gene expression (markers related to angiogenesis, inflammation, microbial recognition and tissue necrosis). In selected paraffin-embedded samples, analysis with spatial transcriptomics will be explored.

Role of the pathogen:

• Five tissue cultures for routine culturing (to determine the causative agent) and one additional for bacterial DNA extraction and 16S rRNA gene sequencing.
• Clinical staphylococcal strains isolated from PJI and tumour endoprosthesis at time of infection will be characterised and compared with respect to their phenotypic biofilm production, antimicrobial susceptibility and presence of virulence genes using CV, MBEC and NGS.
• Difference in gene expression of biofilm-related genes between staphylococcal PJI strains (conventional & orthopaedic oncology) when grown on titanium with serum pre-conditioning in vitro.

Conditions

Implant Infection; Skeletal Sarcoma; Hip Arthritis; Prosthesis-Related Infections; Knee Arthritis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Skeletal sarcoma group

Patients who receive a megaprosthesis as a primary procedure for skeletal sarcoma.

No interventions assigned to this group

Periprosthetic joint infection after skeletal sarcoma

Patients with a periprosthetic joint infection after surgery with a megaprosthesis due to skeletal sarcoma.

No interventions assigned to this group

Periprosthetic joint infection after hip/knee replacement due to osteoarthritis

Non-immuncompromised patients with periprosthetic joint infection following a primary total hip or knee replacement.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Patients diagnosed with skeletal sarcoma planned for primary surgery with resection of tumour and replacement with a megaprosthesis.
• Patients operated with a megaprosthesis due to skeletal sarcoma who develop a peri-prosthetic joint infection (PJI).
• Patients diagnosed with PJI after total hip or knee replacement due to osteoarthritis.

Exclusion Criteria

• None in the group of patients with skeletal sarcoma.
• Patients in the PJI group who have a total hip or knee replacement are excluded if they use immunomodulary medication or have a immunodeficiency.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Göteborg University

OTHER

Sponsor Role: collaborator

The Swedish Society of Medicine

OTHER

Sponsor Role: collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role: collaborator

Vastra Gotaland Region

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karin Svensson Malchau, PhD

Role: PRINCIPAL_INVESTIGATOR

Vastra Gotaland Region

Margarita Trobos, Assoc Prof

Role: PRINCIPAL_INVESTIGATOR

Göteborg University

Locations

Ortopedi, Sahlgrenska University Hospital

Gothenburg, , Sweden

Countries

Sweden

Other Identifiers

Dnr 2023-04459-01

Identifier Type: OTHER

Identifier Source: secondary_id

2022-00853

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ALFGBG-978896

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

GLS-973592

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

LU2021-0048

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2023-04459-01

Identifier Type: -

Identifier Source: org_study_id