Prospective Study of Patients Treated for Bone and Joint Infection (BJI) Due to Staphylococcus Aureus, Aiming at Identifying Biomarkers of Diagnosis Interest in Chronic BJI (ESPRI-IOAC)

• ClinicalTrials.gov Identifier: NCT04583241
• Recruitment Status: Not yet recruiting
• First Posted: October 12, 2020
• Last Update Posted: October 12, 2020
• Sponsor: Hospices Civils de Lyon
• Information provided by (Responsible Party): Hospices Civils de Lyon

Study Description

Brief Summary:

There are more than one million (> 40,000 cases per year in France) of osteoarticular infections (OAI) yearly in the world. The number of these infections is constantly increasing due to an increase in life expectancy associated with an increase in prosthesis fitting, as well as an increase in comorbid factors. These are severe pathologies associated with mortality (5%) and significant morbidity (40%), responsible for functional sequelae with an individual cost (prolonged hospitalization, altered quality of life, disability) and societal (sick leave, partial disability). or total, temporary or permanent) extremely high. In addition, reinfection rates within two years of treatment are high.

The BJIs are a group of clinical entities that have in common the invasion and progressive destruction of bone and cartilage tissue by bacterial-like microorganisms.

Staphylococcus spp is the main pathogen (>50%) in BJI and is associated with particularly difficult to treat infections, with a high rate of chronicity and relapses, especially in case of implanted material.

The difficulty in managing these infections is partly linked, on the one hand, to the fact that the pathogens are in "persistent" metabolic forms and in intracellular reservoirs which make them insensitive to conventional antibiotics and, on the other hand, the absence of reliable markers of the infection and above all of its clinical resolution, which complicates clinical trials.

ESPRI-IOAC is a consortium of 4 partners (private-public) from Lyon area and which aims at:

• studying the translational value of BJI preclinical models
• identifying biomarkers of infection in preclinical models and at assessing them in a prospective study.

The current study is part of the global ESPRI-IOAC consortium, and represent the clinical application.

It is a prospective study of patients treated for BJI in the infectious disease department of the Hospices Civils de Lyon, La Croix-Rousse, for osteo-articular infections due to Staphylococcus aureus, or for simple mechanical revision or for cruciate ligament surgery, the objective of which is to highlight biomarkers of interest in the diagnosis of chronic BJI and, or predictive of the therapeutic response.

The translational value of the experimental models used in the BJI will also be studied.

Condition or disease	Intervention/treatment
Bone and Join Infection (BJI); Periprosthetic Joint Infection (PJI)	Other: Constitution of serum bank and urine bank at D0; Other: Constitution of serum bank and urine bank during follow-up; Other: ELISA assays of serum and urinary markers of bone remodeling at D0; Other: ELISA assays of serum and urinary markers of bone remodeling during follow-up; Other: Analysis of bacterial gene expression at D0

Study Design

• Study Type: Observational
• Estimated Enrollment: 200 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Prospective Study of Patients Treated for Bone and Joint Infection (BJI) Due to Staphylococcus Aureus, Aiming at Identifying Biomarkers of Diagnosis Interest in Chronic BJI
• Estimated Study Start Date: October 2020
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: April 2024

Groups and Cohorts

Group/Cohort	Intervention/treatment
BJI group; Patients with an BJI on material (prosthesis or other implant) infected by Streptococcus aureus* Patients are follow-up during two years after surgery. *Diagnosis of staphylococcus aureus monoinfection realized a posteriori after surgery on bacteriological sample	Other: Constitution of serum bank and urine bank at D0; Blood samples and urine at Day 0 (day of surgery); Other: Constitution of serum bank and urine bank during follow-up; Blood samples and urine are obtained at week 2, week 6 post-surgery, at the end of antibiotherapy and 6 months post-surgery, only for patients with staphylococcus aureus monoinfection who are follow-up during two years.; Other: ELISA assays of serum and urinary markers of bone remodeling at D0; Assessment by ELISA assays of serum and urinary markers of bone remodelling: the osteocalcin (OC), the procollagen propeptide type 1 (PINP), the cross linked telopeptide of type 1 collagen (CTX1) and the periostin at Day 0 (day of surgery); Other: ELISA assays of serum and urinary markers of bone remodeling during follow-up; Assessment by ELISA assays of serum and urinary markers of bone remodelling: the osteocalcin (OC), the procollagen propeptide type 1 (PINP), the cross linked telopeptide of type 1 collagen (CTX1) and the periostin at week 2, week 6 post-surgery, at the end of antibiotherapy and 6 months post-surgery, only for patients with staphylococcus aureus monoinfection who are follow-up during two years; Other: Analysis of bacterial gene expression at D0; Assessement of bacterial gene expression on surgery residual tissue (bone tissue, joint fluid, fragment of prostheses) collected at Day 0 (day of the surgery)
Control Group With material; Patients with mechanical problems on implanted equipment (control cohort), without infection* Patient of this group are follow-up until surgery. *Diagnosis of staphylococcus aureus monoinfection realized a posteriori after surgery on bacteriological sample	Other: Constitution of serum bank and urine bank at D0; Blood samples and urine at Day 0 (day of surgery); Other: ELISA assays of serum and urinary markers of bone remodeling at D0; Assessment by ELISA assays of serum and urinary markers of bone remodelling: the osteocalcin (OC), the procollagen propeptide type 1 (PINP), the cross linked telopeptide of type 1 collagen (CTX1) and the periostin at Day 0 (day of surgery); Other: Analysis of bacterial gene expression at D0; Assessement of bacterial gene expression on surgery residual tissue (bone tissue, joint fluid, fragment of prostheses) collected at Day 0 (day of the surgery)
Group osteomyelitis; Patients with chronic hematogenous osteomyelitis* Patient of this group are follow-up until surgery. *Diagnosis of staphylococcus aureus monoinfection realized a posteriori after surgery on bacteriological sample	Other: Constitution of serum bank and urine bank at D0; Blood samples and urine at Day 0 (day of surgery); Other: ELISA assays of serum and urinary markers of bone remodeling at D0; Assessment by ELISA assays of serum and urinary markers of bone remodelling: the osteocalcin (OC), the procollagen propeptide type 1 (PINP), the cross linked telopeptide of type 1 collagen (CTX1) and the periostin at Day 0 (day of surgery); Other: Analysis of bacterial gene expression at D0; Assessement of bacterial gene expression on surgery residual tissue (bone tissue, joint fluid, fragment of prostheses) collected at Day 0 (day of the surgery)
Control Group with cruciate ligament surgery; Patients having cruciate ligament surgery Patient of this group are follow-up until surgery.	Other: Constitution of serum bank and urine bank at D0; Blood samples and urine at Day 0 (day of surgery); Other: ELISA assays of serum and urinary markers of bone remodeling at D0; Assessment by ELISA assays of serum and urinary markers of bone remodelling: the osteocalcin (OC), the procollagen propeptide type 1 (PINP), the cross linked telopeptide of type 1 collagen (CTX1) and the periostin at Day 0 (day of surgery); Other: Analysis of bacterial gene expression at D0; Assessement of bacterial gene expression on surgery residual tissue (bone tissue, joint fluid, fragment of prostheses) collected at Day 0 (day of the surgery)

Outcome Measures

Primary Outcome Measures :

1. Dosages of serum and urinary osteocalcin [ Time Frame: At the time of surgery ]
   Comparison of dosages by ELISA test of serum and urinary osteocalcin between the patients with OAI and the "control" patients without OAI at the time of inclusion in order to demonstrate a marker or a combination of markers for OAI.
2. Dosages of serum and urinary procollagen propeptide type 1 [ Time Frame: At the time of surgery ]
   Comparison of dosages by ELISA test of serum and urinary procollagen propeptide type 1 between the patients with OAI and the "control" patients without OAI at the time of inclusion in order to demonstrate a marker or a combination of markers for OAI.
3. Dosages of serum and urinary cross-linked telopeptide of type 1 collagen [ Time Frame: At the time of surgery ]
   Comparison of dosages by ELISA test of serum and urinary cross-linked telopeptide of type 1 collagen between the patients with OAI and the "control" patients without OAI at the time of inclusion in order to demonstrate a marker or a combination of markers for OAI.
4. Dosages of serum and urinary periostin [ Time Frame: At the time of surgery ]
   Comparison of dosages by ELISA test of serum and urinary periostin between the patients with OAI and the "control" patients without OAI at the time of inclusion in order to demonstrate a marker or a combination of markers for OAI.

Biospecimen Retention:   Samples With DNA

• Collection of serum : Blood samples are obtained at different times : Day 0 (day of surgery), and for patients with staphylococcus aureus monoinfection who are follow-up during two years, at week 2, week 6 post-surgery, at the end of antibiotherapy and 6 months post-surgery)
• Tissue bank : Recovery of residual samples of bone tissue, joint fluid, fragment of prostheses the day of surgery
• Urine bank : Urine samples are obtained at different times : Day 0 (day of surgery), and for patients with staphylococcus aureus monoinfection who are follow-up during two years, at week 2, week 6 post-surgery, at the end of antibiotherapy and 6 months post-surgery)

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients treated in the orthopedic surgery and infectious diseases departments of the Hospices Civils de Lyon, Croix-Rousse Hospital, for osteo-articular infections, due to Staphylococcus aureus, for simple mechanical revision or for cruciate ligament surgery.

Criteria

Inclusion Criteria:

• Age ≥ 30 years old
• Hospitalized in orthopedic surgery for one of these reasons:
• A suspected infection or a documented proven infection with staphylococcus aureus on prosthesis or other orthopedic implant
• A mechanical cause (absence of infection) on prosthesis or orthopedic implant
• Documented chronic hematogenous osteomyelitis due to staphylococcus aureus
• Cruciate ligament surgery
• Patient not subject to any legal protection measure
• Patient who can be followed in the Infectious and Tropical Diseases Department, CRIOAC Lyon ("Centre de Référence des Infections Ostéo-Articulaires complexes" = reference centre of bone and joint infections in french), La Croix-Rousse for at least 6 months post-surgery
• Patient who gave his no-opposition
• Patient giving his consent to the creation of biological collections

Exclusion Criteria:

• Polymicrobial infection
• Known inflammatory disease
• Hyperthyroidism
• Cushing's disease
• Osteomalacia
• Renal osteodystrophy
• Paget's disease
• Malignant disease in progress
• Multiple myeloma
• Bone metastases
• Ehlers-Danlos syndrome
• Pregnant or lactating woman
• Renal impairment (Creatinine clearance <60 mL / min)
• Trauma in the 6 months preceding surgery
• Fracture in the 6 months preceding surgery
• Corticosteroid therapy in progress at the time of inclusion
• Active infection with HIV (human immunodeficiency virus), HBV (hepatitis B virus), HCV hepatitis C virus) documented in the patient file
• Antibiotic treatment in the 15 days preceding inclusion
• People placed under judicial protection

Contacts and Locations

Contacts

Contact: Tristan FERRY, Pr; (0)4 72 07 24 81 ext +33; tristan.ferry@chu-lyon.fr

Contact: Sylvie THEVENON; (0)4 26 73 27 28 ext +33; sylvie.thevenon01@chu-lyon.fr

Locations

France

Hôpital Croix Rousse

Lyon, France, 69004

Contact: Tristan FERRY, Pr (0)4 72 07 24 81 ext +33 tristan.ferry@chu-lyon.fr

Contact: Sylvie Thevenon (0)4 26 73 27 28 ext +33 sylvie.thevenon01@chu-lyon.fr

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

• Principal Investigator: Tristan FERRY, Pr; Service Maladies Infectieuses et Tropicales, CRIOAC Lyon

More Information

• Responsible Party: Hospices Civils de Lyon
• ClinicalTrials.gov Identifier: NCT04583241
• Other Study ID Numbers: 69HCL20_0235
• First Posted: October 12, 2020
• Last Update Posted: October 12, 2020
• Last Verified: October 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hospices Civils de Lyon:

BJI; Staphylococcus aureus; biomarkers

Additional relevant MeSH terms:

Infections; Communicable Diseases; Arthritis, Infectious; Disease Attributes; Pathologic Processes; Arthritis; Joint Diseases; Musculoskeletal Diseases