Ignite Creation Date:
2024-05-06 @ 12:26 PM
Last Modification Date:
2024-10-26 @ 12:59 PM
Study NCT ID:
NCT03769337
Status:
UNKNOWN
Last Update Posted:
2018-12-24
First Post:
2018-12-06
Brief Title:
New Markers for Diagnosis of Prosthetic Infections
Sponsor:
IRCCS Ospedale Galeazzi-SantAmbrogio
Organization:
IRCCS Ospedale Galeazzi-SantAmbrogio
Study Overview
Official Title:
Identification of New Biological Marker for Diagnosis of Periprosthetic Infections
Status:
UNKNOWN
Status Verified Date:
2018-11
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Perimarkers
Brief Summary:
Implant infections are among the most dramatic complications in orthopaedic surgery with heavy impact on life quality and health system Their diagnosis is still challenging since till now none othe proposed markers has shown a sensitivity and a specificity of100 Therefore efforts in identification of new markers of infections are required This study aims to evaluate the applicability of Interleukin IL-6 Triggering receptor expressed on myeloid cells TREM-1 CC chemokine ligand 2 CCL2 matrix metalloproteinases MMP-9 osteopontin OPN IL-1 receptor antagonist IL1-RA IL-6 receptor beta GP130 C5a receptor for advanced glycation end products sRAGE urokinases and presepsin as serum markers of prosthetic joint infection
At this purpose serum from 65 patients with infected implant and from 65 with aseptic failure of their prosthesis will be collected before surgery and after 2 and 7 days from revision
At this purpose serum from 65 patients with infected implant and from 65 with aseptic failure of their prosthesis will be collected before surgery and after 2 and 7 days from revision
Detailed Description:
Management of prosthetic joint infections involves long antibiotic therapy and in most cases additional revision surgery with worsening of life quality for patients and high costs for health system Prosthetic joint infections occur at a rate of 1-2 but their incidence grows up to 15-20 after the first revision surgery Gram positive cocci particularly staphylococci are the main pathogens responsible for these infections Diagnostic workflow is rather complicated since a gold standard assay characterized by high sensitivity and specificity has not been recognized Consequently the diagnosis is based on fulfillment of a series of major and minor criteria derived from biochemical hematological microbiological histological analyses combined with clinical and radiological observations Therefore it is evident that there is an urgent need to find early markers of infection characterized by high sensitivity and specificity able to differentiate between aseptic failure and prosthetic joint infections caused by both high and low virulent microorganisms
In the recent years presepsin has been described as a marker for sepsis also able to discriminate sepsis severity Presepsin is a fragment of soluble receptor CD14 which is released from monocyte surface during inflammation The new inflammatory marker TREM-1 links the activity of presepsin to other actors of inflammation process like Toll Like Receptors monocytes inflammatory cytokines like IL-1 and IL-6 the chemokine CCL2 Presepsin activity is also related to suPAR an inflammatory marker we have recently shown to be associated with prosthetic joint infections Another potential marker of infection is osteopontin OPN a multifunctional protein with pro-inflammatory properties which correlates with mortality and is associated to suPAR in inflammatory response Similarly receptor CD163 highly expressed by macrophages during inflammation has been proposed as a promising serum marker of inflammation Equally important in inflammatory process is the role played by neutrophils which represent the first line of defense against infection being able to kill bacteria by producing oxygen reactive species ROS Recently ROS have been correlated with serum Advanced Glycation End ProductsAGEs that are increased by oxidative stress AGEs are able to interact with their receptor RAGE which exists in its soluble forms in plasma For this reason RAGE might be used as serum biomarker to diagnose infection and related oxidative stress Despite the amount of scientific papers on the role of the above mentioned molecules a panel combining them for diagnosis of prosthetic joint infections is not yet available
Aim of the study will be to evaluate new biological markers of prosthetic joint infection in order to improve diagnostic workflow to support and integrate data from microbiological hematological and clinical examination
At this purpose differences in serum concentrations of IL-6 TREM-1 CCL2 MMP-9 OPN IL-1RA GP-130 C5a sRAGE urokinases and presepsin between infected and not infected patients will be evaluated by measuring sensitivity specificity positive and negative predictive values likelihood ratio for each parameter Moreover concentration of each biomarker will be correlated with markers routinely used for diagnosis of these infections
A total of 130 patients will be enrolled in the study 65 patients with diagnosis of aseptic failure and 65 diagnosed with infection of prosthetic implant
All of them will sign an informed consent before enrollment An aliquot of serum sent to the Laboratory for pre- and post-operative 2 and 7 days after surgery routine analyses will be stored at -20C
Serum concentrations of IL-6 TREM-1 CCL2 MMP-9 OPN IL-1RA GP-130 C5a sRAGE urokinase and presepsin will be determined by means of commercially available ELISA assays
Data regarding preoperative Erythrocyte Sedimentation Rate ESR and C-reactive protein CRP Synovial fluid analysis if available both pre and intra operative and microbiological culture implant and periprosthetic tissues will be also collected
In the recent years presepsin has been described as a marker for sepsis also able to discriminate sepsis severity Presepsin is a fragment of soluble receptor CD14 which is released from monocyte surface during inflammation The new inflammatory marker TREM-1 links the activity of presepsin to other actors of inflammation process like Toll Like Receptors monocytes inflammatory cytokines like IL-1 and IL-6 the chemokine CCL2 Presepsin activity is also related to suPAR an inflammatory marker we have recently shown to be associated with prosthetic joint infections Another potential marker of infection is osteopontin OPN a multifunctional protein with pro-inflammatory properties which correlates with mortality and is associated to suPAR in inflammatory response Similarly receptor CD163 highly expressed by macrophages during inflammation has been proposed as a promising serum marker of inflammation Equally important in inflammatory process is the role played by neutrophils which represent the first line of defense against infection being able to kill bacteria by producing oxygen reactive species ROS Recently ROS have been correlated with serum Advanced Glycation End ProductsAGEs that are increased by oxidative stress AGEs are able to interact with their receptor RAGE which exists in its soluble forms in plasma For this reason RAGE might be used as serum biomarker to diagnose infection and related oxidative stress Despite the amount of scientific papers on the role of the above mentioned molecules a panel combining them for diagnosis of prosthetic joint infections is not yet available
Aim of the study will be to evaluate new biological markers of prosthetic joint infection in order to improve diagnostic workflow to support and integrate data from microbiological hematological and clinical examination
At this purpose differences in serum concentrations of IL-6 TREM-1 CCL2 MMP-9 OPN IL-1RA GP-130 C5a sRAGE urokinases and presepsin between infected and not infected patients will be evaluated by measuring sensitivity specificity positive and negative predictive values likelihood ratio for each parameter Moreover concentration of each biomarker will be correlated with markers routinely used for diagnosis of these infections
A total of 130 patients will be enrolled in the study 65 patients with diagnosis of aseptic failure and 65 diagnosed with infection of prosthetic implant
All of them will sign an informed consent before enrollment An aliquot of serum sent to the Laboratory for pre- and post-operative 2 and 7 days after surgery routine analyses will be stored at -20C
Serum concentrations of IL-6 TREM-1 CCL2 MMP-9 OPN IL-1RA GP-130 C5a sRAGE urokinase and presepsin will be determined by means of commercially available ELISA assays
Data regarding preoperative Erythrocyte Sedimentation Rate ESR and C-reactive protein CRP Synovial fluid analysis if available both pre and intra operative and microbiological culture implant and periprosthetic tissues will be also collected
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None