Single-stage Surgery With Antibiotic-loaded Hydrogel Coated Implants Versus Two Stage Surgery for Secondary Prevention of Complex Chronic Periprosthetic Hip Joint Infection

Study Overview
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Brief Summary
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Each year, around 1500 infected Total Hip Arthroplasties (THA) need non-conservative surgery, remaining an issue for patients and healthcare units. The recommended treatment, relying on cohort reviews and international consensus follows a two-stage protocol. This protocol implies a first surgery to remove all infected implants and at least 6 weeks of antibiotic treatment without implant, then usually an antibiotic-free period and only then a second surgery to put back new implants and start the rehabilitation protocol, with usually more than a week of a second hospital stay. Between both surgeries, full-weight bearing is prohibited and joint stiffness and/or pain are rather usual complications. Failure rate is estimated at 10% in this two-stage strategy. The single-stage procedure (i.e. implanting back a new prosthesis during the same surgery after implant removal, synovectomy and lavage) is thought to be less susceptible to late functional complications (i.e. pain, stiffness and muscle deficiency) with a shorter, single hospital stay. Although, with single-stage surgery, infection control could be less efficient because most pathogens produce during the first hours of infection an antibiotic-resistant layer called biofilm, allowing them to colonize and adhere to foreign objects like implants. This single-surgery protocol thus highly relies on antibiotics and has a list of contra-indications (based on experts' consensus): the presence of damaged soft tissues or a sinus tract, unknown pathogens, difficult to treat micro-organisms, severe immunosuppression and for many surgeons, each time a bone graft is necessary. Most of these contra-indications are directly related to the biofilm. As no randomized control trial has ever compared single-stage versus two-stage surgery, the level of evidence for recommending one procedure over the other is low. We conducted a survey that showed that most of the French reference centers have already switched to single stage surgery for single-stage non contra-indicated cases. An antibiotic-loaded hydrogel coating (Defensive Antiadhesive Coating®, Novagenit SRL), has been proven to mechanically prevent the biofilm formation, while allowing a prolonged intraarticular antibiotic release, in a randomized controlled trial in primary prevention of infection in THA. The addition of this biofilm inhibitor to a single-stage surgery might stand as a promising strategy for secondary prevention of peri-prosthetic hip joint infection. Moreover, using this device to prevent biofilm formation could expand one stage surgery to patients that are normally contra-indicated to one stage surgery.

Official Title
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Single-stage Surgery With Antibiotic-loaded Hydrogel Coated Implants Versus Two Stage Surgery for Secondary Prevention of Complex Chronic Periprosthetic Hip Joint Infection SINBIOSE-H.

Conditions
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Hip Prosthesis Infection

Intervention / Treatment
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* Device: Defensive Antiadhesive Coating DAC®, Novagenit SRL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Social security affiliation Signed informed consent Chronic periprosthetic hip joint infection defined according to the Musculoskeletal Infection Society criteria : Two positive periprosthetic cultures with phenotypically identical organisms or a sinus tract communicating with the joint, or having 3 of 5 minor criteria: Elevated serum C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR); Elevated synovial fluid White Blood Cell (WBC) count or change of ++ on leukocyte esterase test strip; Elevated synovial fluid Polymorphonuclear Neutrophil Percentage (PMN%); Positive histological analysis of periprosthetic tissue; A single positive culture. Exclusion Criteria: Patients with hypersensitivity to hydrogel components (hyaluronic acid and/or poly-lactic acid) known of Defensive Antibacterial Coating (DAC)® Pregnancy or positive pregnancy test (performed in women of childbearing age before inclusion) Life expectancy < 3 months Expected use of a cemented implant by the surgical team (for the treatment surgical protocol) Unable to give informed consent Patients under guardianship or curators Refusal to participate

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-stage surgery + DAC® + topical antibiotics<br>Experimental group is composed of single-stage procedure associated to the use of biofilm inhibitor (Defensive Antibacterial Coating® DAC®) and topical antibiotics=new strategy | Device: Defensive Antiadhesive Coating DAC®, Novagenit SRL<br>* DAC gel, mixed with topical antibiotics is applied on the surface of the implants before implantation, in a sterile environment in the operating room. The topical antibiotics will be added to the reconstituted DAC® gel preparation, at the discretion of the physician, on the basis of pre-operative culture.<br>|
| No Intervention: control group : two-stage surgery<br>Control group is composed of two-stage procedure without biofilm inhibitor (standard protocol) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of clinically diagnosed infection relapse of the periprosthetic joint | The periprosthetic joint infection is defined according to the Musculoskeletal Infection Society criteria: Two positive periprosthetic cultures with phenotypically identical organisms or a sinus tract communicating with the joint, or having 3 of 5 minor criteria: Elevated serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR); Elevated synovial fluid white blood cell (WBC) count; Elevated synovial fluid polymorphonuclear neutrophil percentage (PMN%); Positive histological analysis of periprosthetic tissue; A single positive culture. | Years : 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Harris Hip Score (HHS) results | Harris Hip Score (HHS) contains 10 items with maximum score at 100 for a perfect hip and minimum score at 0 for a very bad result. | Years : 2 | 
| Postel-Merle d'Aubigné (PMA) results | Postel-Merle d'Aubigné (PMA) contains 3 items (pain, mobility and functional hip) with maximum score at 18 for a perfect hip and minimum score at 0 for a very bad result. | Years : 2 | 
| Hip dysfunction and Osteoarthritis Outcome Score (HOOS) results | Hip dysfunction and Osteoarthritis Outcome Score contains 6 items (symptoms, stiffness, pain, function and daily life, sport and leisure activities, quality of life) and measure everyday activities with score from 0 to 4. | Years : 2 | 
| Oxford-12 results | Oxford-12 allows to know the feelings of the patient during the last 4 weeks felt from 1 to 5 (satisfaction score). | Years : 2 | 
| Death rate (%) | Analysis of death rate by group. | Years : 2 | 
| Post-operative complications | Analysis of post-operative complications by group. | Years : 2 | 
| Revision surgery for any cause other than infection | Analysis of revision surgery for any cause other than infection. | Years : 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgery, Biofilm inhibitor, Chronic infections, Total Hip Arthroplasties (THA), Defensive Antibacterial Coating (DAC®), Novagenit®, Hip Prosthesis