Clinical trial NCT04251377: Single-stage Surgery With Antibiotic-loaded Hydrogel Coated Implants Versus Two Stage Surgery for Secondary Prevention of Complex Chronic Periprosthetic Hip Joint Infection
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hip Prosthesis Infection
Keywords: Surgery
Biofilm inhibitor
Chronic infections
Total Hip Arthroplasties (THA)
Defensive Antibacterial Coating (DAC®)
Novagenit®
Hip Prosthesis
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2020-01-31
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Recurrence of clinically diagnosed infection relapse of the periprosthetic joint
timeFrame: Years : 2
Secondary outcomes:
measure: Harris Hip Score (HHS) results
timeFrame: Years : 2
measure: Postel-Merle d'Aubigné (PMA) results
timeFrame: Years : 2
measure: Hip dysfunction and Osteoarthritis Outcome Score (HOOS) results
timeFrame: Years : 2
measure: Oxford-12 results
timeFrame: Years : 2
measure: Death rate (%)
timeFrame: Years : 2
measure: Post-operative complications
timeFrame: Years : 2
measure: Revision surgery for any cause other than infection
timeFrame: Years : 2
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Caen
country: France
facility: CHU Caen
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Dijon
country: France
facility: CHU Dijon
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: HCL - Hôpital de la Croix Rousse
city: Lyon
country: France
facility: HCL - Hôpital Edouard Herriot
city: Marseille
country: France
facility: CHU Marseille
city: Nancy
country: France
facility: CHU Nancy
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: CHU Nice
city: Saint-etienne
country: France
facility: Chu Saint-Etienne
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: CHU SAINT-ETIENNE
name: Bertrand BOYER, MD
role: PRINCIPAL_INVESTIGATOR
References: