Single-stage surgery with antibiotic-loaded hydrogel-coated implants versus two-stage surgery for chronic periprosthetic hip joint infection in French tertiary referral hospitals: the SINBIOSE-H non-inferiority, randomised, controlled trial study protocol.

Introduction: Chronic hip prosthetic joint infection (PJI) treatment needs non-conservative surgery. The recommended treatment follows a two-stage protocol. Between the two surgeries, full-weight bearing is prohibited, and joint stiffness and pain are rather usual complications. The single-stage procedure is thought to be less susceptible to late functional complications with a shorter, single hospital stay. However, infection control could be less efficient; the protocol highly relies on antibiotics and has a list of contra-indications. Most of these contra-indications are directly related to the biofilm formation. As no randomised control trial has ever compared single-stage versus two-stage surgery on infection treatment, the level of evidence for recommending one procedure over the other is low. An antibiotic-loaded hydrogel coating (Defensive Antiadhesive Coating (DAC), Novagenit SRL) has been proven to mechanically prevent biofilm formation while allowing a prolonged intra-articular antibiotic release. The addition of this biofilm inhibitor to a single-stage surgery might stand as a promising strategy for PJI. Moreover, using this device to prevent biofilm formation could expand one-stage surgery to patients who are in theory contra-indicated to one-stage surgery.

Methods And Analysis: SINBIOSE-H is a Prospective Randomized Open, Blinded End-point clinical trial that will include patients with a chronic hip PJI as defined by the Musculoskeletal Infection Society (MSIS), with at least one theoretical contra-indication for single-stage surgery. Patients needing a cemented implant will not be included. 440 patients will be randomised in two groups: the experimental group is composed of single-stage procedure associated with the use of biofilm inhibitor (DAC) loaded with topical antibiotics, and the control group is composed of two-stage procedure without biofilm inhibitor. The primary objective will be to demonstrate that single-stage surgery with antibiotic-loaded hydrogel-coated implants is non-inferior to two-stage surgery for chronic hip PJI treatment. The secondary objectives will be to demonstrate that single-stage surgery with antibiotic-loaded hydrogel-coated implants is superior to two-stage surgery on the prevention of functional complications, patient satisfaction scores, death rate, postoperative complications or early revision surgery for any cause other than infection. Based on a failure rate of two-stage surgery of 20% and a reduction of the infection rate using the DAC biofilm inhibitor from 3 to 0.7%, with a non-inferiority margin of 1.35 and power set at 90%, we estimated to enrol 420 patients.

Ethics And Dissemination: The protocol is in accordance with ethical principles established by the Helsinki World Medical Assembly and its amendments and will be conducted in accordance with the recommendations of International Conference on Harmonisation Good Clinical Practice. A core information and informed consent form will be provided. The written approval of the Ethics Committee (EC)/Institutional Review Board (IRB) together with the approved subject information/informed consent forms must be filed in the study files. Written informed consent must be obtained before any study-specific procedure takes place. The data will be saved on the internal network in a secured directory, dedicated to the study. At the end of the research, all documents (case report files, investigator files, etc) will be archived and stored for 15 years in each centre. Data on SAEs will be included in the study documentation file. All data and documents will be made available if requested by relevant authorities. The EC and IRB were submitted and approved in France (CPP Ile De France X, 93 602 AULNAY-SOUS-BOIS). Ethics approval covers all centres.

Trial Registration Number: The study is registered on clinicaltrials.org under NCT04251377 (EUDRACT NUMBER, 2019-A01491-56; trial sponsor, St Etienne University Hospital Center; date of the last version, 24 February 2006).