{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T06:14:08Z","timestamp":1794032048076,"version":"4.8.0"},"reference-count":25,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"unspecified","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Minist\u00e8re de la Sant\u00e9 - Direction G\u00e9n\u00e9rale de l\u2019Offre de Soins","award":["2022-A02513-40"],"award-info":[{"award-number":["2022-A02513-40"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,1,24]]},"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>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\u2009602 AULNAY-SOUS-BOIS). Ethics approval covers all centres.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      The study is registered on clinicaltrials.org under\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04251377\">NCT04251377<\/jats:ext-link>\n                      (EUDRACT NUMBER, 2019-A01491-56; trial sponsor, St Etienne University Hospital Center; date of the last version, 24 February 2006).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-085146","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T11:05:42Z","timestamp":1740481542000},"page":"e085146","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["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"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct04251377","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6427-9491","authenticated-orcid":false,"given":"Bertrand","family":"Boyer","sequence":"first","affiliation":[{"name":"SAnt\u00e9 INg\u00e9ni\u00e9rie BIOlogie St-Etienne, Saint-Priest-en-Jarez, France"},{"name":"Department of Orthopedics, St Etienne University Hospital Center, Saint-Priest-en-Jarez, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Cazorla","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, CIC-1408, Saint-Priest-en-Jarez, France"},{"name":"Department of Infectious Diseases and Hygiene, St Etienne University Hospital Center, Saint-Priest-en-Jarez, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Carricajo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, CIC1408, Saint-Priest-en-Jarez, France"},{"name":"Department of Microbiology, Centre International de Recherche en Infectiologie, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Labruyere","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche Clinique Innovation et Pharmacologie, Saint-Priest-en-Jarez, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Chapelle","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Jean Monnet, Saint-\u00c9tienne, France"},{"name":"Unit\u00e9 de Recherche Clinique Innovation et Pharmacologie, Saint-Etienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Presles","sequence":"additional","affiliation":[{"name":"Inserm CIC1408, Saint-Etienne University Hospital Centre, Saint-Etienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-1195","authenticated-orcid":false,"given":"Paul","family":"Zufferey","sequence":"additional","affiliation":[{"name":"University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Botelho-Nevers","sequence":"additional","affiliation":[{"name":"Service d\u2019Infectiologie, CIC-1408 INSERM Vaccinologie, CHU St. Etienne, Saint-Etienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"2025121409552686000_15.2.e085146.1","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1016\/j.arth.2018.01.057","article-title":"Economic Evaluation of Antibacterial Coatings on Healthcare Costs in First Year Following Total Joint Arthroplasty","volume":"33","author":"Trentinaglia","year":"2018","journal-title":"J Arthroplasty"},{"key":"2025121409552686000_15.2.e085146.2","doi-asserted-by":"crossref","first-page":"i37","DOI":"10.1093\/jac\/dku254","article-title":"Impact of bacterial biofilm on the treatment of prosthetic joint infections","volume":"69 Suppl 1","author":"Jacqueline","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2025121409552686000_15.2.e085146.3","doi-asserted-by":"crossref","unstructured":"McPherson EJ , Woodson C , Holtom P , et al . Periprosthetic total hip infection: outcomes using a staging system. Clin Orthop Relat Res 2002;8\u201315.","DOI":"10.1097\/00003086-200210000-00003"},{"key":"2025121409552686000_15.2.e085146.4","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S29025"},{"key":"2025121409552686000_15.2.e085146.5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0139166","article-title":"Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis: A Systematic Review and Meta-Analysis","volume":"10","author":"Kunutsor","year":"2015","journal-title":"PLoS One"},{"key":"2025121409552686000_15.2.e085146.6","first-page":"555","article-title":"Infection as a cause of primary total hip arthroplasty revision and its predictive factors","volume":"99","author":"Reina","year":"2013","journal-title":"Orthopaed Traumatol: Surg Res"},{"key":"2025121409552686000_15.2.e085146.7","doi-asserted-by":"publisher","DOI":"10.3109\/17453674.2010.548025"},{"key":"2025121409552686000_15.2.e085146.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040181"},{"key":"2025121409552686000_15.2.e085146.9","doi-asserted-by":"crossref","DOI":"10.2106\/JBJS.L.01451","article-title":"One-stage exchange arthroplasty for chronic periprosthetic hip infection: results of a large prospective cohort study","volume":"96","author":"Zeller","year":"2014","journal-title":"J Bone Joint Surg Am"},{"key":"2025121409552686000_15.2.e085146.10","first-page":"144","article-title":"Infected total hip arthroplasty revision: One- or two-stage procedure?","volume":"98","author":"Klouche","year":"2012","journal-title":"Orthopaed Traumatol: Surg Res"},{"key":"2025121409552686000_15.2.e085146.11","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis966"},{"key":"2025121409552686000_15.2.e085146.12","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-016-1213-8","article-title":"One-stage or two-stage revision surgery for prosthetic hip joint infection--the INFORM trial: a study protocol for a randomised controlled trial","volume":"17","author":"Strange","year":"2016","journal-title":"Trials"},{"key":"2025121409552686000_15.2.e085146.13","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2022-071281","article-title":"Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial","volume":"379","author":"Blom","year":"2022","journal-title":"BMJ"},{"key":"2025121409552686000_15.2.e085146.14","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-018-3050-8","article-title":"Cost-benefit analysis of antibiofilm microbiological techniques for peri-prosthetic joint infection diagnosis","volume":"18","author":"Roman\u00f2","year":"2018","journal-title":"BMC Infect Dis"},{"key":"2025121409552686000_15.2.e085146.15","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-014-3558-1"},{"key":"2025121409552686000_15.2.e085146.16","doi-asserted-by":"publisher","DOI":"10.1007\/s10195-017-0442-2"},{"key":"2025121409552686000_15.2.e085146.17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.7150\/jbji.15986","article-title":"Does an Antibiotic-Loaded Hydrogel Coating Reduce Early Post-Surgical Infection After Joint Arthroplasty?","volume":"1","author":"Roman\u00f2","year":"2016","journal-title":"J Bone Jt Infect"},{"key":"2025121409552686000_15.2.e085146.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2018.02.078"},{"key":"2025121409552686000_15.2.e085146.19","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00264-018-3763-8","article-title":"The fate of immunocompromised patients in the treatment of chronic periprosthetic joint infection: a single-centre experience","volume":"42","author":"Ji","year":"2018","journal-title":"Int Orthop"},{"key":"2025121409552686000_15.2.e085146.20","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-010-1725-6"},{"key":"2025121409552686000_15.2.e085146.21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s11046-014-9852-3","article-title":"Systemic review of published literature on Candida infection following total hip arthroplasty","volume":"179","author":"Kim","year":"2015","journal-title":"Mycopathologia"},{"key":"2025121409552686000_15.2.e085146.22","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-014-2309-y"},{"key":"2025121409552686000_15.2.e085146.23","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1007\/s00167-018-4896-4","article-title":"One-stage exchange with antibacterial hydrogel coated implants provides similar results to two-stage revision, without the coating, for the treatment of peri-prosthetic infection","volume":"26","author":"Capuano","year":"2018","journal-title":"Knee Surg Sports Traumatol Arthrosc"},{"key":"2025121409552686000_15.2.e085146.24","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-014-2466-z"},{"key":"2025121409552686000_15.2.e085146.25","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s00264-015-2833-4","article-title":"One-stage revision of infected hip arthroplasty: outcome of 39 consecutive hips","volume":"40","author":"Ilchmann","year":"2016","journal-title":"Int Orthop"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-085146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T17:55:33Z","timestamp":1765734933000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-085146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2,25]]},"published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1136\/bmjopen-2024-085146"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-085146","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]}}}