{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:08:02Z","timestamp":1790057282030,"version":"4.0.1"},"reference-count":34,"publisher":"BMJ","issue":"9","funder":[{"name":"French Ministry of Health"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2017,9,4]]},"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention and the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long-term outcomes of patients with TBI is uncertain. The aim of the COBI study (number clinicaltrial.gov 03143751, pre-results stage) is to assess the efficiency and the safety of continuous hyperosmolar therapy in patients with TBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The COBI (COntinuous hyperosmolar therapy in traumatic Brain-Injured patients) trial is a multicentre, randomised, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalised in intensive care unit with a TBI (Glasgow Coma Scale \u226412\u2009and abnormal brain CT scan) are randomised in the first 24\u2009hours following trauma to standard care or continuous hyperosmolar therapy (20% NaCl) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48\u2009hours in the treatment group and continued for as long as is necessary to prevent ICH. The primary outcome is the score on the Extended Glasgow Outcome Scale at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common OR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The COBI trial protocol has been approved by the ethics committee of Paris Ile de France VIII and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The COBI trial is the first randomised controlled trial powered to investigate whether continuous hyperosmolar therapy in patients with TBI improve long-term recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      Trial registration number is\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"NCT03143751\" ext-link-type=\"clintrialgov\">NCT03143751<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2017-018035","type":"journal-article","created":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T20:10:18Z","timestamp":1506370218000},"page":"e018035","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["COBI (COntinuous hyperosmolar therapy for traumatic Brain-Injured patients) trial protocol: a multicentre randomised open-label trial with blinded adjudication of primary outcome"],"prefix":"10.1136","volume":"7","clinical-trial-number":[{"clinical-trial-number":"nct03143751","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03143751","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03143751","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Antoine","family":"Roquilly","sequence":"first","affiliation":[{"name":"Anaesthesia Intensive Care Unit, Centre Hospitalier Universitaire, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigismond","family":"Lasocki","sequence":"additional","affiliation":[{"name":"Anaesthesia Intensive Care Unit, Centre Hospitalier Universitaire, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Denis","family":"Moyer","sequence":"additional","affiliation":[{"name":"Anaesthesia Intensive Care Unit, Centre Hospitalier Universitaire de Beaujon (AP\/HP), Beaujon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Huet","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Anaesthesia, Centre Hospitalier Universitaire, Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre Fran\u00e7ois","family":"Perrigault","sequence":"additional","affiliation":[{"name":"Anaesthesia Intensive Care Unit, Centre Hospitalier Universitaire, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Dahyot-fizelier","sequence":"additional","affiliation":[{"name":"Anaesthesia and Intensive Care Unit, Centre Hospitalier Universitaire, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Seguin","sequence":"additional","affiliation":[{"name":"Anaesthesia and Intensive Care Unit, Centre Hospitalier Universitaire, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Sharshar","sequence":"additional","affiliation":[{"name":"Anaesthesia and Intensive Care Unit, H\u00f4pital Saint Anne (AP\/HP), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Geeraerts","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, University Hospital of Toulouse, TONIC (Toulouse NeuroImaging Center), University Toulouse 3-Paul Sabatier, Inserm, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Remerand","sequence":"additional","affiliation":[{"name":"Service anesth\u00e9sie R\u00e9animation 2, Centre Hospitalier R\u00e9gional Universitaire de Tours, Universit\u00e9 F Rabelais, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Feuillet","sequence":"additional","affiliation":[{"name":"D\u00e9partement Promotion, Centre Hospitalier Universitaire de Nantes, Plateforme de M\u00e9thodologie et de Biostatistique, Direction de la Recherche, Nantes, France"},{"name":"Universit\u00e9 de Nantes, Universit\u00e9 de Tours, INSERM, SPHERE U1246, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Asehnoune","sequence":"additional","affiliation":[{"name":"Anaesthesia Intensive Care Unit, Centre Hospitalier Universitaire, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2017,9,24]]},"reference":[{"key":"2025121409063298000_7.9.e018035.1","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1016\/S0140-6736(16)00648-6","article-title":"Global burden of diseases, injuries, and risk factors for young people\u2019s health during 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 2013","volume":"387","author":"Mokdad","year":"2016","journal-title":"Lancet"},{"key":"2025121409063298000_7.9.e018035.2","doi-asserted-by":"publisher","DOI":"10.3109\/02699052.2015.1063692"},{"key":"2025121409063298000_7.9.e018035.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2011.03590.x"},{"key":"2025121409063298000_7.9.e018035.4","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70144-4"},{"key":"2025121409063298000_7.9.e018035.5","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s00134-017-4764-6","article-title":"A multi-faceted strategy to reduce ventilation-associated mortality in brain-injured patients. The BI-VILI project: a nationwide quality improvement project","volume":"43","author":"Asehnoune","year":"2017","journal-title":"Intensive Care Med"},{"key":"2025121409063298000_7.9.e018035.6","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201301-0116OC"},{"key":"2025121409063298000_7.9.e018035.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60864-2"},{"key":"2025121409063298000_7.9.e018035.8","doi-asserted-by":"publisher","DOI":"10.1089\/08977150150502569"},{"key":"2025121409063298000_7.9.e018035.9","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-012-2655-4"},{"key":"2025121409063298000_7.9.e018035.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1207363"},{"key":"2025121409063298000_7.9.e018035.11","unstructured":"Carney N , Totten AM , O\u02bcReilly C , et al . Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery\u00a02016:1\u201310."},{"key":"2025121409063298000_7.9.e018035.12","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-007-0091-7"},{"key":"2025121409063298000_7.9.e018035.13","doi-asserted-by":"crossref","first-page":"R260","DOI":"10.1186\/cc10522","article-title":"Continuous controlled-infusion of hypertonic saline solution in traumatic brain-injured patients: a 9-year retrospective study","volume":"15","author":"Roquilly","year":"2011","journal-title":"Crit Care"},{"key":"2025121409063298000_7.9.e018035.14","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31819c1933"},{"key":"2025121409063298000_7.9.e018035.15","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318218a390"},{"key":"2025121409063298000_7.9.e018035.16","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1007\/s12630-016-0633-y","article-title":"The effect of continuous hypertonic saline infusion and hypernatremia on mortality in patients with severe traumatic brain injury: a retrospective cohort study","volume":"63","author":"Tan","year":"2016","journal-title":"Can J Anaesth"},{"key":"2025121409063298000_7.9.e018035.17","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-013-2978-9"},{"key":"2025121409063298000_7.9.e018035.18","first-page":"939","article-title":"Assessing disability after head injury: improved use of the Glasgow Outcome Scale","volume":"89","year":"2009","journal-title":"J Neurosurg"},{"key":"2025121409063298000_7.9.e018035.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2010.11.047"},{"key":"2025121409063298000_7.9.e018035.20","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.annrmp.2004.01.004","article-title":"Version fran\u00e7aise de l\u201centretien structur\u00e9 pour l\u201d\u00e9chelle de devenir de Glasgow (GOS): recommandations et premi\u00e8res \u00e9tudes de validation","volume":"47","author":"Fayol","year":"2004","journal-title":"Annales de R\u00e9adaptation et de M\u00e9decine Physique"},{"key":"2025121409063298000_7.9.e018035.21","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1016\/S0140-6736(15)00386-4","article-title":"Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial","volume":"386","author":"Nichol","year":"2015","journal-title":"Lancet"},{"key":"2025121409063298000_7.9.e018035.22","doi-asserted-by":"publisher","DOI":"10.1186\/cc10240"},{"key":"2025121409063298000_7.9.e018035.23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050165"},{"key":"2025121409063298000_7.9.e018035.24","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2010.1599"},{"key":"2025121409063298000_7.9.e018035.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2009.10.020"},{"key":"2025121409063298000_7.9.e018035.26","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/ALN.0000000000001165","article-title":"Transcranial doppler to predict neurologic outcome after mild to moderate traumatic brain injury","volume":"125","author":"Bouzat","year":"2016","journal-title":"Anesthesiology"},{"key":"2025121409063298000_7.9.e018035.27","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/S1474-4422(17)30117-5","article-title":"Early predictors of outcome after mild traumatic brain injury (UPFRONT): an observational cohort study","volume":"16","author":"van der Naalt","year":"2017","journal-title":"Lancet Neurol"},{"key":"2025121409063298000_7.9.e018035.28","unstructured":"Geeraets T , Velly L , Abdennour L , et al . Management of severe traumatic brain injury (first 24 hours). http:\/\/sfar.org\/prise-en-charge-des-traumatises-craniens-graves-a-la-phase-precoce\/ (accessed 15 Jul 2017)."},{"key":"2025121409063298000_7.9.e018035.29","doi-asserted-by":"publisher","DOI":"10.1097\/00001199-200305000-00003"},{"key":"2025121409063298000_7.9.e018035.30","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1998.15.573"},{"key":"2025121409063298000_7.9.e018035.31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214609"},{"key":"2025121409063298000_7.9.e018035.32","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1102077"},{"key":"2025121409063298000_7.9.e018035.33","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507581"},{"key":"2025121409063298000_7.9.e018035.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2009.10.022"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2017-018035","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T17:06:40Z","timestamp":1765732000000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2017-018035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9]]},"references-count":34,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,9,24]]},"published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1136\/bmjopen-2017-018035"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2017-018035","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9]]}}}