{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T05:50:29Z","timestamp":1781329829564,"version":"3.54.1"},"reference-count":33,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"unspecified","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["CSASI18may-0001"],"award-info":[{"award-number":["CSASI18may-0001"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001352","name":"National University of Singapore","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100001352","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,4,27]]},"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Although treatment of obstructive sleep apnoea (OSA) using continuous positive airway pressure (CPAP) reduces blood pressure (BP), adherence to CPAP is often suboptimal. A mandibular advancement device (MAD) is a guideline-endorsed alternative therapy for OSA. Still, there is limited evidence on the relative efficacy between MAD and CPAP on BP reduction. We evaluate whether treatment of moderate-to-severe OSA using MAD can improve BP and other health-related outcomes compared with CPAP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This is a randomised, controlled, non-inferiority trial conducted. We will recruit 220 Asians with a history of hypertension and high cardiovascular risk for an overnight polysomnography screening. Those with moderate-to-severe OSA (apnoea\u2013hypopnoea index \u226515 events\/hour) will be randomised to treatment with either MAD or CPAP in a 1:1 ratio. Stratified by age (60 vs &lt;60 years old), body mass index (25 vs &lt;25\u2009kg\/m<jats:sup>2<\/jats:sup>) and apnoea\u2013hypopnoea index (30 vs &lt;30 events\/hour), an adaptive randomisation scheme with permuted blocks constructed in real-time is implemented to restrict imbalance. The overall study duration is 12 months. The primary endpoint is the 24-hour mean arterial BP difference between baseline and 6-month follow-up. The secondary endpoints include other measures of ambulatory BP monitoring, arrhythmia based on a 4-day electrocardiographic monitoring, biomarker and proteomic analysis, cardiovascular magnetic resonance-derived myocardial fibrosis and remodelling and quality-of-life questionnaires. Recruitment began in October 2019 and ended in December 2022. Comparison between MAD and CPAP will be performed using covariance (ANCOVA) analysis of the changes in 24-hour mean arterial BP while adjusting for the baseline 24-hour mean arterial BP. We will compare the 95% CIs around the treatment difference point estimate with the prespecified non-inferiority margin (1.5\u2009mm Hg). If the upper limit of the 95% CI is &lt;1.5\u2009mm Hg and crosses 0, non-inferiority of the MAD relative to CPAP will be established.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>The Domain Specific Review Board-C, National Healthcare Group under approved the study protocol (NHG DSRB Ref: 2019\/00359, approved on 28 August 2019). Study findings will be disseminated to various local, national, and international audiences through abstract presentations and publication in peer-reviewed journals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04119999\">NCT04119999<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-072853","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T11:31:01Z","timestamp":1685532661000},"page":"e072853","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Mandibular advancement device versus CPAP in lowering 24-hour blood pressure in patients with obstructive sleep apnoea and hypertension: the CRESCENT trial protocol"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct04119999","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04119999","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Yi-Hui","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Tereza","family":"Colpani","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Operative Dentistry and Prosthodontics, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew-Pang","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine, National University of Singapore, Singapore"},{"name":"National University Heart Centre, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiang","family":"Loke","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Operative Dentistry and Prosthodontics, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal S","family":"Cheong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, National University Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Kong","sequence":"additional","affiliation":[{"name":"National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin W","family":"Chin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National Heart Centre Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6295-4905","authenticated-orcid":false,"given":"Pipin","family":"Kojodjojo","sequence":"additional","affiliation":[{"name":"Cardiology, National University Heart Centre, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Raffles Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Cistulli","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8777-2705","authenticated-orcid":false,"given":"Chi-Hang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, National University of Singapore, Singapore"},{"name":"National University Heart Centre, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"2025101811225047000_13.5.e072853.1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S2213-2600(19)30198-5","article-title":"Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis","volume":"7","author":"Benjafield","year":"2019","journal-title":"Lancet Respir Med"},{"key":"2025101811225047000_13.5.e072853.2","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/1848375","article-title":"Review of and updates on hypertension in obstructive sleep apnea","volume":"2017","author":"Ahmad","year":"2017","journal-title":"Int J Hypertens"},{"key":"2025101811225047000_13.5.e072853.3","doi-asserted-by":"crossref","unstructured":"Xu L , Keenan BT , Wiemken AS , et al . 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