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The BedMed trial evaluates whether bedtime antihypertensive administration, as compared with conventional morning use, reduces major adverse cardiovascular events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      <jats:bold>Design<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>Prospective randomised, open-label, blinded end-point trial.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Participants<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>Hypertensive primary care patients using blood pressure lowering medication and free from glaucoma.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Setting<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>Community primary care providers in 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario) are mailing invitations to their eligible patients. Social media campaigns (Google, Facebook) are additionally running in the same provinces.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Intervention<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>Consenting participants are allocated via central randomisation to bedtime vs morning use of all antihypertensives.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Follow-up<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>(1) Telephone or email questionnaire at 1\u2009week, 6\u2009weeks, 6\u2009months and every 6\u2009months thereafter, and (2) accessing linked governmental healthcare databases tracking hospital and community medical services.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Primary outcome<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>Composite of all-cause death, or hospitalisation for myocardial infarction\/acute-coronary syndrome, stroke or congestive heart failure.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Secondary outcomes<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>Each primary outcome element on its own, all-cause hospitalisation or emergency department visit, long-term care admission, non-vertebral fracture, new glaucoma diagnosis, 18-month cognitive decline from baseline (via Short Blessed Test).<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Select other outcomes<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>Self-reported nocturia burden at 6\u2009weeks and 6\u2009months (no, minor or major burden), 1-year self-reported overall health score (EQ-5D-5L), self-reported falls, total cost of care (acute and community over study duration) and mean sleep-time systolic blood pressure after 6\u2009months (via 24-hour monitor in a subset of 302 sequential participants).<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Primary outcome analysis<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>Cox proportional hazards survival analysis.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Sample size<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>The trial will continue until a projected 254 primary outcome events have occurred.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Current status<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>Enrolment ongoing (3227 randomised to date).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>BedMed has ethics approval from six research ethics review boards and will publish results in a peer-reviewed journal.<\/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=\"NCT02990663\">NCT02990663<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-059711","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T12:07:44Z","timestamp":1645704464000},"page":"e059711","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Bedtime versus morning use of antihypertensives for cardiovascular risk reduction (BedMed): protocol for a prospective, randomised, open-label, blinded end-point pragmatic 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