Bedtime versus morning use of antihypertensives in frail continuing care residents (BedMed-Frail): protocol for a prospective, randomised, open-label, blinded end-point pragmatic trial

Introduction BedMed-Frail explores risks and benefits of switching antihypertensives from morning to bedtime in a frail population at greater risk of hypotensive adverse effects. Methods and analysis Design: Prospective parallel randomised, open-label, blinded end-point trial. Participants: Hypertensive continuing care residents, in either long-term care or supportive living, who are free from glaucoma, and using >= 1 once daily antihypertensive. Setting: 16 volunteer continuing care facilities in Alberta, Canada, with eligible residents identified using electronic health claims data. Intervention: All non-opted out eligible residents are randomised centrally by the provincial health data steward to bedtime versus usual care (typically morning) administration of once daily antihypertensives. Timing changes are made (maximum one change per week) by usual care facility pharmacists. Follow-up: Via linked governmental healthcare databases tracking hospital, continuing care and community medical services. Primary outcome: Composite of all-cause death, or hospitalisation for myocardial infarction/acute-coronary syndrome, stroke, or congestive heart failure. Secondary outcomes: Each primary outcome element on its own, all-cause unplanned hospitalisation or emergency department visit, non-vertebral fracture and, as assessed roughly 135 days postrandomisation, fall in the last 30 days, deteriorated cognition, urinary incontinence, decubitus skin ulceration, inappropriate or disruptive behaviour a minimum of 4 days per week, and receipt of antipsychotic medication or physical restraints in the last 7 days. Process outcome: Proportion of blood pressure medication doses taken at bedtime (broken down monthly). Primary outcome analysis: Cox-Proportional Hazards Survival Analysis. Sample size: The trial will continue until a projected 368 primary outcome events have occurred. Current status: Enrolment is ongoing with 642 randomisations to date (75% female, mean age 88 years). Ethics and dissemination BedMed-Frail has ethical approval from the University of Alberta Health Ethics Review Board (Pro00086129) and will publish results in a peer-reviewed journal.