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. TRIAL REGISTRATION NUMBER: NCT04054648.

Tolerability of bedtime diuretics: a prospective cohort analysis.

OBJECTIVES: We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia. DESIGN: Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration. SETTING: 352 community family practices across 4 Canadian provinces between March 2017 and September 2020. PARTICIPANTS: 552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics. INTERVENTION: Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks. RESULTS: At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p<0.0001; NNH 8.0), and more diuretic users considered nocturia a major burden (15.6% vs 1.3%; difference 14.2%; 95% CI 8.9% to 20.6%; p<0.0001; NNH 7.0). Compared with baseline, diuretic users experienced 1.0 more overnight urinations/week (95% CI 0.0 to 1.75; p=0.01). Results did not differ between sexes. CONCLUSIONS: Switching diuretics to bedtime did promote nocturia, but only 15.6% found nocturia a major burden. At 6 months, 77.3% of diuretic users were adherent to bedtime dosing. Bedtime diuretic use is viable for many hypertensive patients, should it ever become clinically indicated. TRIAL REGISTRATION NUMBER: NCT02990663.