BedMed-Frail: Does the Potential Benefit of Bedtime Antihypertensive Prescribing Extend to Frail Populations?

The BedMed trial (led out of the University of Alberta and funded by both Alberta Innovates Health Solutions, and the Canadian Institutes for Health Research) is a pragmatic multi-provincial trial intended to determine whether bedtime antihypertensive use, as compared to conventional morning use, reduces major adverse cardiovascular events in community dwelling primary care patients. BedMed-Frail, led by the same group of investigators, is a complementary but separate randomized trial evaluating whether the risks and benefits of bedtime antihypertensive use differ in a long-term care (LTC) population. To accomplish this, within participating Alberta LTC and supportive living facilities, eligible residents with hypertension will be randomized at the patient level to the antihypertensive medication timing intervention (i.e. bedtime versus continued morning use). Trial outcomes and baseline characteristics are drawn from routinely collected electronic health data - using both provincial administrative health claims data and the Resident Assessment Instrument Minimum Data Set (RAI-MDS), which is a standard instrument for collecting clinical information in Canadian LTC facilities. BedMed-Frail is event driven, receiving quarterly reporting of total events from the Alberta Support for Patient Oriented Research (SPOR) Unit's Data Platform. Funding permitting, the trial will continue until observation of 368 primary outcome events. Upon observation of half that number, an independent data safety monitoring board (IDSMB) chaired by Dr. James Wright (Cochrane Hypertension Review Group Co-ordinating Editor) will examine all available outcomes. If p is ≤ 0.001 for benefit (the Haybittle-Peto boundary - recommended to reduce the chance of stopping too early and magnifying benefit), or if p is ≤ 0.05 for harm, the IDSMB will apply clinical judgement and make recommendations to the steering committee on whether the trial should break early. The outcomes of BedMed-Frail are primarily designed to be analogous to the cardiovascular and safety outcomes monitored for in the community BedMed study. However BedMed-Frail is also examining for differences in behaviour issues between groups. Both behavioural problems, and blood pressure, have circadian rhythms. Blood pressure is normally lower overnight and behavioural problems in long term care residents typically worsen during the same period - a phenomenon known as "sundowning". Conceivably, there could be a relationship between the two such that behaviour problems might improve, or worsen, with bedtime antihypertensive use.