Clinical trial NCT04054648: BedMed-Frail: Does the Potential Benefit of Bedtime Antihypertensive Prescribing Extend to Frail Populations?
Official title: Does the Potential Benefit of Bedtime Antihypertensive Prescribing Extend to Frail Populations? The "BedMed-Frail" Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Dementia
Keywords: Pragmatic
Primary Care
Chronotherapy
Administrative Data
Behaviourism
Sundowning
Stroke
Myocardial Infarction
Heart Failure
Hip Fracture
Nursing Home
Long Term Care
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: Alberta Innovates Health Solutions
name: Canadian Institutes of Health Research (CIHR)
name: EnACt
name: Alberta Health services
First posted: 2019-08-13
Enrollment: 776
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Event-driven Prospective Randomized Open Blinded End-Point (PROBE) Randomized Trial.
Primary purpose: PREVENTION

Brief summary: High blood pressure (present in 1 of 5 Canadian adults) increases the risk of heart attack and stroke. Blood pressure lowering pills reduce this risk - but perhaps not optimally. A Spanish study suggests that using blood pressure pills at bedtime, instead of in the morning (when they are most commonly used), reduces death, heart attack, and stroke by more than 50%. If true, a switch to bedtime prescribing would have more impact on the health of those with high blood pressure than whether high blood pressure is treated at all.

BedMed, a community-based Canadian primary care trial, is already running and looking both to validate the findings of this Spanish study and to determine whether there might be unrecognized harms of bedtime use (such as more falls and fractures as a result of lower overnight blood pressure). One very important population that is likely to be more sensitive to the effects of medications, and almost always excluded from randomized trials, are the frail elderly (such as those who are resident in nursing homes). In order to have the greatest information about the safety and effectiveness of bedtime blood pressure medications, the BedMed team is additionally conducting a similar trial to BedMed in nursing homes ("BedMed-Frail" - the subject of this trial registration) to determine whether the risks and benefits of bedtime prescribing differ in this highly understudied population.

Basics of the trial: When patients are admitted to nursing homes, neither they nor their physicians are consulted about the timing of blood pressure medication. Unless explicitly stated to be otherwise, blood pressure pills are instead largely arbitrarily assigned for morning use by default. Given there is evidence that bedtime administration may be safer, the nursing homes participating in BedMed-Frail will have each hypertensive resident randomized to either continue with morning blood pressure medication use, as is their norm, or to have their facility's pharmacist gradually switch each residents blood pressure pills to bedtime. Over a period of roughly 3 years, health outcomes in these facilities will be tracked using routinely collected electronic health data to determine differences in things like hospitalization, death, or hip fractures - and at the end of the study the investigators hope to determine whether or not the recommendations for blood pressure medication timing in frail older adults should differ from those for the general population.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Hypertension diagnosis as indicated by ≥ 2 such billing diagnoses at any time in the administrative claims data by any provider
2. ≥ 1 once daily BP lowering medication
3. Resident in a participating long term care facility.

Exclusion Criteria:

1. Personal history of glaucoma or use of glaucoma medications. Glaucoma is an exclusion because nocturnal hypotension (i.e. excessively low blood pressure while sleeping) has been associated with ischemic optic neuropathy in such patients.
2. Any patient / family member or treating physician (all of whom will be notified in advance of the LTC facilities participation in this initiative) requesting the patient not participate.

Primary outcomes:
measure: Composite of Major Adverse Cardiovascular Events
timeFrame: 3 years (Estimate Only - study continues until 368 participants have experienced primary outcome events)
Secondary outcomes:
measure: All Cause Mortality
timeFrame: 3 years (Estimate Only - study continues until 368 participants have experienced primary outcome events)
measure: Hospitalization for Acute Coronary Syndrome / Myocardial Infarction
timeFrame: 3 years (Estimate Only - study continues until 368 participants have experienced primary outcome events)
measure: Hospitalization for Stroke
timeFrame: 3 years (Estimate Only - study continues until 368 participants have experienced primary outcome events)
measure: Hospitalization for Congestive Heart Failure
timeFrame: 3 years (Estimate Only - study continues until 368 participants have experienced primary outcome events)
measure: All Cause Unplanned Hospitalization
timeFrame: 3 years (Estimate Only - study continues until 368 participants have experienced primary outcome events)
measure: Non-vertebral Fracture
timeFrame: 3 years (Estimate Only - study continues until 368 participants have experienced primary outcome events)
measure: Number of Patients with a Fall in the Last 30 days
timeFrame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window)
measure: Number of Patients with "Deteriorated Cognition Relative to Status 90 Days Prior"
timeFrame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window)
measure: Number of Patients with Urinary Incontinence
timeFrame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window)
measure: Number of Patients with Partial or Full Thickness Decubitus Skin Ulceration ("Bed Sores")
timeFrame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window)
measure: Acute Care Costs
timeFrame: 3 years (Estimate Only - study continues until 368 participants have experienced primary outcome events)
measure: Total Cost of Care
timeFrame: 3 years (Estimate Only - study continues until 368 participants have experienced primary outcome events)
Other outcomes:
measure: Number of Participants with "Behavioural Symptoms that are Present a Minimum of 4 Days per Week and Not Easily Altered" Including a) Wandering, b) Verbal Abuse, c) Physical Abuse, d) Socially Inappropriate or Disruptive Behaviour, or e) Resisting Care
timeFrame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window)
measure: Number of Participants with Receipt (last 7 days) of Antipsychotic Medication or Physical Restraints
timeFrame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window)
measure: Receipt of Anti-Anxiety Medication on 3 or more of the Last 7 Days
timeFrame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window)
measure: Receipt of a Bedtime Sleeping Pill on 3 or More of the Last 7 Days
timeFrame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window)
measure: Number of Participants Indicated by Nursing to Have at Least One "Indicator of Depression or Anxiety" Almost Daily in the Last 30 Days
timeFrame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window)
measure: Proportion of BP Medication Doses Taken at Bedtime (Process Outcome)
timeFrame: Through study duration, up to 3 years, broken down monthly
measure: Use of at Least One Once Daily BP Medication at Bedtime (Process Outcome)
timeFrame: Through study duration, up to 3 years, broken down monthly
Locations:
city: Edmonton
country: Canada
facility: Multiple Alberta Long Term Care Facilities
state: Alberta
Study officials:
affiliation: University of Alberta
name: Scott R Garrison, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: