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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04054648
Recruitment Status : Enrolling by invitation
First Posted : August 13, 2019
Last Update Posted : March 10, 2022
Sponsor:
Collaborators:
Alberta Innovates Health Solutions
Canadian Institutes of Health Research (CIHR)
EnACt
Alberta Health services
Information provided by (Responsible Party):
Scott Garrison, University of Alberta

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 2 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.


Condition or disease Intervention/treatment Phase
Hypertension Dementia Other: Bedtime administration of the participant's pre-existing antihypertensive medications Not Applicable

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. The trial will end upon 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. The investigators will report the behavioural outcomes as a secondary analysis, in a separate publication, with the primary outcome for that secondary analysis being an MDS record by the care team that problem behaviours are present a minimum of 4 days per week and not easily altered (see detailed description below).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 775 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Event-driven Prospective Randomized Open Blinded End-Point (PROBE) Randomized Trial.
Masking: Single (Outcomes Assessor)
Masking Description: Outcomes are drawn from administrative claims data which derive from hospital separations (diagnoses and procedures) and physician billings. The acute care providers submitting the billings which define our outcomes will typically be meeting the patient for the first time, unaware of the patient's participation in BedMed-Frail, and unaware of the facility's administration time for once daily antihypertensives.
Primary Purpose: Prevention
Official Title: Does the Potential Benefit of Bedtime Antihypertensive Prescribing Extend to Frail Populations? The "BedMed-Frail" Randomized Controlled Trial
Actual Study Start Date : May 14, 2020
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Bedtime Antihypertensive Medications
The LTC facility's pharmacist will switch all once daily antihypertensive medications, one at a time as tolerated, to bedtime. Blood pressure lowering medications taken more than once per day are left alone.
Other: Bedtime administration of the participant's pre-existing antihypertensive medications
Changing the administration time of once daily blood pressure lowering medications, one at a time as tolerated, from morning to bedtime.

No Intervention: Morning Antihypertensive Medications
No change to blood pressure medication timing is made. By default, most patients are using once daily antihypertensive medications in the morning at baseline.



Primary Outcome Measures :
  1. Composite of Major Adverse Cardiovascular Events [ Time Frame: 2 years (Estimate Only - study continues until 368 participants have experienced primary outcome events) ]
    Composite of all-cause death and hospital admission or emergency room visit for acute coronary syndrome / myocardial infarction, heart failure, or stroke - as recorded in governmental health claims databases


Secondary Outcome Measures :
  1. All Cause Mortality [ Time Frame: 2 years (Estimate Only - study continues until 368 participants have experienced primary outcome events) ]
    All cause death - as recorded in governmental health claims databases

  2. Hospitalization for Acute Coronary Syndrome / Myocardial Infarction [ Time Frame: 2 years (Estimate Only - study continues until 368 participants have experienced primary outcome events) ]
    Hospitalization or Emergency Room Visit for Acute Coronary Syndrome / Myocardial Infarction - as recorded in governmental health claims databases

  3. Hospitalization for Stroke [ Time Frame: 2 years (Estimate Only - study continues until 368 participants have experienced primary outcome events) ]
    Hospitalization or Emergency Room Visit for Stroke - as recorded in governmental health claims databases

  4. Hospitalization for Congestive Heart Failure [ Time Frame: 2 years (Estimate Only - study continues until 368 participants have experienced primary outcome events) ]
    Hospitalization or Emergency Room Visit for Congestive Heart Failure - as recorded in governmental health claims databases

  5. All Cause hospitalization [ Time Frame: 2 years (Estimate Only - study continues until 368 participants have experienced primary outcome events) ]
    Hospitalization or Emergency Room Visit for Any Reason - as recorded in governmental health claims databases

  6. Acute Care Costs [ Time Frame: 2 years (Estimate Only - study continues until 368 participants have experienced primary outcome events) ]
    Calculated from all hospitalizations using the resource intensity weight (RIW) and length of stay (LOS) as recorded in governmental administrative claims data

  7. Fracture [ Time Frame: 2 years (Estimate Only - study continues until 368 participants have experienced primary outcome events) ]
    Any Physician Billing (Hospital or Community) for a Long Bone (humerus/radius/ulna/femur/tibia), Pelvic, Patellar, Scapular, Skull, Jaw, or Rib Fracture (i.e. All fractures excluding vertebrae and small bones of the hands and feet, for which falling is often not the mechanism of injury)

  8. Number of Patients with a Fall in the Last 30 days [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization

  9. Number of Patients with "Deteriorated Cognition Relative to Status 90 Days Prior" [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization

  10. Number of Patients with Urinary Continence [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization

  11. Number of Patients with Full Thickness Skin Ulceration (Stage 3 or 4) [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization


Other Outcome Measures:
  1. 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 [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization. This will be the primary outcome for the secondary exploration (to be published separately) of the effect of BP medication timing on behaviour.

  2. Number of Participants with Receipt (last 7 days) of Antipsychotic Medication or Physical Restraints [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization. Physical restraints include trunk restraints, limb restraints, or a chair that prevents rising, but does not include bedrails.This will be part of the secondary exploration examining the effects of BP medication timing on behaviour.

  3. Number of Participants with Receipt (last 7 days) of Physical Restraints [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization. Physical restraints include trunk restraints, limb restraints, or a chair that prevents rising, but does not include bedrails. This will be part of the secondary exploration examining the effects of BP medication timing on behaviour.

  4. Number of Participants with Receipt (last 7 days) of Antipsychotic Medication [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization. This will be part of the secondary exploration examining the effects of BP medication timing on behaviour.

  5. Number of Days per Week (last 7 days) Anti-Anxiety Medication is Used Among Those Who Use it Less Than Daily (i.e. among those who use it as needed, and not regularly) [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization.This will be part of the secondary exploration examining the effects of BP medication timing on behaviour.

  6. Number of Days per Week (last 7 days) Hypnotic (Bedtime Sleeping Pill) Medication is Used Among Those Who Use it Less Than Daily (i.e. among those who use it as needed, and not regularly) [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization. This will be part of the secondary exploration examining the effects of BP medication timing on behaviour.

  7. Number of Participants Indicated by Nursing to have "Indicators of Depression or Anxiety Almost Daily in last 30 days" [ Time Frame: 4.5 Months (Average - will occur within a 3 to 6 month post randomization window) ]
    As recorded by a nurse checking a single tick box in the First Quarterly Minimum Data Set (MDS) Report Recorded at the Care Facility in the 3 to 6 Month Window Following Randomization.This will be part of the secondary exploration examining the effects of BP medication timing on behaviour.

  8. Percentage of Once Daily Blood Pressure Medications Taken According to Allocation (Process Outcome) [ Time Frame: 6 months ]
    Obtained by Hand Audit of Medication Records 6 months Post Date of Randomization

  9. Number of Once Daily Blood Pressure Medications in Use 6 Months Post Randomization (Process Outcome) [ Time Frame: 6 months ]
    As recorded in governmental health claims database tracking pharmaceutical dispensing

  10. Number of Blood Pressure Medications Used More than Once Daily 6 Months Post Randomization (Process Outcome) [ Time Frame: 6 months ]
    As recorded in governmental health claims database tracking pharmaceutical dispensing



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 of the LTC facilities participation in this initiative) requesting the patient not participate.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04054648


Locations
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Canada, Alberta
Multiple Alberta Long Term Care Facilities
Edmonton, Alberta, Canada
Sponsors and Collaborators
University of Alberta
Alberta Innovates Health Solutions
Canadian Institutes of Health Research (CIHR)
EnACt
Alberta Health services
Investigators
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Principal Investigator: Scott R Garrison, MD, PhD University of Alberta
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Responsible Party: Scott Garrison, Professor, University of Alberta
ClinicalTrials.gov Identifier: NCT04054648    
Other Study ID Numbers: Pro00086129
First Posted: August 13, 2019    Key Record Dates
Last Update Posted: March 10, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Upon publication of all trial results, de-identified patient level data will be posted in spreadsheet format on the website of the Pragmatic Trials Collaborative (www.PragmaticTrials.ca) for general public access.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data will be posted co-incident with the final planned publication and intended for long-term availability.
Access Criteria: The data will be downloadable in the form of an Excel spreadsheet for anyone who wishes to access it. No application process will be necessary.
URL: http://PragmaticTrials.ca

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Scott Garrison, University of Alberta:
Pragmatic
Primary Care
Chronotherapy
Administrative Data
Behaviourism
Sundowning
Stroke
Myocardial Infarction
Heart Failure
Hip Fracture
Nursing Home
Long Term Care
Additional relevant MeSH terms:
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Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Antihypertensive Agents