HypertensionPhase 4NCT02990663
The Effect of Antihypertensive Medication Timing on Morbidity and Mortality
A Phase 4 study testing Use of blood pressure lowering medication at bedtime and Use of blood pressure lowering medication in the morning in people with Hypertension, run by University of Alberta at 5 sites in Canada.
Trial summary
High blood pressure is common and its presence increases the risk of cardiovascular mortality and morbidity (most notably stroke, myocardial infarction, and congestive heart failure). Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- Use of blood pressure lowering medication at bedtime and Use of blood pressure lowering medication in the morning
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,357 participants
- Where
- 5 sitesCanada
- Study dates
- 31 Mar 2017to 22 Dec 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hypertension diagnosis as assigned by a physician or nurse practitioner
- ≥ 1 blood pressure medication taken once daily, or primary care provider willing to convert ≥ 1 blood pressure medication to once daily
- Community dwelling (i.e. not residing in a nursing home; assisted living permitted)
Who cannot join
- Palliative (as per primary care provider's judgement)
- Unable to provide informed consent (as per primary care provider's judgement)
- Personal history of glaucoma or use of glaucoma medications
- Sleep disrupting shift work (more than 3 shifts/month during participant's regular sleeping hours)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
University of Alberta
Edmonton, Alberta, T6G 2T4
University of Saskatchewan
Saskatoon, Saskatchewan, S7N 5A2
University of Toronto
Toronto, Ontario, M5S 1A1
University of British Columbia
Vancouver, British Columbia, V6T 1Z4
University of Manitoba
Winnipeg, Manitoba, R3T 2N2
About this study
Official title: The Effect of Antihypertensive Medication Timing on Morbidity and Mortality: The "BedMed" RCT
High blood pressure is common and its presence increases the risk of cardiovascular mortality and morbidity (most notably stroke, myocardial infarction, and congestive heart failure). Given blood pressure is normally higher during the day than it is overnight, blood pressure lowering medications are traditionally taken in the morning. However a randomized trial of 2156 Spanish hypertension patients published in 2010 ("MAPEC"), suggests a large (61%) reduction in mortality and cardiovascular morbidity if such medications are instead taken at bedtime. This degree of benefit far exceeds other established methods of cardiovascular risk reduction - and such a surprisingly large effect requires independent confirmation for practice to change. BedMed is a pragmatic randomized controlled trial facilitated by over 400 Canadian family physician members of the Pragmatic Trials Collaborative. During the conduct of this trial consenting hypertensive primary care patients, already established on one or more antihypertensive medications, will be randomized to either morning or bedtime antihypertensive use. Patient oriented trial outcomes evaluating both potential benefits and harms will be drawn largely from administrative health data that is routinely collected on all residents of Canada's publicly funded health care system. This trial is being conducted in 5 Canadian provinces and will continue to collect data until late 2023, at which point more than 255 primary outcome events are anticipated.
Read the detailed description
THE OPPORTUNITY BEDTIME PRESCRIBING MIGHT PROVIDE: Blood pressure normally exhibits a circadian rhythm with relatively lower pressures during sleep.(Ref 1) Lack of this sleep time "dip" correlates strongly with adverse cardiovascular events and BP correlates most strongly with such events when measured at night (i.e. during sleep).(Ref 2-5) Motivated by such observations, Spanish researchers studied the effect of taking BP medication at BEDTIME (when the effect on nighttime BP would be greatest) versus conventional morning use, when most BP medications are taken. The results of this study (the MAPEC trial) were striking.(Ref 6) Over a median 5.6 years follow-up, adverse cardiovascular events occurred in 187 of 1084 subjects taking BP medication in the morning but only 68 of 1072 subjects who took their BP medication at bedtime (relative risk 0.39, 95%CI [0.29-0.51], p < 0.001). This 61% reduction in adverse events was similar for all individual components of the primary outcome (including death from all causes, stroke, MI, new angina pectoris, CHF and retinal artery occlusions). If true, a switch to bedtime prescribing would have more impact on the health of hypertensive patients than whether high BP is treated at all. However extraordinary claims require extraordinary evidence - independent replication of such surprising findings is needed for widespread practice change to occur.
BEDMED: The BedMed trial is a pragmatic primary care trial intended to verify whether bedtime antihypertensive use, as compared to conventional morning use, reduces major adverse cardiovascular events. It is designed as an adaptive randomized registry trial within community primary care and draws both trial outcomes and baseline covariates from provincial administrative claims data (vital statistics, hospital separations, physician services, prescription dispenses, laboratory data). BedMed is government funded/facilitated, and has over 400 volunteer primary care providers recruiting participants in 5 Canadian provinces (Alberta, British Columbia, Saskatchewan, Manitoba, and Ontario). It was originally intended that the trial would continue until 406 primary outcome events were observed, however funding will expire before this occurs. As a result, BedMed will continue to recruit participants until early 2022 and complete data collection in late 2023, at which time more than 255 primary outcome events are anticipated (based on blinded observation of total events gathered at the end of 2021). The trial relies heavily on a collaboration between the volunteer family physicians of the Pragmatic Trials Collaborative (www.PragmaticTrials.ca) who will recruit for the trial and the Alberta SPOR Support Unit's Data Platform - which will facilitate accessing and analyzing the relevant administrative databases from multiple provinces (http://www.aihealthsolutions.ca/initiatives-partnerships/spor/).
DIURETIC SUB-STUDY: The "adaptive" element of the BedMed trial design refers to an interim examination of bedtime diuretic tolerance. Although it is commonly believed that diuretics can't be taken at bedtime without inducing unwanted nocturia, the sparse evidence in the literature suggests this may not be the case.(Ref 7,8) Rather than excluding patients whose only medication is a diuretic the investigators will instead initially include such patients and evaluate bedtime diuretic tolerance early on in the trial to determine whether or not such patients should continue to be enrolled. Specifically, upon allocating to bedtime dosing 203 patients whose only BP medication is an AM diuretic, the investigators will analyze 6-week compliance to bedtime allocation for all participants with a single morning BP medication (of all types). If diuretic compliance is worse, the "adaptive" trial design will exclude enrolment of additional patients whose only BP medication is a diuretic. The BedMed investigators will report on bedtime diuretic tolerance separate from (and in advance of) the main BedMed analysis.
INTERIM SAFETY ANALYSIS: An independent data safety monitoring board (DSMB) organized and chaired by Jim Wright (Cochrane Hypertension Review Group Coordinating Editor) is expected to review all data in March 2022, at which time approximately 150-160 primary outcome events are expected. 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 DSMB will apply clinical judgement and make recommendations to the steering committee on whether the trial should stop early.
- Conditions
- Hypertension
- Being tested
- Use of blood pressure lowering medication at bedtime, Use of blood pressure lowering medication in the morning
- Keywords
- Pragmatic, Primary Care, Chronotherapy, Administrative Data, Stroke, Myocardial Infarction, Congestive Heart Failure, Glaucoma, Dementia, Hip Fracture
- Medical subject headings
- Hypertension, Stroke, Myocardial Infarction, Heart Failure, Glaucoma, Dementia, Hip Fractures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Use of blood pressure lowering medication at bedtimeOther
Blood pressure lowering medications will be switched (one at a time as tolerated) to bedtime, or maintained at bedtime if already taken at that time. All decisions related to which, and how many, medications to switch are at the discretion of the care provider.
Use of blood pressure lowering medication in the morningOther
Blood pressure lowering medications will be switched (one at a time as tolerated) to morning, or maintained in the morning if already taken at that time. All decisions related to which, and how many, medications to switch are at the discretion of the care provider.
| Study group | Role | What they receive |
|---|---|---|
| Bedtime BP Meds | Experimental | Use of blood pressure lowering medication at bedtime Receives: Other: Use of blood pressure lowering medication at bedtime |
| Morning BP Meds | Active comparator | Use of blood pressure lowering medication in the morning Receives: Other: Use of blood pressure lowering medication in the morning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Adverse Cardiovascular Events
First occurrence of either death (all-cause), or hospitalization or emergency department visit for acute coronary syndrome / MI, congestive heart failure, or stroke.
Measured: Through study completion, an average of 4 years
Secondary outcomes (9)
All-cause mortality
Death from any cause.
Measured: Through study completion, an average of 4 years
Acute coronary syndrome
Hospitalization or ER visit for acute coronary syndrome or MI.
Measured: Through study completion, an average of 4 years
CHF Hospitalization
Hospitalization or ER visit for congestive heart failure.
Measured: Through study completion, an average of 4 years
Stoke
Hospitalization or ER visit for stroke (excludes TIA).
Measured: Through study completion, an average of 4 years
All-cause hospitalization
Hospitalization or ER visit for any cause
Measured: Through study completion, an average of 4 years
Long term care admission
Newly admitted to a nursing home or assisted living facility as primary residence
Measured: Through study completion, an average of 4 years
New glaucoma diagnosis
First-ever glaucoma diagnosis
Measured: Through study completion, an average of 4 years
Non-vertebral fracture
Fracture of any bone other than the vertebra of the back or neck
Measured: Through study completion, an average of 4 years
Cognitive decline
Cognitive performance worsening by 2 or more points compared to baseline, as measured by the Short Blessed Test
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2016 (estimated)
- Study start31 Mar 2017
- Primary completion22 Dec 2023
- Study completion22 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 3,357 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Alberta Innovates Health Solutions, Alberta Health services, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Scott R Garrison, MD, PhD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02990663
- Sponsor's protocol ID
- BedMed Nov 30 2016
- Status last verified
- Aug 2024
- First submitted
- 5 Dec 2016
- Last updated
- 27 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon completion of all planned studies related to this project, anonymized patient level data for all outcomes and baseline characteristics will be made available in the form of a downloadable spreadsheet accessed through the Pragmatic Trials Collaborative's website (www.PragmaticTrials.ca)
Publications
Veerman DP, Imholz BP, Wieling W, Wesseling KH, van Montfrans GA. Circadian profile of systemic hemodynamics. Hypertension. 1995 Jul;26(1):55-9. doi: 10.1161/01.hyp.26.1.55.
PubMed 7607733Clement DL, De Buyzere ML, De Bacquer DA, de Leeuw PW, Duprez DA, Fagard RH, Gheeraert PJ, Missault LH, Braun JJ, Six RO, Van Der Niepen P, O'Brien E; Office versus Ambulatory Pressure Study Investigators. Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Engl J Med. 2003 Jun 12;348(24):2407-15. doi: 10.1056/NEJMoa022273.
PubMed 12802026Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A, Santucci C, Reboldi G, et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension. 1994 Dec;24(6):793-801. doi: 10.1161/01.hyp.24.6.793.
PubMed 7995639Ben-Dov IZ, Kark JD, Ben-Ishay D, Mekler J, Ben-Arie L, Bursztyn M. Predictors of all-cause mortality in clinical ambulatory monitoring: unique aspects of blood pressure during sleep. Hypertension. 2007 Jun;49(6):1235-41. doi: 10.1161/HYPERTENSIONAHA.107.087262. Epub 2007 Mar 26.
PubMed 17389258Fagard RH, Celis H, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008 Jan;51(1):55-61. doi: 10.1161/HYPERTENSIONAHA.107.100727. Epub 2007 Nov 26.
PubMed 18039980Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010 Sep;27(8):1629-51. doi: 10.3109/07420528.2010.510230.
PubMed 20854139Rembratt A, Norgaard JP, Andersson KE. Nocturia and associated morbidity in a community-dwelling elderly population. BJU Int. 2003 Nov;92(7):726-30. doi: 10.1046/j.1464-410x.2003.04467.x.
PubMed 14616455Asplund R. Nocturia in relation to sleep, health, and medical treatment in the elderly. BJU Int. 2005 Sep;96 Suppl 1:15-21. doi: 10.1111/j.1464-410X.2005.05653.x.
PubMed 16083452Garrison SR, Bakal JA, Kolber MR, Korownyk CS, Green LA, Kirkwood JEM, McAlister FA, Padwal RS, Lewanczuk R, Hill MD, Singer AG, Katz A, Kelmer MD, Gayayan A, Campbell FN, Vucenovic A, Archibald NR, Yeung JMS, Youngson ERE, McGrail K, O'Neill BG, Greiver M, Manca DP, Kraut RY, Wang T, Manns BJ, Mangin DA, MacLean C, McCormack J, Wong ST, Norris C, Allan GM. Antihypertensive Medication Timing and Cardiovascular Events and Death: The BedMed Randomized Clinical Trial. JAMA. 2025 Jun 17;333(23):2061-2072. doi: 10.1001/jama.2025.4390.
PubMed 40354045Garrison SR, Kelmer M, Korownyk T, Kolber MR, Allan GM, Bakal J, Singer A, Katz A, Mcalister F, Padwal RS, Lewanczuk R, Hill MD, McGrail K, O'Neill B, Greiver M, Manca DP, Mangin D, Wong ST, Kirkwood JEM, McCormack JP, Yeung JMS, Green L. Tolerability of bedtime diuretics: a prospective cohort analysis. BMJ Open. 2023 Jun 6;13(6):e068188. doi: 10.1136/bmjopen-2022-068188.
PubMed 37280022Garrison SR, Kolber MR, Allan GM, Bakal J, Green L, Singer A, Trueman DR, McAlister FA, Padwal RS, Hill MD, Manns B, McGrail K, O'Neill B, Greiver M, Froentjes LS, Manca DP, Mangin D, Wong ST, MacLean C, Kirkwood JE, McCracken R, McCormack JP, Norris C, Korownyk T. Bedtime versus morning use of antihypertensives for cardiovascular risk reduction (BedMed): protocol for a prospective, randomised, open-label, blinded end-point pragmatic trial. BMJ Open. 2022 Feb 24;12(2):e059711. doi: 10.1136/bmjopen-2021-059711.
PubMed 35210352
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Antihypertensive Medication Timing on Morbidity and Mortality: The "BedMed" RCT
- ClinicalTrials.gov ID
- NCT02990663
- Acronym / sponsor ID
- BedMed Nov 30 2016
- Conditions
- Hypertension
- Keywords
- Pragmatic, Primary Care, Chronotherapy, Administrative Data, Stroke, Myocardial Infarction, Congestive Heart Failure, Glaucoma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,357 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Alberta Innovates Health Solutions, Alberta Health services, Canadian Institutes of Health Research (CIHR)
- Study start
- 31 Mar 2017 (actual)
- Primary completion
- 22 Dec 2023 (actual)
- Study completion
- 22 Dec 2023 (actual)
- First posted
- 13 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
High blood pressure is common and its presence increases the risk of cardiovascular mortality and morbidity (most notably stroke, myocardial infarction, and congestive heart failure). Given blood pressure is normally higher during the day than it is overnight, blood pressure lowering medications are traditionally taken in the morning. However a randomized trial of 2156 Spanish hypertension patients published in 2010 ("MAPEC"), suggests a large (61%) reduction in mortality and cardiovascular morbidity if such medications are instead taken at bedtime. This degree of benefit far exceeds other established methods of cardiovascular risk reduction - and such a surprisingly large effect requires independent confirmation for practice to change. BedMed is a pragmatic randomized controlled trial facilitated by over 400 Canadian family physician members of the Pragmatic Trials Collaborative. During the conduct of this trial consenting hypertensive primary care patients, already established on one or more antihypertensive medications, will be randomized to either morning or bedtime antihypertensive use. Patient oriented trial outcomes evaluating both potential benefits and harms will be drawn largely from administrative health data that is routinely collected on all residents of Canada's publicly funded health care system. This trial is being conducted in 5 Canadian provinces and will continue to collect data until late 2023, at which point more than 255 primary outcome events are anticipated.
Detailed description
THE OPPORTUNITY BEDTIME PRESCRIBING MIGHT PROVIDE: Blood pressure normally exhibits a circadian rhythm with relatively lower pressures during sleep.(Ref 1) Lack of this sleep time "dip" correlates strongly with adverse cardiovascular events and BP correlates most strongly with such events when measured at night (i.e. during sleep).(Ref 2-5) Motivated by such observations, Spanish researchers studied the effect of taking BP medication at BEDTIME (when the effect on nighttime BP would be greatest) versus conventional morning use, when most BP medications are taken. The results of this study (the MAPEC trial) were striking.(Ref 6) Over a median 5.6 years follow-up, adverse cardiovascular events occurred in 187 of 1084 subjects taking BP medication in the morning but only 68 of 1072 subjects who took their BP medication at bedtime (relative risk 0.39, 95%CI [0.29-0.51], p < 0.001). This 61% reduction in adverse events was similar for all individual components of the primary outcome (including death from all causes, stroke, MI, new angina pectoris, CHF and retinal artery occlusions). If true, a switch to bedtime prescribing would have more impact on the health of hypertensive patients than whether high BP is treated at all. However extraordinary claims require extraordinary evidence - independent replication of such surprising findings is needed for widespread practice change to occur.
BEDMED: The BedMed trial is a pragmatic primary care trial intended to verify whether bedtime antihypertensive use, as compared to conventional morning use, reduces major adverse cardiovascular events. It is designed as an adaptive randomized registry trial within community primary care and draws both trial outcomes and baseline covariates from provincial administrative claims data (vital statistics, hospital separations, physician services, prescription dispenses, laboratory data). BedMed is government funded/facilitated, and has over 400 volunteer primary care providers recruiting participants in 5 Canadian provinces (Alberta, British Columbia, Saskatchewan, Manitoba, and Ontario). It was originally intended that the trial would continue until 406 primary outcome events were observed, however funding will expire before this occurs. As a result, BedMed will continue to recruit participants until early 2022 and complete data collection in late 2023, at which time more than 255 primary outcome events are anticipated (based on blinded observation of total events gathered at the end of 2021). The trial relies heavily on a collaboration between the volunteer family physicians of the Pragmatic Trials Collaborative (www.PragmaticTrials.ca) who will recruit for the trial and the Alberta SPOR Support Unit's Data Platform - which will facilitate accessing and analyzing the relevant administrative databases from multiple provinces (http://www.aihealthsolutions.ca/initiatives-partnerships/spor/).
DIURETIC SUB-STUDY: The "adaptive" element of the BedMed trial design refers to an interim examination of bedtime diuretic tolerance. Although it is commonly believed that diuretics can't be taken at bedtime without inducing unwanted nocturia, the sparse evidence in the literature suggests this may not be the case.(Ref 7,8) Rather than excluding patients whose only medication is a diuretic the investigators will instead initially include such patients and evaluate bedtime diuretic tolerance early on in the trial to determine whether or not such patients should continue to be enrolled. Specifically, upon allocating to bedtime dosing 203 patients whose only BP medication is an AM diuretic, the investigators will analyze 6-week compliance to bedtime allocation for all participants with a single morning BP medication (of all types). If diuretic compliance is worse, the "adaptive" trial design will exclude enrolment of additional patients whose only BP medication is a diuretic. The BedMed investigators will report on bedtime diuretic tolerance separate from (and in advance of) the main BedMed analysis.
INTERIM SAFETY ANALYSIS: An independent data safety monitoring board (DSMB) organized and chaired by Jim Wright (Cochrane Hypertension Review Group Coordinating Editor) is expected to review all data in March 2022, at which time approximately 150-160 primary outcome events are expected. 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 DSMB will apply clinical judgement and make recommendations to the steering committee on whether the trial should stop early.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bedtime BP Meds | Experimental | Other: Use of blood pressure lowering medication at bedtimeUse of blood pressure lowering medication at bedtime |
| Morning BP Meds | Active comparator | Other: Use of blood pressure lowering medication in the morningUse of blood pressure lowering medication in the morning |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Hypertension diagnosis as assigned by a physician or nurse practitioner
- ≥ 1 blood pressure medication taken once daily, or primary care provider willing to convert ≥ 1 blood pressure medication to once daily
- Community dwelling (i.e. not residing in a nursing home; assisted living permitted)
Key exclusion criteria (4 listed)
- Palliative (as per primary care provider's judgement)
- Unable to provide informed consent (as per primary care provider's judgement)
- Personal history of glaucoma or use of glaucoma medications
- Sleep disrupting shift work (more than 3 shifts/month during participant's regular sleeping hours)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Use of blood pressure lowering medication at bedtimeBlood pressure lowering medications will be switched (one at a time as tolerated) to bedtime, or maintained at bedtime if already taken at that time. All decisions related to which, and how many, medications to switch are at the discretion of the care provider. | Other | Bedtime BP Meds |
| Use of blood pressure lowering medication in the morningBlood pressure lowering medications will be switched (one at a time as tolerated) to morning, or maintained in the morning if already taken at that time. All decisions related to which, and how many, medications to switch are at the discretion of the care provider. | Other | Morning BP Meds |
Primary outcome
Major Adverse Cardiovascular Events
Time frame: Through study completion, an average of 4 years
First occurrence of either death (all-cause), or hospitalization or emergency department visit for acute coronary syndrome / MI, congestive heart failure, or stroke.
9 secondary outcomes
All-cause mortality
Time frame: Through study completion, an average of 4 years
Acute coronary syndrome
Time frame: Through study completion, an average of 4 years
CHF Hospitalization
Time frame: Through study completion, an average of 4 years
Stoke
Time frame: Through study completion, an average of 4 years
All-cause hospitalization
Time frame: Through study completion, an average of 4 years
Long term care admission
Time frame: Through study completion, an average of 4 years
New glaucoma diagnosis
Time frame: Through study completion, an average of 4 years
Non-vertebral fracture
Time frame: Through study completion, an average of 4 years
Cognitive decline
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
- Background: PubMed 7607733Veerman DP, Imholz BP, Wieling W, Wesseling KH, van Montfrans GA. Circadian profile of systemic hemodynamics. Hypertension. 1995 Jul;26(1):55-9. doi: 10.1161/01.hyp.26.1.55.
- Background: PubMed 12802026Clement DL, De Buyzere ML, De Bacquer DA, de Leeuw PW, Duprez DA, Fagard RH, Gheeraert PJ, Missault LH, Braun JJ, Six RO, Van Der Niepen P, O'Brien E; Office versus Ambulatory Pressure Study Investigators. Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Engl J Med. 2003 Jun 12;348(24):2407-15. doi: 10.1056/NEJMoa022273.
- Background: PubMed 7995639Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A, Santucci C, Reboldi G, et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension. 1994 Dec;24(6):793-801. doi: 10.1161/01.hyp.24.6.793.
- Background: PubMed 17389258Ben-Dov IZ, Kark JD, Ben-Ishay D, Mekler J, Ben-Arie L, Bursztyn M. Predictors of all-cause mortality in clinical ambulatory monitoring: unique aspects of blood pressure during sleep. Hypertension. 2007 Jun;49(6):1235-41. doi: 10.1161/HYPERTENSIONAHA.107.087262. Epub 2007 Mar 26.
- Background: PubMed 18039980Fagard RH, Celis H, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008 Jan;51(1):55-61. doi: 10.1161/HYPERTENSIONAHA.107.100727. Epub 2007 Nov 26.
- Background: PubMed 20854139Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010 Sep;27(8):1629-51. doi: 10.3109/07420528.2010.510230.
- Background: PubMed 14616455Rembratt A, Norgaard JP, Andersson KE. Nocturia and associated morbidity in a community-dwelling elderly population. BJU Int. 2003 Nov;92(7):726-30. doi: 10.1046/j.1464-410x.2003.04467.x.
- Background: PubMed 16083452Asplund R. Nocturia in relation to sleep, health, and medical treatment in the elderly. BJU Int. 2005 Sep;96 Suppl 1:15-21. doi: 10.1111/j.1464-410X.2005.05653.x.
- Derived from this study: PubMed 40354045Garrison SR, Bakal JA, Kolber MR, Korownyk CS, Green LA, Kirkwood JEM, McAlister FA, Padwal RS, Lewanczuk R, Hill MD, Singer AG, Katz A, Kelmer MD, Gayayan A, Campbell FN, Vucenovic A, Archibald NR, Yeung JMS, Youngson ERE, McGrail K, O'Neill BG, Greiver M, Manca DP, Kraut RY, Wang T, Manns BJ, Mangin DA, MacLean C, McCormack J, Wong ST, Norris C, Allan GM. Antihypertensive Medication Timing and Cardiovascular Events and Death: The BedMed Randomized Clinical Trial. JAMA. 2025 Jun 17;333(23):2061-2072. doi: 10.1001/jama.2025.4390.
- Derived from this study: PubMed 37280022Garrison SR, Kelmer M, Korownyk T, Kolber MR, Allan GM, Bakal J, Singer A, Katz A, Mcalister F, Padwal RS, Lewanczuk R, Hill MD, McGrail K, O'Neill B, Greiver M, Manca DP, Mangin D, Wong ST, Kirkwood JEM, McCormack JP, Yeung JMS, Green L. Tolerability of bedtime diuretics: a prospective cohort analysis. BMJ Open. 2023 Jun 6;13(6):e068188. doi: 10.1136/bmjopen-2022-068188.
- Derived from this study: PubMed 35210352Garrison SR, Kolber MR, Allan GM, Bakal J, Green L, Singer A, Trueman DR, McAlister FA, Padwal RS, Hill MD, Manns B, McGrail K, O'Neill B, Greiver M, Froentjes LS, Manca DP, Mangin D, Wong ST, MacLean C, Kirkwood JE, McCracken R, McCormack JP, Norris C, Korownyk T. Bedtime versus morning use of antihypertensives for cardiovascular risk reduction (BedMed): protocol for a prospective, randomised, open-label, blinded end-point pragmatic trial. BMJ Open. 2022 Feb 24;12(2):e059711. doi: 10.1136/bmjopen-2021-059711.
- The Pragmatic Trials CollaborativeLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Upon completion of all planned studies related to this project, anonymized patient level data for all outcomes and baseline characteristics will be made available in the form of a downloadable spreadsheet accessed through the Pragmatic Trials Collaborative's website (www.PragmaticTrials.ca)
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Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott R Garrison, MD, PhD principal investigator
University of Alberta
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Use of blood pressure lowering medication at bedtime and Use of blood pressure lowering medication in the morning in people with Hypertension, run by University of Alberta at 5 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Adverse Cardiovascular Events (time frame: Through study completion, an average of 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02990663, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2024.