HypertensionPhase 4HARMONYNCT01669928
Anti-hypertensive Medication Dosing Regimen in Effective Blood Pressure Control
A Phase 4 study testing Anti-hypertensive Medication - in people with Hypertension, run by Imperial College London at 2 sites in 2 countries.
Trial summary
A randomised crossover trial of anti-hypertensive medication dosing regimen in effective blood pressure control. To investigate whether there is a difference in 24 hour blood pressure (BP) control when antihypertensive medications are taken in the morning compared with the evening. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Anti-hypertensive Medication -
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Apr 2012to Jul 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Caucasian patients aged 18-80 years;
- History of any grade of hypertension for at least 1 year, including at least 3 months of constant antihypertensive medication (consisting of ≥ 1 antihypertensive drugs, each administered in one dose daily), with reasonably controlled BP (≤150/90 mmHg and ≥ 115/75 mmHg on usual medication) based on previous clinic records, in the last 3 months.
Who cannot join
- BP levels > 150/90 mmHg or < 115/75 mmHg in the last 3 months.
- Postural hypotension, defined as symptoms resulting from a > 20 mm Hg drop of systolic BP or a > 10 mm Hg drop of diastolic BP or both between 1 and 3 min after standing from the sitting position.
- Known Extreme dippers at baseline (fall of mean night time SBP > 20% of mean day time SBP)
- Individuals with jobs which require night-time shift work.
- Pregnant women or those planning to become pregnant.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Hellenic Anglo Research Into Morning Or Evening Antihypertensive Drug deliverY Trial
A randomised crossover trial of anti-hypertensive medication dosing regimen in effective blood pressure control.
To investigate whether there is a difference in 24 hour blood pressure (BP) control when antihypertensive medications are taken in the morning compared with the evening.
Read the detailed description
The identification of any significant difference could lead to more effective therapeutic management of arterial hypertension, which in turn would result in a reduced cardiovascular burden, lower costs and a better quality of life for hypertensive patients.
- Conditions
- Hypertension
- Being tested
- Anti-hypertensive Medication -
- Keywords
- Hypertension
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-hypertensive Medication -Drug
Also called PR1 Diruetics, PR3 Beta Blockers, PR4 Calcium channel blockers, PR5 ACE inhibitors
Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication.
Dosing regimen either in the morning (between 06.00 and 11.00) or in the evening (between 18.00 and 23.00).
| Study group | Role | What they receive |
|---|---|---|
| Evening medication | Active comparator | Anti hypertensive medication in the evening (between 18.00 and 23.00) Receives: Drug: Anti-hypertensive Medication - |
| Morning medication | Active comparator | Antihypertensive medication in the morning(between 06.00 and 11.00) Receives: Drug: Anti-hypertensive Medication - |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in 24 Hour Systolic Blood Pressure
Changes in 24 hour systolic Blood Pressure using ABPM
Measured: 6 months
Secondary outcomes (8)
Mean Day-time ABPM Systolic BP
Measured: 6 months
Mean Day-time ABPM Diastolic BP
Measured: 6 months
Μean Night Time ABPM Systolic BP
Measured: 6 months
Μean Night Time ABPM Diastolic BP
Measured: 6 months
Mean Clinic - Systolic BP
This measure was assessed at a clinic.
Measured: 6 months
Mean Clinic - Diastolic BP
This measure was assessed at a clinic.
Measured: 6 months
Self Reported Side Effects
Serious Adverse Events reported during the trial
Measured: 12 months
Quality of Life Score
Quality of Life Score via questionnaire - EQ-5D-5L Score scale is 0-100, 100 optimal health state.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2012 (estimated)
- Study startApr 2012
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Aristotle University Of Thessaloniki
- Responsible party
- Sponsor
- Investigators
- Neil Poulter, MRCS LRCP MBBS MRCP MSc FRCP, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01669928
- Sponsor's protocol ID
- CRO1749
- Acronym
- HARMONY
- Status last verified
- Mar 2021
- First submitted
- 2 Jul 2012
- Last updated
- 8 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lemmer B. Clinical chronopharmacology: the importance of time in drug treatment. Ciba Found Symp. 1995;183:235-47; discussion 247-53. doi: 10.1002/9780470514597.ch13.
PubMed 7656688Bruguerolle B. Chronopharmacokinetics. Current status. Clin Pharmacokinet. 1998 Aug;35(2):83-94. doi: 10.2165/00003088-199835020-00001.
PubMed 9739478Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010 Mar 13;375(9718):895-905. doi: 10.1016/S0140-6736(10)60308-X.
PubMed 20226988Smolensky MH, Hermida RC, Ayala DE, Tiseo R, Portaluppi F. Administration-time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension. Blood Press Monit. 2010 Aug;15(4):173-80. doi: 10.1097/MBP.0b013e32833c7308.
PubMed 20571367Hermida 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 20854139Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301.
PubMed 10639539Mayet J, Chapman N, Li CK, Shahi M, Poulter NR, Sever PS, Foale RA, Thom SA. Ethnic differences in the hypertensive heart and 24-hour blood pressure profile. Hypertension. 1998 May;31(5):1190-4. doi: 10.1161/01.hyp.31.5.1190.
PubMed 9576134Poulter NR, Savopoulos C, Anjum A, Apostolopoulou M, Chapman N, Cross M, Falaschetti E, Fotiadis S, James RM, Kanellos I, Szigeti M, Thom S, Sever P, Thompson D, Hatzitolios AI. Randomized Crossover Trial of the Impact of Morning or Evening Dosing of Antihypertensive Agents on 24-Hour Ambulatory Blood Pressure. Hypertension. 2018 Oct;72(4):870-873. doi: 10.1161/HYPERTENSIONAHA.118.11101.
PubMed 30354703
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hellenic Anglo Research Into Morning Or Evening Antihypertensive Drug deliverY Trial
- ClinicalTrials.gov ID
- NCT01669928
- Acronym / sponsor ID
- HARMONY / CRO1749
- Conditions
- Hypertension
- Keywords
- Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Aristotle University Of Thessaloniki
- Study start
- Apr 2012 (actual)
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 21 Aug 2012 (estimated)
- Results
- Posted 8 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomised crossover trial of anti-hypertensive medication dosing regimen in effective blood pressure control.
To investigate whether there is a difference in 24 hour blood pressure (BP) control when antihypertensive medications are taken in the morning compared with the evening.
Detailed description
The identification of any significant difference could lead to more effective therapeutic management of arterial hypertension, which in turn would result in a reduced cardiovascular burden, lower costs and a better quality of life for hypertensive patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Evening medication | Active comparator | Drug: Anti-hypertensive Medication -Anti hypertensive medication in the evening (between 18.00 and 23.00) |
| Morning medication | Active comparator | Drug: Anti-hypertensive Medication -Antihypertensive medication in the morning(between 06.00 and 11.00) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Caucasian patients aged 18-80 years;
- History of any grade of hypertension for at least 1 year, including at least 3 months of constant antihypertensive medication (consisting of ≥ 1 antihypertensive drugs, each administered in one dose daily), with reasonably controlled BP (≤150/90 mmHg and ≥ 115/75 mmHg on usual medication) based on previous clinic records, in the last 3 months.
Key exclusion criteria (5 listed)
- BP levels > 150/90 mmHg or < 115/75 mmHg in the last 3 months.
- Postural hypotension, defined as symptoms resulting from a > 20 mm Hg drop of systolic BP or a > 10 mm Hg drop of diastolic BP or both between 1 and 3 min after standing from the sitting position.
- Known Extreme dippers at baseline (fall of mean night time SBP > 20% of mean day time SBP)
- Individuals with jobs which require night-time shift work.
- Pregnant women or those planning to become pregnant.
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 |
|---|---|---|
| Anti-hypertensive Medication -Also: PR1 Diruetics, PR3 Beta Blockers, PR4 Calcium channel blockers, PR5 ACE inhibitorsPatients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication. Dosing regimen either in the morning (between 06.00 and 11.00) or in the evening (between 18.00 and 23.00). | Drug | Evening medication, Morning medication |
Primary outcome
Changes in 24 Hour Systolic Blood Pressure
Time frame: 6 months
Changes in 24 hour systolic Blood Pressure using ABPM
8 secondary outcomes
Mean Day-time ABPM Systolic BP
Time frame: 6 months
Mean Day-time ABPM Diastolic BP
Time frame: 6 months
Μean Night Time ABPM Systolic BP
Time frame: 6 months
Μean Night Time ABPM Diastolic BP
Time frame: 6 months
Mean Clinic - Systolic BP
Time frame: 6 months
Mean Clinic - Diastolic BP
Time frame: 6 months
Self Reported Side Effects
Time frame: 12 months
Quality of Life Score
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7656688Lemmer B. Clinical chronopharmacology: the importance of time in drug treatment. Ciba Found Symp. 1995;183:235-47; discussion 247-53. doi: 10.1002/9780470514597.ch13.
- Background: PubMed 9739478Bruguerolle B. Chronopharmacokinetics. Current status. Clin Pharmacokinet. 1998 Aug;35(2):83-94. doi: 10.2165/00003088-199835020-00001.
- Background: PubMed 20226988Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010 Mar 13;375(9718):895-905. doi: 10.1016/S0140-6736(10)60308-X.
- Background: PubMed 20571367Smolensky MH, Hermida RC, Ayala DE, Tiseo R, Portaluppi F. Administration-time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension. Blood Press Monit. 2010 Aug;15(4):173-80. doi: 10.1097/MBP.0b013e32833c7308.
- 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 10639539Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301.
- Background: PubMed 9576134Mayet J, Chapman N, Li CK, Shahi M, Poulter NR, Sever PS, Foale RA, Thom SA. Ethnic differences in the hypertensive heart and 24-hour blood pressure profile. Hypertension. 1998 May;31(5):1190-4. doi: 10.1161/01.hyp.31.5.1190.
- Derived from this study: PubMed 30354703Poulter NR, Savopoulos C, Anjum A, Apostolopoulou M, Chapman N, Cross M, Falaschetti E, Fotiadis S, James RM, Kanellos I, Szigeti M, Thom S, Sever P, Thompson D, Hatzitolios AI. Randomized Crossover Trial of the Impact of Morning or Evening Dosing of Antihypertensive Agents on 24-Hour Ambulatory Blood Pressure. Hypertension. 2018 Oct;72(4):870-873. doi: 10.1161/HYPERTENSIONAHA.118.11101.
- Individual participant dataSharing planned: No
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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.
Neil Poulter, MRCS LRCP MBBS MRCP MSc FRCP principal investigator
Imperial College London
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Anti-hypertensive Medication - in people with Hypertension, run by Imperial College London at 2 sites in 2 countries.
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 2 inclusion and 5 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 8 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Greece, United Kingdom. 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?
Yes. Results are posted in the registry (first posted 8 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in 24 Hour Systolic Blood Pressure (time frame: 6 months). 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 NCT01669928, which also lists 8 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 8 Mar 2021.