HypertensionPhase 4HYCCRANCT00473174
Comparison of Awakening Versus Bedtime Dosing of Ramipril in Subjects With Essential Hypertension
A Phase 4 study testing Ramipril and ambulatory blood pressure monitoring in people with Hypertension, run by University of Vigo at 1 site in Spain.
Trial summary
This prospective chronotherapy trial will investigate the potential differing efficacy of ramipril in doses from 5 to 10 mg/day when administered, as a monotherapy either upon awakening from nighttime sleep or at bedtime, to diurnally active patients with grade 1 or 2 essential hypertension, who will be evaluated by… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- Ramipril and ambulatory blood pressure monitoring
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteSpain
- Study dates
- Mar 2007to Dec 2008
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Essential hypertension
Who cannot join
- Severe hypertension.
- Secondary hypertension.
- Grade III/IV hypertensive retinopathy.
- Type 1 diabetes.
- Cerebrovascular or cardiovascular event during the last 12 months prior to inclusion.
- Pregnant or lactating females.
Show all 11Show fewer
- History of malignancy within the past five years.
- Shift workers.
- Obstructive sleep apnea.
- Use of disallowed concomitant medication.
- Intolerant to ABPM.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Clínico Universitario de Santiago
Santiago de Compostela, 15701
About this study
Official title: A Prospective, Randomized, Open Label, Blinded-endpoint Study to Compare Awakening Versus Bedtime Administration of 5-10 mg Ramipril in Terms of Systolic Blood Pressure Lowering Determined by ABPM in Subjects With Mild-to-moderate Essential
This prospective chronotherapy trial will investigate the potential differing efficacy of ramipril in doses from 5 to 10 mg/day when administered, as a monotherapy either upon awakening from nighttime sleep or at bedtime, to diurnally active patients with grade 1 or 2 essential hypertension, who will be evaluated by 48-hour ABPM before and after pharmacologic intervention. The benefits from this trial may be extremely important, taking into account
- the high prevalence of non-dipping among patients with essential hypertension
- the need for a proper 24-hour BP control with particular emphasis on the regulation of nighttime resting BP mean
- the lacking information on the administration-time dependent effects on BP of ramipril, a widely used ACEI in doses of 5-10 mg/day.
Read the detailed description
Several attributes of the cardiovascular system, including blood pressure (BP) and heart rate (HR), are characterized by predictable changes during the 24 hours for the most part in synchrony with the rest-activity cycle. During the past two decades specific features of the 24-hour BP pattern have been assessed as potential sources of injury to target tissues and as triggers of cardiac and cerebrovascular events in hypertensive patients. A growing number of studies indicate the reduction of the normal 10 to 20% sleep-time BP decline (non-dipper pattern) is associated with elevated risk of end-organ injury, particularly to the heart (left ventricular hypertrophy and myocardial infarct), brain (stoke) and kidney (albuminuria and progression to end-stage renal failure). Accordingly, there is growing interest in how to tailor the treatment of hypertensive patients according to their circadian BP pattern.
Clinical studies demonstrated a different effect of the ACEIs benazepril, enalapril, perindopril, quinapril, spirapril, and trandolapril when dosed in the morning versus the evening. A small trial on 33 patients with essential hypertension showed that a low dose of 2.5 mg/day ramipril more effectively reduced daytime BP when it was administered in the morning and more effectively reduced nighttime BP when it was administered in the evening. In the HOPE (Heart Outcomes Prevention Evaluation) study patients in the active treatment group received ramipril at bedtime. Results from a small substudy, in which hypertensive patients were evaluated with 24-hour ambulatory BP monitoring (ABPM), showed a marked BP reduction particularly during nighttime sleep, thereby reducing the prevalence of non-dippers. The authors concluded that the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may relate to its improved effect (i.e., increase in the diurnal/nocturnal BP ratio) on the non-dipping BP patterns.
In keeping with the documented administration-time dependent effects on BP regulation of other ACEI, this prospective chronotherapy trial will investigate the potential differing efficacy of ramipril in doses from 5 to 10 mg/day when administered, as a monotherapy either upon awakening from nighttime sleep or at bedtime, to diurnally active patients with grade 1 or 2 essential hypertension, who will be evaluated by 48-hour ABPM before and after pharmacologic intervention. The benefits from this trial may be extremely important, taking into account 1) the high prevalence of non-dipping among patients with essential hypertension, 2) the need for a proper 24-hour BP control with particular emphasis on the regulation of nighttime resting BP mean, and 3) the lacking information on the administration-time dependent effects on BP of ramipril, a widely used ACEI in doses of 5-10 mg/day.
- Conditions
- Hypertension
- Being tested
- Ramipril, ambulatory blood pressure monitoring
- Keywords
- Ramipril, Ambulatory blood pressure monitoring, Chronotherapy, Circadian, Non-dipper
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RamiprilDrug
Dosing on awakening versus bedtime
ambulatory blood pressure monitoringDevice
Blood pressure measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Ramipril on awakening Receives: Drug: Ramipril; Device: ambulatory blood pressure monitoring |
| 2 | Active comparator | Ramipril at bedtime Receives: Drug: Ramipril; Device: ambulatory blood pressure monitoring |
What is being measured
The primary outcome is the main question the study is designed to answer.
To demonstrate the efficacy of bedtime administration of ramipril in subjects with essential hypertension by testing the hypothesis of superior nocturnal SBP lowering in ABPM measurements compared with ramipril administered on awakening
Measured: Three months
Secondary outcomes (5)
To demonstrate that ramipril at bedtime is more effective than ramipril upon awakening in terms of nocturnal DBP lowering in ABPM
Measured: Three months
To demonstrate that ramipril at bedtime is not inferior to ramipril upon awakening in terms of 24-hour SBP/DBP lowering in ABPM
Measured: Three months
To demonstrate that ramipril at bedtime is more effective than ramipril upon awakening in terms of increasing the diurnal/nocturnal SBP and DBP ratio determined by ABPM
Measured: Three months
To demonstrate that ramipril at bedtime offers a similar safety profile than ramipril upon awakening
Measured: Three months
To demonstrate that compliance with ramipril at bedtime is similar to compliance of ramipril upon awakening
Measured: Three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2007 (estimated)
- Study startMar 2007
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- 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
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vigo
- Sponsor type
- University, hospital or other
- Collaborators
- King Pharmaceuticals is now a wholly owned subsidiary of Pfizer
- Investigators
- Ramon C Hermida, PhD, Principal investigator, University of Vigo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00473174
- Sponsor's protocol ID
- HYCCRA-2006/01
- Other IDs
- Eudract-2006-006107-37
- Acronym
- HYCCRA
- Status last verified
- Sep 2009
- First submitted
- 11 May 2007
- Last updated
- 2 Sep 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hermida RC, Ayala DE. Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: improved blood pressure control with bedtime dosing. Hypertension. 2009 Jul;54(1):40-6. doi: 10.1161/HYPERTENSIONAHA.109.130203. Epub 2009 May 11.
PubMed 19433778
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Open Label, Blinded-endpoint Study to Compare Awakening Versus Bedtime Administration of 5-10 mg Ramipril in Terms of Systolic Blood Pressure Lowering Determined by ABPM in Subjects With Mild-to-moderate Essential
- ClinicalTrials.gov ID
- NCT00473174
- Acronym / sponsor ID
- HYCCRA / HYCCRA-2006/01
- Conditions
- Hypertension
- Keywords
- Ramipril, Ambulatory blood pressure monitoring, Chronotherapy, Circadian, Non-dipper
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University of VigoUniversity, hospital or other
- Collaborators
- King Pharmaceuticals is now a wholly owned subsidiary of Pfizer
- Study start
- Mar 2007
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 14 May 2007 (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.
This prospective chronotherapy trial will investigate the potential differing efficacy of ramipril in doses from 5 to 10 mg/day when administered, as a monotherapy either upon awakening from nighttime sleep or at bedtime, to diurnally active patients with grade 1 or 2 essential hypertension, who will be evaluated by 48-hour ABPM before and after pharmacologic intervention. The benefits from this trial may be extremely important, taking into account
- the high prevalence of non-dipping among patients with essential hypertension
- the need for a proper 24-hour BP control with particular emphasis on the regulation of nighttime resting BP mean
- the lacking information on the administration-time dependent effects on BP of ramipril, a widely used ACEI in doses of 5-10 mg/day.
Detailed description
Several attributes of the cardiovascular system, including blood pressure (BP) and heart rate (HR), are characterized by predictable changes during the 24 hours for the most part in synchrony with the rest-activity cycle. During the past two decades specific features of the 24-hour BP pattern have been assessed as potential sources of injury to target tissues and as triggers of cardiac and cerebrovascular events in hypertensive patients. A growing number of studies indicate the reduction of the normal 10 to 20% sleep-time BP decline (non-dipper pattern) is associated with elevated risk of end-organ injury, particularly to the heart (left ventricular hypertrophy and myocardial infarct), brain (stoke) and kidney (albuminuria and progression to end-stage renal failure). Accordingly, there is growing interest in how to tailor the treatment of hypertensive patients according to their circadian BP pattern.
Clinical studies demonstrated a different effect of the ACEIs benazepril, enalapril, perindopril, quinapril, spirapril, and trandolapril when dosed in the morning versus the evening. A small trial on 33 patients with essential hypertension showed that a low dose of 2.5 mg/day ramipril more effectively reduced daytime BP when it was administered in the morning and more effectively reduced nighttime BP when it was administered in the evening. In the HOPE (Heart Outcomes Prevention Evaluation) study patients in the active treatment group received ramipril at bedtime. Results from a small substudy, in which hypertensive patients were evaluated with 24-hour ambulatory BP monitoring (ABPM), showed a marked BP reduction particularly during nighttime sleep, thereby reducing the prevalence of non-dippers. The authors concluded that the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may relate to its improved effect (i.e., increase in the diurnal/nocturnal BP ratio) on the non-dipping BP patterns.
In keeping with the documented administration-time dependent effects on BP regulation of other ACEI, this prospective chronotherapy trial will investigate the potential differing efficacy of ramipril in doses from 5 to 10 mg/day when administered, as a monotherapy either upon awakening from nighttime sleep or at bedtime, to diurnally active patients with grade 1 or 2 essential hypertension, who will be evaluated by 48-hour ABPM before and after pharmacologic intervention. The benefits from this trial may be extremely important, taking into account 1) the high prevalence of non-dipping among patients with essential hypertension, 2) the need for a proper 24-hour BP control with particular emphasis on the regulation of nighttime resting BP mean, and 3) the lacking information on the administration-time dependent effects on BP of ramipril, a widely used ACEI in doses of 5-10 mg/day.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Ramipril, Device: ambulatory blood pressure monitoringRamipril on awakening |
| 2 | Active comparator | Drug: Ramipril, Device: ambulatory blood pressure monitoringRamipril at bedtime |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Essential hypertension
Key exclusion criteria (11 listed)
- Severe hypertension.
- Secondary hypertension.
- Grade III/IV hypertensive retinopathy.
- Type 1 diabetes.
- Cerebrovascular or cardiovascular event during the last 12 months prior to inclusion.
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 |
|---|---|---|
| RamiprilDosing on awakening versus bedtime | Drug | 1, 2 |
| ambulatory blood pressure monitoringBlood pressure measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours | Device | 1, 2 |
Primary outcome
To demonstrate the efficacy of bedtime administration of ramipril in subjects with essential hypertension by testing the hypothesis of superior nocturnal SBP lowering in ABPM measurements compared with ramipril administered on awakening
Time frame: Three months
5 secondary outcomes
To demonstrate that ramipril at bedtime is more effective than ramipril upon awakening in terms of nocturnal DBP lowering in ABPM
Time frame: Three months
To demonstrate that ramipril at bedtime is not inferior to ramipril upon awakening in terms of 24-hour SBP/DBP lowering in ABPM
Time frame: Three months
To demonstrate that ramipril at bedtime is more effective than ramipril upon awakening in terms of increasing the diurnal/nocturnal SBP and DBP ratio determined by ABPM
Time frame: Three months
To demonstrate that ramipril at bedtime offers a similar safety profile than ramipril upon awakening
Time frame: Three months
To demonstrate that compliance with ramipril at bedtime is similar to compliance of ramipril upon awakening
Time frame: Three 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 2 Sep 2009.
- Results publication: PubMed 19433778Hermida RC, Ayala DE. Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: improved blood pressure control with bedtime dosing. Hypertension. 2009 Jul;54(1):40-6. doi: 10.1161/HYPERTENSIONAHA.109.130203. Epub 2009 May 11.
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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.
Ramon C Hermida, PhD principal investigator
University of Vigo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ramipril and ambulatory blood pressure monitoring in people with Hypertension, run by University of Vigo at 1 site in Spain.
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 1 inclusion and 11 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 2 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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?
To demonstrate the efficacy of bedtime administration of ramipril in subjects with essential hypertension by testing the hypothesis of superior nocturnal SBP lowering in ABPM measurements compared with ramipril administered on awakening (time frame: Three 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 NCT00473174, which also lists 1 linked publication.
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 2 Sep 2009.