High-Normal Blood PressurePhase 4NCT00449618
Comparison of Awakening Versus Bedtime Dosing of Aspirin in Pre-Hypertension or Mild Essential Hypertension
A Phase 4 study testing Aspirin 100 mg, Ambulatory blood pressure monitoring and Chronotherapy, timing of medication in people with High-Normal Blood Pressure and Mild Essential Hypertension, run by University of Vigo at 5 sites in Spain.
Trial summary
Aspirin (ASA) has been shown to provide marked benefits in the prevention of cardiovascular events, although the potential direct effects of ASA on cardiovascular function remain uncertain. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- High-Normal Blood Pressure, Mild Essential Hypertension
- What is being tested?
- Aspirin 100 mg, Ambulatory blood pressure monitoring and Chronotherapy, timing of medication
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 5 sitesSpain
- Study dates
- Jan 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- High-normal blood pressure
- Mild essential hypertension
Who cannot join
- Moderate-severe hypertension.
- Secondary hypertension.
- Grade III/IV hypertensive retinopathy.
- Type 1 diabetes.
- Body mass index ≥ 35 kg/m2
- Cerebrovascular or cardiovascular event during the last 12 months prior to inclusion.
Show all 12Show fewer
- Pregnant or lactating females.
- History of malignancy within the past five years.
- Shift workers.
- Obstructive sleep apnea.
- Use of disallowed concomitant medication.
- Intolerant to ambulatory BP monitoring (ABPM).
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Spain5 sites
Centro de Salud de A Guarda
La Guardia, Pontevedra
C.S. Lérez
Pontevedra
Hospital Clínico Universitario de Santiago
Santiago de Compostela, 15701
Centro de Salud de Sardoma
Vigo, Pontevedra, 36214
Centro de Salud de A Doblada
Vigo, Pontevedra
About this study
Official title: A Prospective, Randomized, Multi-Center, Double-Blind Crossover Study to Compare Awakening Versus Bedtime Administration of 100 mg Aspirin or Placebo in Subjects With High-Normal Blood Pressure or Mild Essential Hypertension
Aspirin (ASA) has been shown to provide marked benefits in the prevention of cardiovascular events, although the potential direct effects of ASA on cardiovascular function remain uncertain. Previous studies have demonstrated that ASA is a potent antioxidative agent that markedly reduces vascular production of superoxide in normotensive and hypertensive rats. In addition, ASA was found to prevent angiotensin II-induced hypertension and cardiovascular hypertrophy, mainly through its antioxidative properties in preventing the generation of superoxide, although ASA apparently did not appear to reduce hypertensive levels of blood pressure (BP). Moreover, recent results have demonstrated that ASA induces nitric oxide (NO) release from vascular endothelium. No attention has been paid, so far, to potential administration time-dependent effects in these studies.
Previous laboratory animal and clinical trial research convincingly demonstrates administration time-dependent (with reference to circadian rhythms) effects of ASA. Thus, the effects of ASA upon lipoperoxides, β-adrenergic receptors, and BP in clinically healthy subjects depend on the circadian timing of ASA administration. Most important, the administration time-dependent influence of ASA on BP was previously demonstrated in a randomized trial on healthy women and in other independent, double-blind, randomized, placebo-controlled clinical trials. The first was conducted on clinically healthy subjects, a second one on normotensive and hypertensive subjects, a third one on pregnant women at high risk for preeclampsia and a fourth one in previously untreated patients with mild hypertension. The findings of these BP studies are consistent; the BP-lowering effect of low-dose ASA is achieved when administered at bedtime but not upon awakening.
In keeping with the chronopharmacological effects of ASA and the previous findings suggesting that ASA at low dose may have a potential beneficial effect on BP, this prospective, randomized, double-blind, crossover study will investigate the potential influence of ASA on BP in subjects with either high-normal BP or diagnosis of mild (grade 1) hypertension. The subjects will receive low-dose ASA or placebo at different times of the day according to their rest-activity cycle, and will be evaluated by 48-hour ambulatory BP monitoring before and after 6 weeks of pharmacologic intervention.
Read the detailed description
This is a multi-center, prospective, randomized, four-arm, crossover study with double-blind design.
At Visit 1 (week -1) patients will be assessed for eligibility for study participation. Subjects will be advised that study entry cannot be fully determined until the completion of the screening period when all exclusion/inclusion criteria are entirely assessed. Subjects will perform Visit 2 as soon as their laboratory results of Visit 1 are available. At baseline (Visit 2/Day 1), a total of 300 subjects whose eligibility is confirmed will be randomized in a 1:1:1 ratio to one of the treatment groups (aspirin upon awakening, aspirin at bedtime, or placebo--half on awakening, half at bedtime). Subjects will start a first double-blind treatment phase with a total duration of 6 weeks. During this period the subjects will be receiving either aspirin 100 mg or placebo at two different circadian times (either after awakening from nighttime sleep or before bedtime) until the end of this study phase (Visit 3). After this first treatment phase, all subjects will undergo a 2-week wash-out phase with placebo. At Visit 4 (week 8), all subjects will be crossed-over in terms of the circadian time, but keeping their original treatment (either aspirin or placebo), and followed up for a second treatment phase of 6 weeks.
The study duration including all the phases will be 15 weeks.
Safety and efficacy will be assessed at the end of every treatment phase, i.e., at Visits 3 and 5. Safety will also be assessed by phone calls 2 weeks after the initiation of each active treatment phase (weeks 2 and 10). Subjects may be requested to attend the clinic for further evaluation on those weeks if they present any adverse effect.
- Being tested
- Aspirin 100 mg, Ambulatory blood pressure monitoring, Chronotherapy, timing of medication, Placebo
- Keywords
- Aspirin, Ambulatory blood pressure monitoring, Chronotherapy, Circadian
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspirin 100 mgDrug
dose of 100 mg administered on awakening or at 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
Chronotherapy, timing of medicationProcedure or surgery
Dosing on awakening versus bedtime
PlaceboDrug
Use of placebo on awakening versus bedtime
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Aspirin 100 mg on awakening Receives: Drug: Aspirin 100 mg; Device: Ambulatory blood pressure monitoring; Procedure: Chronotherapy, timing of medication |
| 2 | Active comparator | Aspirin 100 mg at bedtime Receives: Drug: Aspirin 100 mg; Device: Ambulatory blood pressure monitoring; Procedure: Chronotherapy, timing of medication |
| 3 | Placebo comparator | Placebo on awakening Receives: Device: Ambulatory blood pressure monitoring; Procedure: Chronotherapy, timing of medication; Drug: Placebo |
| 4 | Placebo comparator | Placebo at bedtime Receives: Device: Ambulatory blood pressure monitoring; Procedure: Chronotherapy, timing of medication; Drug: Placebo |
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 aspirin by testing the hypothesis of superior 24 hour systolic BP (SBP) lowering compared with either aspirin administered on awakening or with placebo at any circadian time
Measured: 14 weeks
Secondary outcomes (4)
To demonstrate that aspirin at bedtime is more effective than aspirin upon awakening and placebo in terms of 24 hour diastolic BP (DBP) lowering
Measured: 14 weeks
To demonstrate that aspirin at bedtime is more effective in non-dipper subjects as compared to dippers in terms of nocturnal SBP/DBP lowering, and that this effect is superior to any potential effect on BP of aspirin upon awakening or placebo
Measured: 14 weeks
To demonstrate that aspirin at bedtime offers a similar safety profile to aspirin upon awakening and to placebo
Measured: 14 weeks
To demonstrate that compliance with aspirin at bedtime is similar to compliance with either aspirin upon awakening or placebo
Measured: 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2007 (estimated)
- Study startJan 2007
- Primary completionDec 2008
- Study completionDec 2008
Why it stopped: Not enough recruitment during the proposed period.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High-Normal Blood PressureStudies 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
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vigo
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Clinico Universitario de Santiago, Bayer
- Investigators
- Ramon C Hermida, Ph.D., Principal investigator, University of Vigo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00449618
- Sponsor's protocol ID
- ASA100-2004/2
- Other IDs
- 2004-004987-65, 2006-004652-21, 2004
- Status last verified
- Dec 2008
- First submitted
- 19 Mar 2007
- Last updated
- 5 Jan 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Multi-Center, Double-Blind Crossover Study to Compare Awakening Versus Bedtime Administration of 100 mg Aspirin or Placebo in Subjects With High-Normal Blood Pressure or Mild Essential Hypertension
- ClinicalTrials.gov ID
- NCT00449618
- Acronym / sponsor ID
- ASA100-2004/2
- Keywords
- Aspirin, Ambulatory blood pressure monitoring, Chronotherapy, Circadian
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not enough recruitment during the proposed period.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of VigoUniversity, hospital or other
- Collaborators
- Hospital Clinico Universitario de Santiago, Bayer
- Study start
- Jan 2007
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 20 Mar 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.
Aspirin (ASA) has been shown to provide marked benefits in the prevention of cardiovascular events, although the potential direct effects of ASA on cardiovascular function remain uncertain. Previous studies have demonstrated that ASA is a potent antioxidative agent that markedly reduces vascular production of superoxide in normotensive and hypertensive rats. In addition, ASA was found to prevent angiotensin II-induced hypertension and cardiovascular hypertrophy, mainly through its antioxidative properties in preventing the generation of superoxide, although ASA apparently did not appear to reduce hypertensive levels of blood pressure (BP). Moreover, recent results have demonstrated that ASA induces nitric oxide (NO) release from vascular endothelium. No attention has been paid, so far, to potential administration time-dependent effects in these studies.
Previous laboratory animal and clinical trial research convincingly demonstrates administration time-dependent (with reference to circadian rhythms) effects of ASA. Thus, the effects of ASA upon lipoperoxides, β-adrenergic receptors, and BP in clinically healthy subjects depend on the circadian timing of ASA administration. Most important, the administration time-dependent influence of ASA on BP was previously demonstrated in a randomized trial on healthy women and in other independent, double-blind, randomized, placebo-controlled clinical trials. The first was conducted on clinically healthy subjects, a second one on normotensive and hypertensive subjects, a third one on pregnant women at high risk for preeclampsia and a fourth one in previously untreated patients with mild hypertension. The findings of these BP studies are consistent; the BP-lowering effect of low-dose ASA is achieved when administered at bedtime but not upon awakening.
In keeping with the chronopharmacological effects of ASA and the previous findings suggesting that ASA at low dose may have a potential beneficial effect on BP, this prospective, randomized, double-blind, crossover study will investigate the potential influence of ASA on BP in subjects with either high-normal BP or diagnosis of mild (grade 1) hypertension. The subjects will receive low-dose ASA or placebo at different times of the day according to their rest-activity cycle, and will be evaluated by 48-hour ambulatory BP monitoring before and after 6 weeks of pharmacologic intervention.
Detailed description
This is a multi-center, prospective, randomized, four-arm, crossover study with double-blind design.
At Visit 1 (week -1) patients will be assessed for eligibility for study participation. Subjects will be advised that study entry cannot be fully determined until the completion of the screening period when all exclusion/inclusion criteria are entirely assessed. Subjects will perform Visit 2 as soon as their laboratory results of Visit 1 are available. At baseline (Visit 2/Day 1), a total of 300 subjects whose eligibility is confirmed will be randomized in a 1:1:1 ratio to one of the treatment groups (aspirin upon awakening, aspirin at bedtime, or placebo--half on awakening, half at bedtime). Subjects will start a first double-blind treatment phase with a total duration of 6 weeks. During this period the subjects will be receiving either aspirin 100 mg or placebo at two different circadian times (either after awakening from nighttime sleep or before bedtime) until the end of this study phase (Visit 3). After this first treatment phase, all subjects will undergo a 2-week wash-out phase with placebo. At Visit 4 (week 8), all subjects will be crossed-over in terms of the circadian time, but keeping their original treatment (either aspirin or placebo), and followed up for a second treatment phase of 6 weeks.
The study duration including all the phases will be 15 weeks.
Safety and efficacy will be assessed at the end of every treatment phase, i.e., at Visits 3 and 5. Safety will also be assessed by phone calls 2 weeks after the initiation of each active treatment phase (weeks 2 and 10). Subjects may be requested to attend the clinic for further evaluation on those weeks if they present any adverse effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Aspirin 100 mg, Device: Ambulatory blood pressure monitoring, Procedure: Chronotherapy, timing of medicationAspirin 100 mg on awakening |
| 2 | Active comparator | Drug: Aspirin 100 mg, Device: Ambulatory blood pressure monitoring, Procedure: Chronotherapy, timing of medicationAspirin 100 mg at bedtime |
| 3 | Placebo comparator | Device: Ambulatory blood pressure monitoring, Procedure: Chronotherapy, timing of medication, Drug: PlaceboPlacebo on awakening |
| 4 | Placebo comparator | Device: Ambulatory blood pressure monitoring, Procedure: Chronotherapy, timing of medication, Drug: PlaceboPlacebo at bedtime |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- High-normal blood pressure
- Mild essential hypertension
Key exclusion criteria (12 listed)
- Moderate-severe hypertension.
- Secondary hypertension.
- Grade III/IV hypertensive retinopathy.
- Type 1 diabetes.
- Body mass index ≥ 35 kg/m2
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 |
|---|---|---|
| Aspirin 100 mgdose of 100 mg administered on awakening or at 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, 3, 4 |
| Chronotherapy, timing of medicationDosing on awakening versus bedtime | Procedure or surgery | 1, 2, 3, 4 |
| PlaceboUse of placebo on awakening versus bedtime | Drug | 3, 4 |
Primary outcome
To demonstrate the efficacy of bedtime administration of aspirin by testing the hypothesis of superior 24 hour systolic BP (SBP) lowering compared with either aspirin administered on awakening or with placebo at any circadian time
Time frame: 14 weeks
4 secondary outcomes
To demonstrate that aspirin at bedtime is more effective than aspirin upon awakening and placebo in terms of 24 hour diastolic BP (DBP) lowering
Time frame: 14 weeks
To demonstrate that aspirin at bedtime is more effective in non-dipper subjects as compared to dippers in terms of nocturnal SBP/DBP lowering, and that this effect is superior to any potential effect on BP of aspirin upon awakening or placebo
Time frame: 14 weeks
To demonstrate that aspirin at bedtime offers a similar safety profile to aspirin upon awakening and to placebo
Time frame: 14 weeks
To demonstrate that compliance with aspirin at bedtime is similar to compliance with either aspirin upon awakening or placebo
Time frame: 14 weeks
Results and safety
The study was stopped early (reason given: Not enough recruitment during the proposed period.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2009.
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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, Ph.D. principal investigator
University of Vigo
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 Aspirin 100 mg, Ambulatory blood pressure monitoring and Chronotherapy, timing of medication in people with High-Normal Blood Pressure and Mild Essential Hypertension, run by University of Vigo at 5 sites 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 2 inclusion and 12 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: stopped early, as of the sponsor's last update on 5 Jan 2009. 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 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: Not enough recruitment during the proposed period.). Results are not available in the source record.
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 aspirin by testing the hypothesis of superior 24 hour systolic BP (SBP) lowering compared with either aspirin administered on awakening or with placebo at any circadian time (time frame: 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jan 2009.