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Comparison of Awakening Versus Bedtime Dosing of Aspirin in Pre-Hypertension or Mild Essential Hypertension

Primary Purpose

High-Normal Blood Pressure, Mild Essential Hypertension

Status
Terminated
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Aspirin 100 mg
Ambulatory blood pressure monitoring
Chronotherapy, timing of medication
Placebo
Sponsored by
University of Vigo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High-Normal Blood Pressure focused on measuring Aspirin, Ambulatory blood pressure monitoring, Chronotherapy, Circadian

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • High-normal blood pressure
  • Mild essential hypertension

Exclusion Criteria:

  • 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.
  • 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).

Sites / Locations

  • Centro de Salud de A Guarda
  • Centro de Salud de Sardoma
  • Centro de Salud de A Doblada
  • C.S. Lérez
  • Hospital Clínico Universitario de Santiago

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Placebo Comparator

Arm Label

1

2

3

4

Arm Description

Aspirin 100 mg on awakening

Aspirin 100 mg at bedtime

Placebo on awakening

Placebo at bedtime

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

To demonstrate that aspirin at bedtime is more effective than aspirin upon awakening and placebo in terms of 24 hour diastolic BP (DBP) lowering
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
To demonstrate that aspirin at bedtime offers a similar safety profile to aspirin upon awakening and to placebo
To demonstrate that compliance with aspirin at bedtime is similar to compliance with either aspirin upon awakening or placebo

Full Information

First Posted
March 19, 2007
Last Updated
December 31, 2008
Sponsor
University of Vigo
Collaborators
Hospital Clinico Universitario de Santiago, Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00449618
Brief Title
Comparison of Awakening Versus Bedtime Dosing of Aspirin in Pre-Hypertension or Mild Essential Hypertension
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2008
Overall Recruitment Status
Terminated
Why Stopped
Not enough recruitment during the proposed period.
Study Start Date
January 2007 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Vigo
Collaborators
Hospital Clinico Universitario de Santiago, Bayer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High-Normal Blood Pressure, Mild Essential Hypertension
Keywords
Aspirin, Ambulatory blood pressure monitoring, Chronotherapy, Circadian

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Aspirin 100 mg on awakening
Arm Title
2
Arm Type
Active Comparator
Arm Description
Aspirin 100 mg at bedtime
Arm Title
3
Arm Type
Placebo Comparator
Arm Description
Placebo on awakening
Arm Title
4
Arm Type
Placebo Comparator
Arm Description
Placebo at bedtime
Intervention Type
Drug
Intervention Name(s)
Aspirin 100 mg
Intervention Description
dose of 100 mg administered on awakening or at bedtime
Intervention Type
Device
Intervention Name(s)
Ambulatory blood pressure monitoring
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Chronotherapy, timing of medication
Intervention Description
Dosing on awakening versus bedtime
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Use of placebo on awakening versus bedtime
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
To demonstrate that aspirin at bedtime offers a similar safety profile to aspirin upon awakening and to placebo
Time Frame
14 weeks
Title
To demonstrate that compliance with aspirin at bedtime is similar to compliance with either aspirin upon awakening or placebo
Time Frame
14 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: High-normal blood pressure Mild essential hypertension Exclusion Criteria: 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. 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ramon C Hermida, Ph.D.
Organizational Affiliation
University of Vigo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centro de Salud de A Guarda
City
La Guardia
State/Province
Pontevedra
Country
Spain
Facility Name
Centro de Salud de Sardoma
City
Vigo
State/Province
Pontevedra
ZIP/Postal Code
36214
Country
Spain
Facility Name
Centro de Salud de A Doblada
City
Vigo
State/Province
Pontevedra
Country
Spain
Facility Name
C.S. Lérez
City
Pontevedra
Country
Spain
Facility Name
Hospital Clínico Universitario de Santiago
City
Santiago de Compostela
ZIP/Postal Code
15701
Country
Spain

12. IPD Sharing Statement

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Comparison of Awakening Versus Bedtime Dosing of Aspirin in Pre-Hypertension or Mild Essential Hypertension

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