A Phase 4 interventional study of Aspirin 100 mg and Ambulatory blood pressure monitoring in High-Normal Blood Pressure and Mild Essential Hypertension, sponsored by University of Vigo. Terminated at 5 sites in Spain. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2009-01-05.
Sponsored by University of Vigo · Phase 4, Interventional, and Treatment
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.
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.
6,689 studies on the registry are indexed under Hypertension; 965 are open to participants now.
This study's enrollment of 23 is below the median of 90 across 4,995 interventional studies indexed under Hypertension.
Browse Hypertension studies →University of Vigo is the lead sponsor of 53 studies on the registry; 13 are open to participants now.
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Exclusion Criteria:
Aspirin 100 mg on awakening
Drug: Aspirin 100 mg · Device: Ambulatory blood pressure monitoring · Procedure: Chronotherapy, timing of medication
Aspirin 100 mg at bedtime
Drug: Aspirin 100 mg · Device: Ambulatory blood pressure monitoring · Procedure: Chronotherapy, timing of medication
Placebo on awakening
Device: Ambulatory blood pressure monitoring · Procedure: Chronotherapy, timing of medication · Drug: Placebo
Placebo at bedtime
Device: Ambulatory blood pressure monitoring · Procedure: Chronotherapy, timing of medication · Drug: Placebo
dose of 100 mg administered on awakening or at bedtime
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
Dosing on awakening versus bedtime
Use of placebo on awakening versus bedtime
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
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
This study is terminated, as verified in Dec 2008. You cannot join it, but the record below documents what was studied.
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University of Vigo