Ignite Creation Date:
2024-05-05 @ 5:24 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00449618
Status:
TERMINATED
Last Update Posted:
2009-01-05
First Post:
2007-03-19
Brief Title:
Comparison of Awakening Versus Bedtime Dosing of Aspirin in Pre-Hypertension or Mild Essential Hypertension
Sponsor:
University of Vigo
Organization:
University of Vigo
Study Overview
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
Status:
TERMINATED
Status Verified Date:
2008-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not enough recruitment during the proposed period
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 exclusioninclusion criteria are entirely assessed Subjects will perform Visit 2 as soon as their laboratory results of Visit 1 are available At baseline Visit 2Day 1 a total of 300 subjects whose eligibility is confirmed will be randomized in a 111 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 ie 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
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 exclusioninclusion criteria are entirely assessed Subjects will perform Visit 2 as soon as their laboratory results of Visit 1 are available At baseline Visit 2Day 1 a total of 300 subjects whose eligibility is confirmed will be randomized in a 111 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 ie 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2006-004652-21 | None | None | None |
| 2004-004987-65 | None | None | None |