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

NCT00449618 | Terminated Phase 4 DMC

• 3 other identifiers: ASA100-2004/22004-004987-652006-004652-21
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 5

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.

Conditions

High-Normal Blood Pressure; Mild Essential Hypertension

Keywords

Aspirin; Ambulatory blood pressure monitoring; Chronotherapy; Circadian

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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

  14 weeks

• To demonstrate that aspirin at bedtime offers a similar safety profile to aspirin upon awakening and to placebo

  14 weeks

• To demonstrate that compliance with aspirin at bedtime is similar to compliance with either aspirin upon awakening or placebo

  14 weeks

Study Arms (4)

1

ACTIVE COMPARATOR

Aspirin 100 mg on awakening

Drug: Aspirin 100 mg; Device: Ambulatory blood pressure monitoring; Procedure: Chronotherapy, timing of medication

2

ACTIVE COMPARATOR

Aspirin 100 mg at bedtime

Drug: Aspirin 100 mg; Device: Ambulatory blood pressure monitoring; Procedure: Chronotherapy, timing of medication

3

PLACEBO COMPARATOR

Placebo on awakening

Device: Ambulatory blood pressure monitoring; Procedure: Chronotherapy, timing of medication; Drug: Placebo

4

PLACEBO COMPARATOR

Placebo at bedtime

Device: Ambulatory blood pressure monitoring; Procedure: Chronotherapy, timing of medication; Drug: Placebo

Interventions

Aspirin 100 mg DRUG

dose of 100 mg administered on awakening or at bedtime

1; 2

Ambulatory blood pressure monitoring DEVICE

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

1; 2; 3; 4

Chronotherapy, timing of medication PROCEDURE

Dosing on awakening versus bedtime

1; 2; 3; 4

Placebo DRUG

Use of placebo on awakening versus bedtime

3; 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• High-normal blood pressure
• Mild essential hypertension

You may not qualify if:

• Moderate-severe hypertension.
• Secondary hypertension.
• Grade III/IV hypertensive retinopathy.
• Type 1 diabetes.
• Body mass index ≥ 35 kg/m2
• 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).

Sponsors & Collaborators

• University of Vigo: lead
• Hospital Clinico Universitario de Santiago: collaborator
• Bayer: collaborator

Study Sites (5)

Centro de Salud de A Guarda

La Guardia, Pontevedra, Spain

Location

Centro de Salud de Sardoma

Vigo, Pontevedra, 36214, Spain

Location

Centro de Salud de A Doblada

Vigo, Pontevedra, Spain

Location

C.S. Lérez

Pontevedra, Spain

Location

Hospital Clínico Universitario de Santiago

Santiago de Compostela, 15701, Spain

Location

MeSH Terms

Interventions

Aspirin; Blood Pressure Monitoring, Ambulatory; Chronotherapy

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Blood Pressure Determination; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Monitoring, Ambulatory; Monitoring, Physiologic; Therapeutics

Study Officials

• Ramon C Hermida, Ph.D.

  University of Vigo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 19, 2007
• First Posted: March 20, 2007
• Study Start: January 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: January 5, 2009

Record last verified: 2008-12

Locations

ES (5)