NCT01379079

Brief Summary

Aspirin is a cornerstone in the secondary prevention of cardiovascular disease (CVD) and is usually taken on awakening, although evidence regarding optimal time of intake is lacking. Recent studies in healthy subjects with mild hypertension showed that aspirin at bedtime decreases blood pressure (-7/5mmHg), whereas intake of aspirin on awakening does not. Additionally, the investigators found that aspirin at bedtime decreases plasma renin activity, catecholamines and cortisol over 24hrs. Time-dependent effects of aspirin have never been studied in patients with CVD, who may use concomitant antihypertensive drugs. Moreover, platelet reactivity has a circadian rhythm, and intake of aspirin at bedtime may attenuate the morning peak in platelet reactivity. The investigators hypothesize that aspirin intake at bedtime compared with on awakening decreases both blood pressure and platelet reactivity over 24h. A randomized open-label blinded endpoint crossover trial in which 250 patients, recruited from primary care, will be included who use aspirin for secondary prevention of CVD and have a stable blood pressure of 149/94mmHg or lower. Study subjects will randomly use both aspirin on awakening and at bedtime during two intervention periods of three months. Blood pressure will be recorded for 24hrs at the end of each treatment period in the patients' normal daily situation. To assess effects on platelet inhibition, thromboxane-B2 levels will be measured in a 24h urine sample at the end of both treatment periods. The investigators will asses differential effects according to time of intake on gastrointestinal complaints and potential minor bleeding events, as well as compliance. The aim of this study is to evaluate the effect of aspirin taken at bedtime compared with on awakening on blood pressure of subjects with stable CVD. In addition, it will generate insights into the effect of aspirin on platelet reactivity over 24hrs, potential side effects and compliance.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
290

participants targeted

Target at P50-P75 for phase_4 hypertension

Timeline
Completed

Started Apr 2011

Typical duration for phase_4 hypertension

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 31, 2011

Completed
1 day until next milestone

Study Start

First participant enrolled

April 1, 2011

Completed
3 months until next milestone

First Posted

Study publicly available on registry

June 23, 2011

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2013

Completed
Last Updated

May 14, 2014

Status Verified

May 1, 2014

Enrollment Period

2.5 years

First QC Date

March 31, 2011

Last Update Submit

May 12, 2014

Conditions

HypertensionCardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

  • change in 24h Ambulant blood pressure measurement

    Primary endpoint: 24-hour Ambulatory blood pressure (ABPM). The primary endpoint will be analysed in primary- and secondary analysis. Primary analysis population: all randomized subjects with complete follow-up ABPM. Includes subjects with invalid ABPM, change in antihypertensive medication during follow-up, and subjects with low compliance. Analyses: 1) paired t-tests: mean 24-hour blood pressure, blood pressure during the day and night. 2)Linear mixed models: timing of aspirin intake, treatment sequence, treatment period, used blood pressure device and interaction terms as fixed effects, and subjects as random effects. Secondary analysis population excludes subjects with invalid ABPM, change of antihypertensive medication, or compliance \<90%. Subgroup analyses: 1) β-blockers: yes/no; 2)Ace-inhibitors: yes/no; 3)Subjects using: a.No β-blockers or Ace-inhibitors; b.β-blockers; c. Ace-inhibitors; d. β-blockers+Ace-inhibitors; 4)Office blood pressure \<140/90 mmHg vs. \>140/90 mmHg.

    after 3 and 6 months

Secondary Outcomes (5)

  • Platelet inhibition

    after 3 and 6 months

  • platelet function and coagulation factors

    baseline and after 3 and 6 months

  • side effects

    baseline and after 3 and 6 months

  • genes involved in blood pressure regulation

    baseline

  • Patient preference

    baseline and after 6 months

Study Arms (2)

aspirin at bedtime

EXPERIMENTAL
Drug: Acetylsalicylic acid

aspirin on awakening

ACTIVE COMPARATOR
Drug: Acetylsalicylic acid lysinate

Interventions

Acetylsalicylic acidDRUG

aspirin intake at bedtime

Also known as: Ascal, Ascal Cardio/Neuro, Carbasalate Calcium
aspirin at bedtime
Acetylsalicylic acid lysinateDRUG

aspirin intake on awakening

Also known as: Ascal, Ascal Cardio/Neuro, Carbasalate Calcium
aspirin on awakening

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Use of low-dose aspirin (acetylsalicylic acid or carbasalate calcium 80- 100mg \[brand names: acetylsalicylic acid cardio, aspirin protect, ascal cardio, carbasalate calcium cardio\]) for secondary prevention of cardiovascular events
  • Stable blood pressure (with or without therapy) between 120/70 and 159/99
  • Age 18-80 year
  • Capacity to give informed consent (IC)

You may not qualify if:

  • Blood pressure lower than 120/70 or higher than 159/99
  • Change in blood pressure lowering medication within the last three months
  • Regular use of non-steroidal anti-inflammatory drugs (NSAID's)
  • Shift workers
  • Evidence of secondary arterial hypertension
  • Pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Leiden University Medical Center

Leiden, 2300 RC, Netherlands

Location

Related Publications (2)

  • Snoep JD, Hovens MM, Pasha SM, Frolich M, Pijl H, Tamsma JT, Huisman MV. Time-dependent effects of low-dose aspirin on plasma renin activity, aldosterone, cortisol, and catecholamines. Hypertension. 2009 Nov;54(5):1136-42. doi: 10.1161/HYPERTENSIONAHA.109.134825. Epub 2009 Oct 5.

    PMID: 19805643BACKGROUND

  • Hermida RC, Ayala DE, Calvo C, Lopez JE. Aspirin administered at bedtime, but not on awakening, has an effect on ambulatory blood pressure in hypertensive patients. J Am Coll Cardiol. 2005 Sep 20;46(6):975-83. doi: 10.1016/j.jacc.2004.08.071.

    PMID: 16168278BACKGROUND

MeSH Terms

Conditions

HypertensionCardiovascular Diseases

Interventions

Aspirincarbaspirin calciumacetylsalicylic acid lysinate

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

SalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • J.G. vd Bom, MD, PhD

    Leiden University Medical Center

    STUDY DIRECTOR

  • T.N. Bonten, MD

    Leiden University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

March 31, 2011

First Posted

June 23, 2011

Study Start

April 1, 2011

Primary Completion

October 1, 2013

Study Completion

October 1, 2013

Last Updated

May 14, 2014

Record last verified: 2014-05

Locations

NL(1)