NCT01900639

Brief Summary

Low-dose 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. Platelet reactivity follows a circadian rhythm, with a peak in the morning, contributing to the morning peak of cardiovascular disease. Due to its short half life, aspirin only inhibits platelets which are present at the time of intake. Thus, the timing of aspirin intake may influence its inhibitory effect on platelets and intake of aspirin at bedtime may attenuate the morning peak of platelet reactivity. The time-dependent effect of aspirin on circadian rhythm of platelet function has never been studied before. We hypothesize that aspirin intake at bedtime compared with intake on awakening results in a reduction of the morning peak in platelet reactivity.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
14

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Jul 2013

Shorter than P25 for phase_4

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

Study Start

First participant enrolled

July 1, 2013

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

July 12, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 16, 2013

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2014

Completed
Last Updated

February 20, 2014

Status Verified

February 1, 2014

Enrollment Period

6 months

First QC Date

July 12, 2013

Last Update Submit

February 19, 2014

Conditions

AspirinCircadian RhythmPlatelet ActivationCardiovascular Diseases

Keywords

aspirincircadian rhythmplatelet reactivityplatelet activationtime dependent

Outcome Measures

Primary Outcomes (1)

  • Circadian rhythm of platelet reactivity

    Platelet reactivity will be measured by VerifyNow-aspirin assay, serum thromboxane B2, and flow-cytometry.

    24hour rhythm of platelet reactivity

Study Arms (2)

aspirin on awakening

ACTIVE COMPARATOR

intake of 80 acetylsalicylic acid on awakening for 2 weeks

Behavioral: change time of intake of aspirin

aspirin at bedtime

EXPERIMENTAL

intake of 80mg acetylsalicylic acis at bedtime

Behavioral: change time of intake of aspirin

Interventions

change time of intake of aspirinBEHAVIORAL
aspirin at bedtimeaspirin on awakening

Eligibility Criteria

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

You may qualify if:

  • Healthy subject
  • Age \>18yrs
  • Capacity to give informed consent (IC)

You may not qualify if:

  • Active chronic disease
  • Use of any other medication
  • History of: major bleeding events, known bleeding diathesis or disorder, cardiovascular disease, malignancy
  • Known allergy to salicylates
  • Platelet count \< 150 \* 109/L
  • VerifyNow Aspirin Reaction Units \<550 Aspirin Reaction Units (ARU)
  • Smoking
  • Shift work in preceding 2 months
  • Extreme chronotypes, defined as regular (\>2 days/week) bedtime \<22:00h or \>24:00h and/or awakening \<6:00h or \>9:00h
  • Pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Leiden University Medical Center

Leiden, 2300RC, Netherlands

Location

Related Publications (5)

  • Tofler GH, Brezinski D, Schafer AI, Czeisler CA, Rutherford JD, Willich SN, Gleason RE, Williams GH, Muller JE. Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med. 1987 Jun 11;316(24):1514-8. doi: 10.1056/NEJM198706113162405.

    PMID: 3587281BACKGROUND

  • Scheer FA, Michelson AD, Frelinger AL 3rd, Evoniuk H, Kelly EE, McCarthy M, Doamekpor LA, Barnard MR, Shea SA. The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors. PLoS One. 2011;6(9):e24549. doi: 10.1371/journal.pone.0024549. Epub 2011 Sep 8.

    PMID: 21931750BACKGROUND

  • Di Minno G, Silver MJ, Murphy S. Monitoring the entry of new platelets into the circulation after ingestion of aspirin. Blood. 1983 Jun;61(6):1081-5.

    PMID: 6404326BACKGROUND

  • Kriszbacher I, Ajtay Z, Koppan M, Bodis J. Can the time of taking aspirin influence the frequency of cardiovascular events? Am J Cardiol. 2005 Aug 15;96(4):608-10. doi: 10.1016/j.amjcard.2005.03.068. No abstract available.

    PMID: 16098324BACKGROUND

  • Bonten TN, Saris A, van Oostrom MJ, Snoep JD, Rosendaal FR, Zwaginga J, Eikenboom J, van der Meer PF, van der Bom JG. Effect of aspirin intake at bedtime versus on awakening on circadian rhythm of platelet reactivity. A randomised cross-over trial. Thromb Haemost. 2014 Dec;112(6):1209-18. doi: 10.1160/TH14-05-0453. Epub 2014 Sep 11.

    PMID: 25208590DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 12, 2013

First Posted

July 16, 2013

Study Start

July 1, 2013

Primary Completion

January 1, 2014

Study Completion

January 1, 2014

Last Updated

February 20, 2014

Record last verified: 2014-02

Locations

NL(1)