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Aspirin AM or PM: Effect on Circadian Rhythm of Platelet Reactivity

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ClinicalTrials.gov Identifier: NCT01900639
Recruitment Status : Completed
First Posted : July 16, 2013
Last Update Posted : February 20, 2014
Sponsor:
Information provided by (Responsible Party):
Leiden University Medical Center

Tracking Information
First Submitted Date  ICMJE July 12, 2013
First Posted Date  ICMJE July 16, 2013
Last Update Posted Date February 20, 2014
Study Start Date  ICMJE July 2013
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 12, 2013)
Circadian rhythm of platelet reactivity [ Time Frame: 24hour rhythm of platelet reactivity ]
Platelet reactivity will be measured by VerifyNow-aspirin assay, serum thromboxane B2, and flow-cytometry.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01900639 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Aspirin AM or PM: Effect on Circadian Rhythm of Platelet Reactivity
Official Title  ICMJE Effect of Aspirin Intake on Awakening Versus at Bedtime on Circadian Rhythm of Platelet Reactivity in Healthy Subjects
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.
Detailed Description

Cardiovascular events are a leading cause of mortality and morbidity in western countries. In the European Union, 47% of total mortality is caused by cardiovascular disease2. Aspirin is a cornerstone in the secondary prevention of cardiovascular disease because of its inhibitory effects on platelet aggregation. It reduces the risk of recurrent cardiovascular events with about a quarter3. Although not supported by evidence, aspirin is usually taken in the morning, but it may be more beneficial to take aspirin at bedtime instead of on awakening. It has been convincingly shown that platelet activity follows a circadian rhythm, with a peak of platelet reactivity in the morning4-8. This might in part explain the increase in cardiovascular events in the early morning, with the highest incidence between 6 and 12 AM1.

Since platelet reactivity follows a circadian rhythm, the timing of aspirin intake may influence its inhibitory effect on platelets. Due to its short half-life, aspirin only inhibits platelets which are present at the time of intake. New platelets are released at a rate of 10%/day, predominantly during the night9. Because they are more reactive and not inhibited by aspirin taken in the preceding morning, these young platelets contribute to the morning peak of platelet reactivity10, 11. It has been argued that intake of aspirin at bedtime could better prevent the early morning increase in platelet reactivity than intake on awakening, assuming that intake on awakening would be too late to prevent this morning peak in platelet reactivity12. Additionally, a recent study showed significant recovery of platelet aggregation after 24 hours in patients using low-dose aspirin on a daily basis13. This supports the hypothesis that aspirin intake at bedtime could be beneficial in reducing the morning peak of platelet reactivity, thereby possibly also reducing the incidence of arterial thrombotic events in the morning. However, this has never been studied before.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Aspirin
  • Circadian Rhythm
  • Platelet Activation
  • Cardiovascular Diseases
Intervention  ICMJE Behavioral: change time of intake of aspirin
Study Arms  ICMJE
  • Active Comparator: aspirin on awakening
    intake of 80 acetylsalicylic acid on awakening for 2 weeks
    Intervention: Behavioral: change time of intake of aspirin
  • Experimental: aspirin at bedtime
    intake of 80mg acetylsalicylic acis at bedtime
    Intervention: Behavioral: change time of intake of aspirin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 12, 2013)
14
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2014
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01900639
Other Study ID Numbers  ICMJE NL.44378.058.13
2013-001410-16 ( EudraCT Number )
P13.092 ( Other Identifier: Leiden University Medical Center )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Leiden University Medical Center
Study Sponsor  ICMJE Leiden University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Leiden University Medical Center
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP