AspirinPhase 4NCT01900639
Aspirin AM or PM: Effect on Circadian Rhythm of Platelet Reactivity
A Phase 4 study testing change time of intake of aspirin in people with Aspirin and Circadian Rhythm, run by Leiden University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Aspirin, Circadian Rhythm, Platelet Activation
- What is being tested?
- change time of intake of aspirin
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteNetherlands
- Study dates
- Jul 2013to Jan 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy subject
- Age >18yrs
- Capacity to give informed consent (IC)
Who cannot join
- 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)
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Aspirin Intake on Awakening Versus at Bedtime on Circadian Rhythm of Platelet Reactivity in Healthy Subjects
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.
Read the 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.
- Being tested
- change time of intake of aspirin
- Keywords
- aspirin, circadian rhythm, platelet reactivity, platelet activation, time dependent
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
change time of intake of aspirinBehavioural
| Study group | Role | What they receive |
|---|---|---|
| aspirin on awakening | Active comparator | intake of 80 acetylsalicylic acid on awakening for 2 weeks Receives: Behavioral: change time of intake of aspirin |
| aspirin at bedtime | Experimental | intake of 80mg acetylsalicylic acis at bedtime Receives: Behavioral: change time of intake of aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Circadian rhythm of platelet reactivity
Platelet reactivity will be measured by VerifyNow-aspirin assay, serum thromboxane B2, and flow-cytometry.
Measured: 24hour rhythm of platelet reactivity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for AspirinStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01900639
- Sponsor's protocol ID
- NL.44378.058.13
- Other IDs
- 2013-001410-16, P13.092
- Status last verified
- Feb 2014
- First submitted
- 12 Jul 2013
- Last updated
- 20 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 3587281Scheer 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.
PubMed 21931750Di 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.
PubMed 6404326Kriszbacher 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.
PubMed 16098324Bonten 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.
PubMed 25208590
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Aspirin Intake on Awakening Versus at Bedtime on Circadian Rhythm of Platelet Reactivity in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01900639
- Acronym / sponsor ID
- NL.44378.058.13
- Keywords
- aspirin, circadian rhythm, platelet reactivity, platelet activation, time dependent
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 16 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| aspirin on awakening | Active comparator | Behavioral: change time of intake of aspirinintake of 80 acetylsalicylic acid on awakening for 2 weeks |
| aspirin at bedtime | Experimental | Behavioral: change time of intake of aspirinintake of 80mg acetylsalicylic acis at bedtime |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Healthy subject
- Age >18yrs
- Capacity to give informed consent (IC)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| change time of intake of aspirin | Behavioural | aspirin at bedtime, aspirin on awakening |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2014.
- Background: PubMed 3587281Tofler 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.
- Background: PubMed 21931750Scheer 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.
- Background: PubMed 6404326Di 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.
- Background: PubMed 16098324Kriszbacher 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.
- Derived from this study: PubMed 25208590Bonten 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.
Related trials for Aspirin
RecruitingPhase 3
REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants
Symptomatic Venous Thromboembolism (VTE)
RecruitingPhase 2
A Phase IIa Randomized, Double-Blinded Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome
T Cells, Colorectal Cancer
Active, not recruitingPhase 2/3
Regorafenib With Low-dose Chemotherapies and Aspirin Followed by Standard Chemotherapies in Metastatic Colorectal Cancer
Metastatic Colorectal Cancer
RecruitingPhase 3
The Efficacy of Aspirin Combined With Hydroxychloroquine Treatment in High Risk Pregnancies for Preeclampsia
Preeclampsia
Not yet recruitingPhase 3
Aspirin for the Prevention of Ischemic Complications in Giant Cell Arteritis
Giant Cell Arteritis (GCA), Acute Coronary Syndrome (ACS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing change time of intake of aspirin in people with Aspirin and Circadian Rhythm, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Circadian rhythm of platelet reactivity (time frame: 24hour rhythm of platelet reactivity). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01900639, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2014.