Cardiovascular DiseasesTImE ASPIRINNCT04132791
TIME ASPIRIN: Chronotherapy With Aspirin for Reduction of Cardiovascular Disease
A study of Cardiovascular Diseases, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
This study will be a comparative effectiveness research to determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after awakening and aspirin before bedtime. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiovascular Diseases
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 328 participants
- Where
- 1 siteNetherlands
- Study dates
- 7 Oct 2019to 31 Mar 2022
- Phase
- Interventional
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Use of low-dose aspirin (acetylsalicylic acid 80mg [brand name: acetylsalicylic acid cardio TEVA]~)
- Patients using aspirin from an MDD ('Baxter')
- Capacity to give informed consent (IC)
Who cannot join
- Pregnancy
- Mental or physical disability to fulfil study requirements
- Insufficient knowledge of the Dutch language
- Patients currently participating in another (clinical) trial or study
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Leiden University Medical Center
Leiden, South Holland, 2333 ZA
About this study
Official title: Chronotherapy With Aspirin for Reduction of Cardiovascular Disease
This study will be a comparative effectiveness research to determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after awakening and aspirin before bedtime.
Read the detailed description
Aspirin is the cornerstone of preventive cardiovascular disease (CVD) treatment and bedtime intake of aspirin (chronotherapy) has been shown to reduce morning activity of platelets. It has been shown that platelet reactivity follows a clear circadian rhythm, with a peak of platelet reactivity during the morning (6-12 AM). Importantly, studies have shown in meta-analyses that high platelet activity is predictive of adverse cardiovascular outcomes in patients with stable CVD. Given this knowledge, it is highly likely that the morning peak of platelet reactivity contributes to the morning peak of cardiovascular events and that reduction of morning platelet activity prevents cardiovascular events during morning hours. This may be achieved by intake of aspirin at bedtime instead of on awakening. This study will be a comparative effectiveness research to determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after awakening and aspirin before bedtime.
- Conditions
- Cardiovascular Diseases
- Being tested
- placebo after awakening + aspirin before bedtime, aspirin after awakening + placebo before bedtime
- Keywords
- Aspirin, Chronotherapy
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placebo after awakening + aspirin before bedtimeOther
Also called Acetylsalicylic acid Cardio Teva 80 mg, intake before bedtime
determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after wakening and aspirin before bedtime.
aspirin after awakening + placebo before bedtimeOther
Also called Acetylsalicylic acid Cardio Teva 80 mg, intake after awakening
determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after wakening and aspirin before bedtime.
| Study group | Role | What they receive |
|---|---|---|
| aspirin after awakening + placebo before bedtime | Other | Acetylsalicylic acid 80 mg once daily, orally. Intake in de morning after awakening. Participants already use acetylsalicylic acid 80 mg once daily due to secondary prevention of cardiovascular disease.
Placebo tablet once daily will be added to their medication. The placebo tablet will be taken before bedtime, orally. The placebo is given throughout the study. Receives: Other: aspirin after awakening + placebo before bedtime |
| placebo after awakening +aspirin before bedtime | Experimental | Acetylsalicylic acid 80 mg once daily, orally. The time will be changed form morning to bedtime. Participants already use acetylsalicylic acid 80 mg once daily due to secondary prevention of cardiovascular disease.
Placebo tablet once daily will be added to their medication. The placebo tablet will be taken after awakening, orally. The placebo is given throughout the study. Receives: Other: placebo after awakening + aspirin before bedtime |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rate of major adverse cardiovascular events
the difference in number of participants with a major adverse cardiovascular events, defined as the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, transient ischemic attack, need for repeat revascularízation by redo-CABG or repeat percutaneous intervention.
Measured: maximum of 4 years follow up
Secondary outcomes (3)
Comparing the incidence rate of major cardiovascular events between the two groups in the morning (6-12), evening (12-21) and night (21-6).
It is expected that bedtime aspirin reduces the number of participants with primary outcome (major cardiovascular events) more during morning hours (6-12h) compared with the rest of the day. So we will compare the mornig events, afternoon/evening and night events between the two groups and compare the difference.
Measured: maximum of 4 years follow up
Incidence rate of side-effects between the 2 groups
the difference between the 2 groups of the number of participants that experience side-effects (e.g. bleeding, gastrointestinal symptoms)
Measured: maximum of 4 years follow up
cost-effectiveness of the intervention
Comparing the relative costs and outcomes (effects) between the 2 groups. Data from questionnaire (use of health care) and data from the primary and secondary health care systems. We can compare the use of health care between the two groups en we can calculate the difference in cost between the two groups. So we can estimate if our intervention is cost-effective.
Measured: maximum of 4 years follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2019
- Study start7 Oct 2019
- Primary completion31 Mar 2022
- Study completion31 Mar 2022
Why it stopped: stopped prematurely due to too low inclusion rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- parallel double blinded placebo controlled randomized clinical trial design
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 328 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, tnbonten, Leiden University Medical Center
- Investigators
- Tobias Bonten, Principal investigator, Leiden University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04132791
- Sponsor's protocol ID
- P18.127
- Acronym
- TImE ASPIRIN
- Status last verified
- Jun 2022
- First submitted
- 7 Jun 2019
- Last updated
- 24 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Will be decided in our data management plan
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronotherapy With Aspirin for Reduction of Cardiovascular Disease
- ClinicalTrials.gov ID
- NCT04132791
- Acronym / sponsor ID
- TImE ASPIRIN / P18.127
- Conditions
- Cardiovascular Diseases
- Keywords
- Aspirin, Chronotherapy
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: stopped prematurely due to too low inclusion rate
- Enrolment
- 328 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 7 Oct 2019 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 31 Mar 2022 (actual)
- First posted
- 21 Oct 2019 (actual)
- 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.
This study will be a comparative effectiveness research to determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after awakening and aspirin before bedtime.
Detailed description
Aspirin is the cornerstone of preventive cardiovascular disease (CVD) treatment and bedtime intake of aspirin (chronotherapy) has been shown to reduce morning activity of platelets. It has been shown that platelet reactivity follows a clear circadian rhythm, with a peak of platelet reactivity during the morning (6-12 AM). Importantly, studies have shown in meta-analyses that high platelet activity is predictive of adverse cardiovascular outcomes in patients with stable CVD. Given this knowledge, it is highly likely that the morning peak of platelet reactivity contributes to the morning peak of cardiovascular events and that reduction of morning platelet activity prevents cardiovascular events during morning hours. This may be achieved by intake of aspirin at bedtime instead of on awakening. This study will be a comparative effectiveness research to determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after awakening and aspirin before bedtime.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- parallel double blinded placebo controlled randomized clinical trial design
| Arm | Type | Receives |
|---|---|---|
| aspirin after awakening + placebo before bedtime | Other | Other: aspirin after awakening + placebo before bedtimeAcetylsalicylic acid 80 mg once daily, orally. Intake in de morning after awakening. Participants already use acetylsalicylic acid 80 mg once daily due to secondary prevention of cardiovascular disease. Placebo tablet once daily will be added to their medication. The placebo tablet will be taken before bedtime, orally. The placebo is given throughout the study. |
| placebo after awakening +aspirin before bedtime | Experimental | Other: placebo after awakening + aspirin before bedtimeAcetylsalicylic acid 80 mg once daily, orally. The time will be changed form morning to bedtime. Participants already use acetylsalicylic acid 80 mg once daily due to secondary prevention of cardiovascular disease. Placebo tablet once daily will be added to their medication. The placebo tablet will be taken after awakening, orally. The placebo is given throughout the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Use of low-dose aspirin (acetylsalicylic acid 80mg [brand name: acetylsalicylic acid cardio TEVA]~)
- Patients using aspirin from an MDD ('Baxter')
- Capacity to give informed consent (IC)
Key exclusion criteria (4 listed)
- Pregnancy
- Mental or physical disability to fulfil study requirements
- Insufficient knowledge of the Dutch language
- Patients currently participating in another (clinical) trial or study
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 |
|---|---|---|
| placebo after awakening + aspirin before bedtimeAlso: Acetylsalicylic acid Cardio Teva 80 mg, intake before bedtimedetermine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after wakening and aspirin before bedtime. | Other | placebo after awakening +aspirin before bedtime |
| aspirin after awakening + placebo before bedtimeAlso: Acetylsalicylic acid Cardio Teva 80 mg, intake after awakeningdetermine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after wakening and aspirin before bedtime. | Other | aspirin after awakening + placebo before bedtime |
Primary outcome
Incidence rate of major adverse cardiovascular events
Time frame: maximum of 4 years follow up
the difference in number of participants with a major adverse cardiovascular events, defined as the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, transient ischemic attack, need for repeat revascularízation by redo-CABG or repeat percutaneous intervention.
3 secondary outcomes
Comparing the incidence rate of major cardiovascular events between the two groups in the morning (6-12), evening (12-21) and night (21-6).
Time frame: maximum of 4 years follow up
Incidence rate of side-effects between the 2 groups
Time frame: maximum of 4 years follow up
cost-effectiveness of the intervention
Time frame: maximum of 4 years follow up
Results and safety
The study was stopped early (reason given: stopped prematurely due to too low inclusion rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2022.
- Individual participant dataSharing planned: Undecided. Will be decided in our data management plan
Related trials for Cardiovascular Diseases
Active, not recruitingPhase 3
ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Ischemic Optic Neuropathy
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
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.
Tobias Bonten principal investigator
Leiden University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Cardiovascular Diseases, 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 4 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: stopped early, as of the sponsor's last update on 24 Jun 2022. 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.
Are results available for this study?
The study was stopped early (reason given: stopped prematurely due to too low inclusion rate). Results are not available in the source record.
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?
Incidence rate of major adverse cardiovascular events (time frame: maximum of 4 years follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jun 2022.