Platelet ReactivityPhase 4NCT03679091
Low-dose of Ticagrelor and Standard-dose Clopidogrel on Platelet Effects in Chinese Patients With Stable CAD.
A Phase 4 study testing low-dose ticagrelor and Clopidogrel in people with Platelet Reactivity, run by First Affiliated Hospital of Harbin Medical University at 1 site in China.
Trial summary
Ticagrelor has been demonstrated to provide a more rapid and more powerful inhibition of platelet aggregation compared with clopidogrel in coronary artery disease (CAD) patients. However, current guidelines recommend ticagrelor 90 mg twice daily might not be suitable for patients of Chinese. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Platelet Reactivity
- What is being tested?
- low-dose ticagrelor and Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 29 Aug 2018to 28 Feb 2019
- 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 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients were eligible to participate if they were aged ≥18 years and ≤ 75 Years
- Subjects had documented stable CAD (defned as stable angina pectoris and objective evidence of CAD, a previous MI, or previous revascularization with percutaneous coronary intervention or coronary artery bypass grafting)
- Women were required to be postmenopausal or surgically sterile
- Patients who were taking clopidogrel or ticagrelor were required to discontinue these agents at least 14 days before randomization
Who cannot join
- Acute coronary syndrome (ACS)
- planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists other than the study medication, or anticoagulant therapy during the study period
- platelet count <10*10^4/ul
- creatinine clearance rate < 30ml/min
- diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive heart failure NYHA II-IV or left ventricular ejection fraction < 40%)
- a history of bleeding tendency
- allergy to aspirin, ticagrelor or clopidogrel
- diabetes patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Low-dose of Ticagrelor and Standard-dose Clopidogrel on Platelet Effects in Chinese Patients With Stable Coronary Artery Disease: a Randomized, Single-blind, Crossover Clinical Study
Ticagrelor has been demonstrated to provide a more rapid and more powerful inhibition of platelet aggregation compared with clopidogrel in coronary artery disease (CAD) patients. However, current guidelines recommend ticagrelor 90 mg twice daily might not be suitable for patients of Chinese. Therefore, the investigators performed this study to observe the efficacy of 60-mg ticagrelor in comparison to 75-mg clopidogrel in Chinese patients with stable CAD.
Read the detailed description
Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the established standard of care in ACS patients. Although a popular P2Y12 receptor inhibitor, clopidogrel is not the most potent antiplatelet agent due to its metabolic activation. Metabolic activation of clopidogrel depends on multiple cytochrome P450 (CYP) enzymes, including CYP2C19, which can delay the onset of its activity; in addition, some populations carry a reduced-function allele of the CYP2C19 gene. Notably, poor drug metabolism of clopidogrel is more common in Asian populations compared with other international regions, due to the prevalence of CYP2C19 reduced-function alleles in these patients. A recent study indicated that Asians might have different adverse event profiles (thrombophilia and bleeding) and "therapeutic window" compared with white subjects, suggesting that regional differences may influence the altered response of clopidogrel to the onset of thrombotic events.
Ticagrelor is an orally administered, reversibly-binding, direct-acting P2Y12 receptor antagonist used clinically for the prevention of atherothrombotic events in patients with ACS. Guidelines give a recommendation on the use of dual antiplatelet therapy (DAPT) support ticagrelor 90 mg twice daily over clopidogrel 75 mg daily in addition to aspirin in ACS patients with or without ST-segment elevation. Increasing evidence indicated that Asian patients showed higher active metabolite exposure rates and stronger pharmacodynamic responses than their Caucasian subjects when treated with the same oral doses of prasugrel .In Korea and Japan, it has been reported that low doses of ticagrelor might have a more potent inhibition of platelet aggregation (IPA) than clopidogrel in healthy subjects and patients with stable coronary artery disease, respectively .In our previous study, the investigators found that half-dose ticagrelor produced similar inhibitory effects on platelet aggregation as standard-dose ticagrelor and exerted significantly stronger effects than clopidogrel in patients with ACS and one-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than clopidogrel in patients with stable CAD. Furthermore, standard-dose ticagrelor (180mg loading dose [LD], then 90mg twice daily) has a significant increase in the risk of bleeding and incidence rate of dyspnea, and that higher discontinuation rates due to adverse effects compared to clopidogrel. A recent study demonstrated that maximum plasma concentration and area under the plasma concentration-time curve of ticagrelor (90 mg twice daily) and its active metabolite (AR-C124910XX) tended to be approximately 40% higher in healthy Chinese volunteers compared with Caucasian subjects. Notably, poor drug metabolism of clopidogrel is more common in Asian populations compared with other international regions, due to the prevalence of CYP2C19 reduced-function alleles. The data suggested that a low dose of ticagrelor might be more appropriate for Chinese patients.
The objectives of this study were to evaluate the effects of ticagrelor (60.0mg daily) in comparison to clopidogrel (75mg daily) on platelet reactivity in Chinese patients with stable CAD.
- Conditions
- Platelet Reactivity
- Being tested
- low-dose ticagrelor, Clopidogrel
- Keywords
- Ticagrelor, clopidogrel, coronary artery disease, platelet reactivity
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
low-dose ticagrelorDrug
low-dose ticagrelor (60.0 mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of clopidogrel (75mg once daily).
ClopidogrelDrug
clopidogrel (75mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of low-dose ticagrelor (60.0 mg once daily).
| Study group | Role | What they receive |
|---|---|---|
| low-dose ticagrelor | Experimental | To observe the safety and efficacy of low-dose ticagrelor in Chinese patients with Stable Coronary Artery Disease Receives: Drug: low-dose ticagrelor; Drug: Clopidogrel |
| clopidogrel | Active comparator | To observe the safety and efficacy between low-dose ticagrelor and standard-dose clopidogrel. Receives: Drug: low-dose ticagrelor; Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
The platelet inhibition ratio.
Verifynow was used to measure platelet inhibition ratio.
Measured: up to 2 months
Secondary outcomes (1)
The platelet aggregation ratio.
Light transmission aggregometry method was used to measure platelet aggregation ratio.
Measured: up to 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2018
- Study start29 Aug 2018
- Primary completion28 Feb 2019
- Study completion28 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Platelet ReactivityStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Harbin Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yue LI, First Affiliated Hospital of Harbin Medical University
- Investigators
- Yue Li, professor, Principal investigator, First Affiliated Hospital of Harbin Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03679091
- Sponsor's protocol ID
- CHD-201845
- Status last verified
- Dec 2021
- First submitted
- 4 Sep 2018
- Last updated
- 21 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-dose of Ticagrelor and Standard-dose Clopidogrel on Platelet Effects in Chinese Patients With Stable Coronary Artery Disease: a Randomized, Single-blind, Crossover Clinical Study
- ClinicalTrials.gov ID
- NCT03679091
- Acronym / sponsor ID
- CHD-201845
- Conditions
- Platelet Reactivity
- Keywords
- Ticagrelor, clopidogrel, coronary artery disease, platelet reactivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- First Affiliated Hospital of Harbin Medical UniversityUniversity, hospital or other
- Study start
- 29 Aug 2018 (actual)
- Primary completion
- 28 Feb 2019 (actual)
- Study completion
- 28 Feb 2019 (actual)
- First posted
- 20 Sep 2018 (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.
Ticagrelor has been demonstrated to provide a more rapid and more powerful inhibition of platelet aggregation compared with clopidogrel in coronary artery disease (CAD) patients. However, current guidelines recommend ticagrelor 90 mg twice daily might not be suitable for patients of Chinese. Therefore, the investigators performed this study to observe the efficacy of 60-mg ticagrelor in comparison to 75-mg clopidogrel in Chinese patients with stable CAD.
Detailed description
Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the established standard of care in ACS patients. Although a popular P2Y12 receptor inhibitor, clopidogrel is not the most potent antiplatelet agent due to its metabolic activation. Metabolic activation of clopidogrel depends on multiple cytochrome P450 (CYP) enzymes, including CYP2C19, which can delay the onset of its activity; in addition, some populations carry a reduced-function allele of the CYP2C19 gene. Notably, poor drug metabolism of clopidogrel is more common in Asian populations compared with other international regions, due to the prevalence of CYP2C19 reduced-function alleles in these patients. A recent study indicated that Asians might have different adverse event profiles (thrombophilia and bleeding) and "therapeutic window" compared with white subjects, suggesting that regional differences may influence the altered response of clopidogrel to the onset of thrombotic events.
Ticagrelor is an orally administered, reversibly-binding, direct-acting P2Y12 receptor antagonist used clinically for the prevention of atherothrombotic events in patients with ACS. Guidelines give a recommendation on the use of dual antiplatelet therapy (DAPT) support ticagrelor 90 mg twice daily over clopidogrel 75 mg daily in addition to aspirin in ACS patients with or without ST-segment elevation. Increasing evidence indicated that Asian patients showed higher active metabolite exposure rates and stronger pharmacodynamic responses than their Caucasian subjects when treated with the same oral doses of prasugrel .In Korea and Japan, it has been reported that low doses of ticagrelor might have a more potent inhibition of platelet aggregation (IPA) than clopidogrel in healthy subjects and patients with stable coronary artery disease, respectively .In our previous study, the investigators found that half-dose ticagrelor produced similar inhibitory effects on platelet aggregation as standard-dose ticagrelor and exerted significantly stronger effects than clopidogrel in patients with ACS and one-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than clopidogrel in patients with stable CAD. Furthermore, standard-dose ticagrelor (180mg loading dose [LD], then 90mg twice daily) has a significant increase in the risk of bleeding and incidence rate of dyspnea, and that higher discontinuation rates due to adverse effects compared to clopidogrel. A recent study demonstrated that maximum plasma concentration and area under the plasma concentration-time curve of ticagrelor (90 mg twice daily) and its active metabolite (AR-C124910XX) tended to be approximately 40% higher in healthy Chinese volunteers compared with Caucasian subjects. Notably, poor drug metabolism of clopidogrel is more common in Asian populations compared with other international regions, due to the prevalence of CYP2C19 reduced-function alleles. The data suggested that a low dose of ticagrelor might be more appropriate for Chinese patients.
The objectives of this study were to evaluate the effects of ticagrelor (60.0mg daily) in comparison to clopidogrel (75mg daily) on platelet reactivity in Chinese patients with stable CAD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| low-dose ticagrelor | Experimental | Drug: low-dose ticagrelor, Drug: ClopidogrelTo observe the safety and efficacy of low-dose ticagrelor in Chinese patients with Stable Coronary Artery Disease |
| clopidogrel | Active comparator | Drug: low-dose ticagrelor, Drug: ClopidogrelTo observe the safety and efficacy between low-dose ticagrelor and standard-dose clopidogrel. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients were eligible to participate if they were aged ≥18 years and ≤ 75 Years
- Subjects had documented stable CAD (defned as stable angina pectoris and objective evidence of CAD, a previous MI, or previous revascularization with percutaneous coronary intervention or coronary artery bypass grafting)
- Women were required to be postmenopausal or surgically sterile
- Patients who were taking clopidogrel or ticagrelor were required to discontinue these agents at least 14 days before randomization
Key exclusion criteria (8 listed)
- Acute coronary syndrome (ACS)
- planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists other than the study medication, or anticoagulant therapy during the study period
- platelet count <10*10^4/ul
- creatinine clearance rate < 30ml/min
- diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive heart failure NYHA II-IV or left ventricular ejection fraction < 40%)
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 |
|---|---|---|
| low-dose ticagrelorlow-dose ticagrelor (60.0 mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of clopidogrel (75mg once daily). | Drug | clopidogrel, low-dose ticagrelor |
| Clopidogrelclopidogrel (75mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of low-dose ticagrelor (60.0 mg once daily). | Drug | clopidogrel, low-dose ticagrelor |
Primary outcome
The platelet inhibition ratio.
Time frame: up to 2 months
Verifynow was used to measure platelet inhibition ratio.
1 secondary outcome
The platelet aggregation ratio.
Time frame: up to 2 months
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 21 Dec 2021.
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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.
Yue Li, professor principal investigator
First Affiliated Hospital of Harbin Medical University
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 low-dose ticagrelor and Clopidogrel in people with Platelet Reactivity, run by First Affiliated Hospital of Harbin Medical University at 1 site in China.
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 4 inclusion and 8 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 21 Dec 2021. 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 China. 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?
The platelet inhibition ratio. (time frame: up to 2 months). 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 21 Dec 2021.