Platelet ReactivityPhase 4NCT03614832
Ticagrelor and Clopidogrel on Platelet Aggregation in Clopidogrel Resistance's Patients With CHD
A Phase 4 study testing Ticagrelor 90 mg and Clopidogrel 150 mg in people with Platelet Reactivity, run by First Affiliated Hospital of Harbin Medical University at 1 site in China.
Trial summary
The study sought to observe the effects of optimal dose of ticagrelor（90 mg qd）ticagrelor and double standard-dose clopidogrel on platelet reactivity in coronary heart disease patients with high on-treatment platelet reactivity (HTPR) while on clopidogrel. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Platelet Reactivity
- What is being tested?
- Ticagrelor 90 mg and Clopidogrel 150 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2018to 1 Oct 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with coronary heart disease (CHD) ;
- Patients with high on-treatment platelet reactivity (HTPR) while on clopidogrel. Meet the one standards of the following:
- The platelet aggregation rate (PAgR) measured with light transmission aggregometry (LTA) is decreased no more than 10% from baseline level, or PAgR is more than 46%; (2) The percentage of inhibition of ADP-induced platelet aggregation measured by thrombelastogram is not more than 30%; (3) The PRU of inhibition of ADP-induced platelet aggregation measured by VerifyNow >208.
Who cannot join
- 1.Severe lung injury; 2.Planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, or anticoagulant therapy during the study period; 3.Platelet count <100g/L; 4.Creatinine clearance rate < 30ml/min; 5.Severe liver injury. 6.Diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive heart failure NYHA II-IV or left ventricular ejection fraction < 40%); 7.A history of bleeding tendency; 8.Aspirin, ticagrelor or clopidogrel allergies;
- -
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
the first affiliated hospital of Harbin medical university
Harbin, Heilongjiang, 150001
Yue Li, PhD
About this study
Official title: Optimal Dose of Ticagrelor（90 mg qd）and Double Standard-dose Clopidogrel on Platelet Aggregation in Clopidogrel Resistance's Patients With Coronary Heart Disease
The study sought to observe the effects of optimal dose of ticagrelor（90 mg qd）ticagrelor and double standard-dose clopidogrel on platelet reactivity in coronary heart disease patients with high on-treatment platelet reactivity (HTPR) while on clopidogrel.
HTPR with clopidogrel administration in coronary heart disease (CHD) patients has associated with an increased risk of adverse events. Newer P2Y12 inhibitors ticagrelor (90mg BID) provide stronger platelet inhibition compared with clopidogrel, but a low-dose of ticagrelor (90mg QD) has not been previously studied in Chinese CHD patients with HTPR.
Read the detailed description
Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 receptor inhibitor has been the mainstay for the prevention of recurrent ischemic events in ACS patients and in those undergoing PCI. However, clopidogrel shows major individual variation in its antiplatelet effect in association with an increased incidence of ischemic events and stent thrombosis in patients with High on-treatment platelet reactivity (HTPR). There are several possible mechanisms of clopidogrel response variability or "resistance". Recently, it has been reported that a marked decrease in platelet response to clopidogrel is highly associated with the CYP2C19*2 loss-of-function allele, leading to an adverse prognosis.
Ticagrelor is the first reversibly binding, oral, direct acting P2Y12 receptor antagonist. Increasing studies showed that ticagrelor has a more rapid onset of effect and greater inhibition of platelet aggregation compared with clopidogrel. Recently, it has been reported that low-dose ticagrelor either with 90 mg QD or 45 mg BID, was associated with a more potent antiplatelet effect compared with clopidogrel treatment and once daily dose provided similar antiplatelet effect but favorable effect on optimal platelet inhibition compared with twice daily dose. Hiasa et al. identified that ticagrelor 45 mg twice daily was associated with enhanced inhibition of platelet aggregation (IPA) compared with clopidogrel 75 mg once daily in 118 Japanese patients with stable CAD. 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. Therefore, the optimal dose of ticagrelor for Chinese patients with HTPR is increasingly urgent.
So the objectives of this clinical study were to evaluate the effects of optimal dose of ticagrelor（90 mg qd）ticagrelor and double standard-dose clopidogrel on platelet reactivity in Chinese CHD patients with HTPR.
- Conditions
- Platelet Reactivity
- Being tested
- Ticagrelor 90 mg, Clopidogrel 150 mg
- Keywords
- ticagrelor, clopidogrel, platelet reactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ticagrelor 90 mgDrug
half-dose ticagrelor treatment (90 mg loading dose, then 90 mg once daily) for 1 week.
Clopidogrel 150 mgDrug
double standard-dose clopidogrel treatment (150 mg loading dose, then 150 mg once daily) for 1 week.
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor 90 mg | Experimental | To observe low-dose of ticagrelor（90 mg once daily oral）on platelet aggregation in clopidogrel resistance's patients with coronary heart disease. Receives: Drug: Ticagrelor 90 mg |
| Clopidogrel 150 mg | Active comparator | To observe double standard-dose clopidogrel （150 mg once daily oral）on platelet aggregation in clopidogrel resistance's patients with coronary heart disease. Receives: Drug: Clopidogrel 150 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
The plateletinhibition ratio.
Thromboelastography (TEG) was used to measure platelet inhibition ratio.
Measured: up to 7 days
Secondary outcomes (1)
The platelet aggregation ratio.
Light transmission aggregometry method was used to measure platelet aggregation
Measured: up to 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2018
- Study start1 May 2018
- Primary completion1 May 2019 (estimated)
- Study completion1 Oct 2019 (estimated)
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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Harbin Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yue Li, PhD, Principal investigator, First Affiliated Hospital of Harbin Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03614832
- Sponsor's protocol ID
- CHD-201802
- Status last verified
- Feb 2018
- First submitted
- 3 Jul 2018
- Last updated
- 3 Aug 2018
- 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 3 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Dose of Ticagrelor（90 mg qd）and Double Standard-dose Clopidogrel on Platelet Aggregation in Clopidogrel Resistance's Patients With Coronary Heart Disease
- ClinicalTrials.gov ID
- NCT03614832
- Acronym / sponsor ID
- CHD-201802
- Conditions
- Platelet Reactivity
- Keywords
- ticagrelor, clopidogrel, platelet reactivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Harbin Medical UniversityUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 1 May 2019 (estimated)
- Study completion
- 1 Oct 2019 (estimated)
- First posted
- 3 Aug 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.
The study sought to observe the effects of optimal dose of ticagrelor（90 mg qd）ticagrelor and double standard-dose clopidogrel on platelet reactivity in coronary heart disease patients with high on-treatment platelet reactivity (HTPR) while on clopidogrel.
HTPR with clopidogrel administration in coronary heart disease (CHD) patients has associated with an increased risk of adverse events. Newer P2Y12 inhibitors ticagrelor (90mg BID) provide stronger platelet inhibition compared with clopidogrel, but a low-dose of ticagrelor (90mg QD) has not been previously studied in Chinese CHD patients with HTPR.
Detailed description
Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 receptor inhibitor has been the mainstay for the prevention of recurrent ischemic events in ACS patients and in those undergoing PCI. However, clopidogrel shows major individual variation in its antiplatelet effect in association with an increased incidence of ischemic events and stent thrombosis in patients with High on-treatment platelet reactivity (HTPR). There are several possible mechanisms of clopidogrel response variability or "resistance". Recently, it has been reported that a marked decrease in platelet response to clopidogrel is highly associated with the CYP2C19*2 loss-of-function allele, leading to an adverse prognosis.
Ticagrelor is the first reversibly binding, oral, direct acting P2Y12 receptor antagonist. Increasing studies showed that ticagrelor has a more rapid onset of effect and greater inhibition of platelet aggregation compared with clopidogrel. Recently, it has been reported that low-dose ticagrelor either with 90 mg QD or 45 mg BID, was associated with a more potent antiplatelet effect compared with clopidogrel treatment and once daily dose provided similar antiplatelet effect but favorable effect on optimal platelet inhibition compared with twice daily dose. Hiasa et al. identified that ticagrelor 45 mg twice daily was associated with enhanced inhibition of platelet aggregation (IPA) compared with clopidogrel 75 mg once daily in 118 Japanese patients with stable CAD. 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. Therefore, the optimal dose of ticagrelor for Chinese patients with HTPR is increasingly urgent.
So the objectives of this clinical study were to evaluate the effects of optimal dose of ticagrelor（90 mg qd）ticagrelor and double standard-dose clopidogrel on platelet reactivity in Chinese CHD patients with HTPR.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor 90 mg | Experimental | Drug: Ticagrelor 90 mgTo observe low-dose of ticagrelor（90 mg once daily oral）on platelet aggregation in clopidogrel resistance's patients with coronary heart disease. |
| Clopidogrel 150 mg | Active comparator | Drug: Clopidogrel 150 mgTo observe double standard-dose clopidogrel （150 mg once daily oral）on platelet aggregation in clopidogrel resistance's patients with coronary heart disease. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with coronary heart disease (CHD) ;
- Patients with high on-treatment platelet reactivity (HTPR) while on clopidogrel. Meet the one standards of the following:
- The platelet aggregation rate (PAgR) measured with light transmission aggregometry (LTA) is decreased no more than 10% from baseline level, or PAgR is more than 46%; (2) The percentage of inhibition of ADP-induced platelet aggregation measured by thrombelastogram is not more than 30%; (3) The PRU of inhibition of ADP-induced platelet aggregation measured by VerifyNow >208.
Key exclusion criteria (2 listed)
- 1.Severe lung injury; 2.Planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, or anticoagulant therapy during the study period; 3.Platelet count <100g/L; 4.Creatinine clearance rate < 30ml/min; 5.Severe liver injury. 6.Diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive heart failure NYHA II-IV or left ventricular ejection fraction < 40%); 7.A history of bleeding tendency; 8.Aspirin, ticagrelor or clopidogrel allergies;
- -
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 |
|---|---|---|
| Ticagrelor 90 mghalf-dose ticagrelor treatment (90 mg loading dose, then 90 mg once daily) for 1 week. | Drug | Ticagrelor 90 mg |
| Clopidogrel 150 mgdouble standard-dose clopidogrel treatment (150 mg loading dose, then 150 mg once daily) for 1 week. | Drug | Clopidogrel 150 mg |
Primary outcome
The plateletinhibition ratio.
Time frame: up to 7 days
Thromboelastography (TEG) was used to measure platelet inhibition ratio.
1 secondary outcome
The platelet aggregation ratio.
Time frame: up to 7 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2018.
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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, PhD 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 Ticagrelor 90 mg and Clopidogrel 150 mg 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 3 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 3 Aug 2018. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guangzhong Liu, PhD (86-451-85555672, lgz2700@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The plateletinhibition ratio. (time frame: up to 7 days). 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 3 Aug 2018.