Coronary Artery DiseasePhase 2/3NCT03062462
Half-dose Ticagrelor Overcomes High-dose Clopidogrel in Acute Coronary Syndrome Patients With High On-Clopidogrel Platelet Reactivity
A Phase 2/3 study testing Clopidogrel and ticagrelor in people with Coronary Artery Disease and Clopidogrel, Poor Metabolism of, run by First Affiliated Hospital of Harbin Medical University at 1 site in United States.
Trial summary
With the widespread use of clopidogrel, resistance to clopidogrel has been attracting increasing attention, and emerged as a new challenge adversely affecting patients clinical risk and outcome. Clopidogrel resistance means that blood platelets show little or no response to clopidogrel. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Coronary Artery Disease, Clopidogrel, Poor Metabolism of
- What is being tested?
- Clopidogrel and ticagrelor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2017to 31 Dec 2019
- Phase
- Phase 2/3
- 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 oral clopidogrel treatment admitted to hospital within 24 hours or long-term follow-up outpatients with oral clopidogrel treatment;
- 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% and the percentage of inhibition of ADP-induced platelet aggregation measured by thrombelastogram is not more than 30%;
Who cannot join
- Planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, or anticoagulant therapy during the study period;
- Platelet count <100g/L;
- 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;
- Aspirin, ticagrelor or clopidogrel allergies;
- Severe liver injury.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
whole blood lumi-aggregometer type 560 VS
Havertown, Pennsylvania, 19083
Chongyang Zhang, MM, 1330640@qq.com
About this study
With the widespread use of clopidogrel, resistance to clopidogrel has been attracting increasing attention, and emerged as a new challenge adversely affecting patients clinical risk and outcome. Clopidogrel resistance means that blood platelets show little or no response to clopidogrel. It is closely associated with increased risk of serious cardiovascular events, seriously affects the prognosis of patients, and brings difficulties to clinical treatment.
Guideline recommendations on the use of dual antiplatelet therapy have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular events. The previous studies have reported that half-dose ticagrelor had the similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was significantly stronger than that in the clopidogrel group. But it is still not very clear that the effect of low-dose ticagrelor on platelet function in patients with clopidogrel resistance and coronary heart disease.
Therefore, we performed this randomized, single-blind clinical trial to observe the effects of low-dose ticagrelor and double standard-dose clopidogrel on platelet aggregation and prognosis in clopidogrel resistance's patients with coronary heart disease.
Read the detailed description
Dual Antiplatelet Therapy (DAPT) with aspirin and P2Y12 receptor inhibitor remains a cornerstone in the secondary prevention of coronary artery disease (CAD). Clopidogrel is one of the most commonly used antithrombotic agent that inhibits the platelet P2Y(12) adenosine diphosphate (ADP) receptor. With the widespread use of clopidogrel, resistance to clopidogrel has been attracting increasing attention, and emerged as a new challenge adversely affecting patients clinical risk and outcome. Clopidogrel resistance means that blood platelets show little or no response to clopidogrel. Recent studies have found that clopidogrel resistance rate was about 11% ~ 44%. Clopidogrel resistance is more common in patients with loss-of-function CYP2C19 genotypes, and closely associated with increased risk of serious cardiovascular events, including ischemic events, myocardial infarction, stent thrombosis, revascularization and so on. This seriously affects the prognosis of patients, and brings difficulties to clinical treatment.
Ticagrelor is an oral, reversibly-binding, direct-acting P2Y12 receptor antagonist used clinically for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS). Guideline recommendations on the use of dual antiplatelet therapy have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular events. The previous studies have reported that half-dose ticagrelor had the similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was significantly stronger than that in the clopidogrel group. But it is still not very clear that the effect of low-dose ticagrelor on platelet function in patients with clopidogrel resistance and coronary heart disease.
Therefore, we performed this randomized, single-blind clinical trial to observe the effects of low-dose ticagrelor and double standard-dose clopidogrel on platelet aggregation and cardiovascular prognosis in clopidogrel resistance's patients with coronary heart disease.
- Being tested
- Clopidogrel, ticagrelor
- 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.
ClopidogrelDrug
double standard-dose clopidogrel treatment (300 mg loading dose, then 75 mg twice daily) for 5-7 days
ticagrelorDrug
half-dose ticagrelor treatment (90 mg loading dose, then 45 mg twice daily) for 5-7 days
| Study group | Role | What they receive |
|---|---|---|
| clopidogrel | Active comparator | To observe double standard-dose clopidogrel on platelet aggregation in clopidogrel resistance's patients with coronary heart disease Receives: Drug: Clopidogrel |
| ticagrelor | Experimental | To observe low-dose of ticagrelor on platelet aggregation in clopidogrel resistance's patients with coronary heart disease Receives: Drug: ticagrelor |
What is being measured
The primary outcome is the main question the study is designed to answer.
The platelet aggregation rate
Light transmission aggregometry method
Measured: up to 7 days
Secondary outcomes (2)
Side effects including bleeding,dyspnea and arrhythmia
Measured: up to 7 days, 1 month, 3 months, 6 months and 12 months
Adverse events including myocardial infarction, death, stroke, re-hospitalization for cardiovascular diseases and ischemia events
Measured: up to 7 days, 1 month, 3 months, 6 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2017
- Study start10 Feb 2017
- Primary completion31 Jul 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Harbin Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03062462
- Sponsor's protocol ID
- SCAD-20170220
- Status last verified
- Feb 2018
- First submitted
- 20 Feb 2017
- Last updated
- 7 May 2018
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Liu GZ, Zhang S, Sun DH, Shi J, Bo WL, Wang WN, Zhang CY, Wang ZH, Feng W, He MJ, Liu YY, Li S, Zheng LQ, Li Y. Half-dose ticagrelor versus high-dose clopidogrel in reducing platelet reactivity in acute coronary syndrome patients with high on-clopidogrel platelet reactivity (divide study). Eur J Clin Pharmacol. 2019 Aug;75(8):1059-1068. doi: 10.1007/s00228-019-02687-0. Epub 2019 May 12.
PubMed 31081522
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Half-dose Ticagrelor Overcomes High-dose Clopidogrel in Acute Coronary Syndrome Patients With High On-Clopidogrel Platelet Reactivity
- ClinicalTrials.gov ID
- NCT03062462
- Acronym / sponsor ID
- SCAD-20170220
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Harbin Medical UniversityUniversity, hospital or other
- Study start
- 10 Feb 2017 (actual)
- Primary completion
- 31 Jul 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 23 Feb 2017 (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.
With the widespread use of clopidogrel, resistance to clopidogrel has been attracting increasing attention, and emerged as a new challenge adversely affecting patients clinical risk and outcome. Clopidogrel resistance means that blood platelets show little or no response to clopidogrel. It is closely associated with increased risk of serious cardiovascular events, seriously affects the prognosis of patients, and brings difficulties to clinical treatment.
Guideline recommendations on the use of dual antiplatelet therapy have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular events. The previous studies have reported that half-dose ticagrelor had the similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was significantly stronger than that in the clopidogrel group. But it is still not very clear that the effect of low-dose ticagrelor on platelet function in patients with clopidogrel resistance and coronary heart disease.
Therefore, we performed this randomized, single-blind clinical trial to observe the effects of low-dose ticagrelor and double standard-dose clopidogrel on platelet aggregation and prognosis in clopidogrel resistance's patients with coronary heart disease.
Detailed description
Dual Antiplatelet Therapy (DAPT) with aspirin and P2Y12 receptor inhibitor remains a cornerstone in the secondary prevention of coronary artery disease (CAD). Clopidogrel is one of the most commonly used antithrombotic agent that inhibits the platelet P2Y(12) adenosine diphosphate (ADP) receptor. With the widespread use of clopidogrel, resistance to clopidogrel has been attracting increasing attention, and emerged as a new challenge adversely affecting patients clinical risk and outcome. Clopidogrel resistance means that blood platelets show little or no response to clopidogrel. Recent studies have found that clopidogrel resistance rate was about 11% ~ 44%. Clopidogrel resistance is more common in patients with loss-of-function CYP2C19 genotypes, and closely associated with increased risk of serious cardiovascular events, including ischemic events, myocardial infarction, stent thrombosis, revascularization and so on. This seriously affects the prognosis of patients, and brings difficulties to clinical treatment.
Ticagrelor is an oral, reversibly-binding, direct-acting P2Y12 receptor antagonist used clinically for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS). Guideline recommendations on the use of dual antiplatelet therapy have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular events. The previous studies have reported that half-dose ticagrelor had the similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was significantly stronger than that in the clopidogrel group. But it is still not very clear that the effect of low-dose ticagrelor on platelet function in patients with clopidogrel resistance and coronary heart disease.
Therefore, we performed this randomized, single-blind clinical trial to observe the effects of low-dose ticagrelor and double standard-dose clopidogrel on platelet aggregation and cardiovascular prognosis in clopidogrel resistance's patients with coronary heart disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| clopidogrel | Active comparator | Drug: ClopidogrelTo observe double standard-dose clopidogrel on platelet aggregation in clopidogrel resistance's patients with coronary heart disease |
| ticagrelor | Experimental | Drug: ticagrelorTo observe low-dose of ticagrelor 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 (2 listed)
- Patients with oral clopidogrel treatment admitted to hospital within 24 hours or long-term follow-up outpatients with oral clopidogrel treatment;
- 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% and the percentage of inhibition of ADP-induced platelet aggregation measured by thrombelastogram is not more than 30%;
Key exclusion criteria (7 listed)
- Planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, or anticoagulant therapy during the study period;
- Platelet count <100g/L;
- 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;
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 |
|---|---|---|
| Clopidogreldouble standard-dose clopidogrel treatment (300 mg loading dose, then 75 mg twice daily) for 5-7 days | Drug | clopidogrel |
| ticagrelorhalf-dose ticagrelor treatment (90 mg loading dose, then 45 mg twice daily) for 5-7 days | Drug | ticagrelor |
Primary outcome
The platelet aggregation rate
Time frame: up to 7 days
Light transmission aggregometry method
2 secondary outcomes
Side effects including bleeding,dyspnea and arrhythmia
Time frame: up to 7 days, 1 month, 3 months, 6 months and 12 months
Adverse events including myocardial infarction, death, stroke, re-hospitalization for cardiovascular diseases and ischemia events
Time frame: up to 7 days, 1 month, 3 months, 6 months and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2018.
- Derived from this study: PubMed 31081522Liu GZ, Zhang S, Sun DH, Shi J, Bo WL, Wang WN, Zhang CY, Wang ZH, Feng W, He MJ, Liu YY, Li S, Zheng LQ, Li Y. Half-dose ticagrelor versus high-dose clopidogrel in reducing platelet reactivity in acute coronary syndrome patients with high on-clopidogrel platelet reactivity (divide study). Eur J Clin Pharmacol. 2019 Aug;75(8):1059-1068. doi: 10.1007/s00228-019-02687-0. Epub 2019 May 12.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Clopidogrel and ticagrelor in people with Coronary Artery Disease and Clopidogrel, Poor Metabolism of, run by First Affiliated Hospital of Harbin Medical University at 1 site in United States.
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 2 inclusion and 7 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 7 May 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 United States. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 platelet aggregation rate (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?
On the ClinicalTrials.gov record for NCT03062462, which also lists 1 linked publication.
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 7 May 2018.