Non ST Segment Elevation Acute Coronary SyndromePhase 3NCT02415803
Safety and Efficacy of Low-Dose Ticagrelor in Chinese Patients With NSTE-ACS
A Phase 3 study testing low-dose ticagrelor, conventional-dose ticagrelor and Clopidogrel in people with Non ST Segment Elevation Acute Coronary Syndrome, run by First Affiliated Hospital of Harbin Medical University at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non ST Segment Elevation Acute Coronary Syndrome
- What is being tested?
- low-dose ticagrelor, conventional-dose ticagrelor and Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to Dec 2016
- Phase
- Phase 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
- hospitalized for NSTE-ACS within the preceding 48 h
- have one of the following additional criteria:
- ischemic symptoms at rest, lasting ≥10 minutes;
- horizontal or down-sloping ST segment depression ≥0.1 mV;
- cardiac troponin I (cTnI), marker associated with NSTE-ACS, local laboratory upper limit of normal values;
- underwent percutaneous coronary intervention (PCI); (5) a history of myocardial infarction.
Who cannot join
- ST-elevation ACS;
- 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;
- diabetes.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
VerifyNow
San Diego, California, 92101-92117
Jing Shi, MM, 518-393-2200, customerservice@accriva.com
About this study
Official title: Safety and Efficacy of Low-Dose Ticagrelor in Chinese Patients With Non-ST-Elevation Acute Coronary Syndrome: A Randomized Clinical Trial
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 (DAPT) have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for patients who have an ACS with or without ST-segment elevation. These recommendations are primarily based on large, randomized, Phase III clinical trials. However, few East Asian patients (or those of East Asian descent) have been included in these trials to assess the use of these drugs. In addition, a growing body of data supported that East Asian might have different adverse event profiles (thrombophilia and bleeding) and "therapeutic window" compared with white subjects. Furthermore, "East Asian paradox" phenomenon has been described that East Asian patients have a higher prevalence of platelet reactivity during DAPT, but an ischaemic event rate following PCI or ACS is similar or even lower than white patients. Therefore, the antiplatelet treatment strategy that is most appropriate for East Asian patients is increasingly urgent. Therefore, we performed the current study to observe the different effects of low-dose ticagrelor (45 mg twice daily), conventional-dose ticagrelor (90 mg twice daily) and clopidogrel (75mg once daily) on high platelet reactivity (HPR) and IPA, and investigated the safety and efficacy of low-dose ticagrelor further in Chinese patients with non-ST-elevation ACS (NSTE-ACS).
Read the detailed description
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 (DAPT) have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for patients who have an ACS with or without ST-segment elevation. These recommendations are primarily based on large, randomized, Phase III clinical trials. However, few East Asian patients (or those of East Asian descent) have been included in these trials to assess the use of these drugs. In addition, a growing body of data supported that East Asian might have different adverse event profiles (thrombophilia and bleeding) and "therapeutic window" compared with white subjects. Furthermore, "East Asian paradox" phenomenon has been described that East Asian patients have a higher prevalence of platelet reactivity during DAPT, but an ischaemic event rate following PCI or ACS is similar or even lower than white patients. Therefore, the antiplatelet treatment strategy that is most appropriate for East Asian patients is increasingly urgent. In Korea and Japan, it has been reported that low doses of ticagrelor had a more potent inhibition of platelet aggregation (IPA) than clopidogrel (75 mg once daily) in healthy subjects and patients with stable coronary artery disease, respectively. But it is still not clear whether a low dose of ticagrelor is superior to clopidogrel in a large population of Chinese ACS patients. A recent study on pharmacokinetics and tolerability of ticagrelor has found that maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) 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. This data also suggested that a low dose of ticagrelor might be more appropriate for Chinese ACS patients. In view of a large diurnal variation with a single daily dose, a lower dose twice daily may be a better choice for Chinese patients. Therefore, we performed the current study to observe the different effects of low-dose ticagrelor (45 mg twice daily), conventional-dose ticagrelor (90 mg twice daily) and clopidogrel (75mg once daily) on high platelet reactivity (HPR) and IPA, and investigated the safety and efficacy of low-dose ticagrelor further in Chinese patients with non-ST-elevation ACS (NSTE-ACS).
- Being tested
- low-dose ticagrelor, conventional-dose ticagrelor, Clopidogrel
- Keywords
- low-dose ticagrelor, clopidogrel, Chinese patients with NSTE-ACS, platelet reactivity, inhibition of platelet aggregation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
low-dose ticagrelorDrug
90 mg loading dose, then 45 mg twice daily for 5 days
conventional-dose ticagrelorDrug
180 mg loading dose, then 90 mg twice daily for 5 days
ClopidogrelDrug
300 mg loading dose, then 75 mg once daily for 5 days
| Study group | Role | What they receive |
|---|---|---|
| low-dose ticagrelor | Experimental | To observe the safety and efficacy of low-dose ticagrelor in Chinese patients with non-ST-elevation acute coronary syndrome Receives: Drug: low-dose ticagrelor |
| conventional-dose ticagrelor | Active comparator | To observe the different safety and efficacy between low-dose ticagrelor and conventional-dose ticagrelor. Receives: Drug: conventional-dose ticagrelor |
| clopidogrel | Active comparator | To observe the different safety and efficacy between low-dose ticagrelor and conventional-dose clopidogrel. Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
the differences in mean inhibition of platelet aggregation or inhibition ratio (%)
After overnight fasting, venous blood samples of all subjects were taken for pharmacodynamic measurements before dosing (baseline) and 12 hours after the last dose. VerifyNow P2Y12 (Accumetrics, SanDiego, CA), a whole-blood, cartridge-based and point-of-care turbidometric assay, was performed to test platelet aggregation at baseline and 12 hours after the last dose, and the results were reported in P2Y12 reaction units (PRU). With this assay, a higher PRU reflects greater adenosine-diphosphate-mediated platelet reactivity (PR). High-platelet reactivity (HPR) was defined as a PRU>208. Blood samples were placed in 3.2% sodium citrate (Greiner Bio-One Vacuette North America, Inc, Monroe, NC) for this assay. Additionally, inhibition of platelet aggregation (IPA) calculated by VerifyNow assays was similar to light transmittance aggregometry.
Measured: before dosing (baseline) and up to 12 hours after the last dose
Secondary outcomes (7)
Number of bleeding events
Measured: throughout the study (from baseline to 12 hours after the last dose)
Number of difficulty breathing events
Measured: throughout the study (from baseline to 12 hours after the last dose)
number of ventricular pauses
Measured: throughout the study (from baseline to 12 hours after the last dose)
number of myocardial infarction events
Measured: throughout the study (from baseline to 12 hours after the last dose)
number of death events
Measured: throughout the study (from baseline to 12 hours after the last dose)
number of stroke events
Measured: throughout the study (from baseline to 12 hours after the last dose)
number of severe recurrent ischemia events
Measured: throughout the study (from baseline to 12 hours after the last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2015 (estimated)
- Study startDec 2014
- Primary completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non ST Segment Elevation Acute Coronary SyndromeStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 75 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
- NCT02415803
- Sponsor's protocol ID
- ACS-1
- Status last verified
- Dec 2014
- First submitted
- 26 Mar 2015
- Last updated
- 14 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Low-Dose Ticagrelor in Chinese Patients With Non-ST-Elevation Acute Coronary Syndrome: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02415803
- Acronym / sponsor ID
- ACS-1
- Keywords
- low-dose ticagrelor, clopidogrel, Chinese patients with NSTE-ACS, platelet reactivity, inhibition of platelet aggregation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Harbin Medical UniversityUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Dec 2016 (estimated)
- First posted
- 14 Apr 2015 (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.
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 (DAPT) have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for patients who have an ACS with or without ST-segment elevation. These recommendations are primarily based on large, randomized, Phase III clinical trials. However, few East Asian patients (or those of East Asian descent) have been included in these trials to assess the use of these drugs. In addition, a growing body of data supported that East Asian might have different adverse event profiles (thrombophilia and bleeding) and "therapeutic window" compared with white subjects. Furthermore, "East Asian paradox" phenomenon has been described that East Asian patients have a higher prevalence of platelet reactivity during DAPT, but an ischaemic event rate following PCI or ACS is similar or even lower than white patients. Therefore, the antiplatelet treatment strategy that is most appropriate for East Asian patients is increasingly urgent. Therefore, we performed the current study to observe the different effects of low-dose ticagrelor (45 mg twice daily), conventional-dose ticagrelor (90 mg twice daily) and clopidogrel (75mg once daily) on high platelet reactivity (HPR) and IPA, and investigated the safety and efficacy of low-dose ticagrelor further in Chinese patients with non-ST-elevation ACS (NSTE-ACS).
Detailed description
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 (DAPT) have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for patients who have an ACS with or without ST-segment elevation. These recommendations are primarily based on large, randomized, Phase III clinical trials. However, few East Asian patients (or those of East Asian descent) have been included in these trials to assess the use of these drugs. In addition, a growing body of data supported that East Asian might have different adverse event profiles (thrombophilia and bleeding) and "therapeutic window" compared with white subjects. Furthermore, "East Asian paradox" phenomenon has been described that East Asian patients have a higher prevalence of platelet reactivity during DAPT, but an ischaemic event rate following PCI or ACS is similar or even lower than white patients. Therefore, the antiplatelet treatment strategy that is most appropriate for East Asian patients is increasingly urgent. In Korea and Japan, it has been reported that low doses of ticagrelor had a more potent inhibition of platelet aggregation (IPA) than clopidogrel (75 mg once daily) in healthy subjects and patients with stable coronary artery disease, respectively. But it is still not clear whether a low dose of ticagrelor is superior to clopidogrel in a large population of Chinese ACS patients. A recent study on pharmacokinetics and tolerability of ticagrelor has found that maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) 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. This data also suggested that a low dose of ticagrelor might be more appropriate for Chinese ACS patients. In view of a large diurnal variation with a single daily dose, a lower dose twice daily may be a better choice for Chinese patients. Therefore, we performed the current study to observe the different effects of low-dose ticagrelor (45 mg twice daily), conventional-dose ticagrelor (90 mg twice daily) and clopidogrel (75mg once daily) on high platelet reactivity (HPR) and IPA, and investigated the safety and efficacy of low-dose ticagrelor further in Chinese patients with non-ST-elevation ACS (NSTE-ACS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| low-dose ticagrelor | Experimental | Drug: low-dose ticagrelorTo observe the safety and efficacy of low-dose ticagrelor in Chinese patients with non-ST-elevation acute coronary syndrome |
| conventional-dose ticagrelor | Active comparator | Drug: conventional-dose ticagrelorTo observe the different safety and efficacy between low-dose ticagrelor and conventional-dose ticagrelor. |
| clopidogrel | Active comparator | Drug: ClopidogrelTo observe the different safety and efficacy between low-dose ticagrelor and conventional-dose clopidogrel. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- hospitalized for NSTE-ACS within the preceding 48 h
- have one of the following additional criteria:
Key exclusion criteria (8 listed)
- ST-elevation ACS;
- 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%);
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 ticagrelor90 mg loading dose, then 45 mg twice daily for 5 days | Drug | low-dose ticagrelor |
| conventional-dose ticagrelor180 mg loading dose, then 90 mg twice daily for 5 days | Drug | conventional-dose ticagrelor |
| Clopidogrel300 mg loading dose, then 75 mg once daily for 5 days | Drug | clopidogrel |
Primary outcome
the differences in mean inhibition of platelet aggregation or inhibition ratio (%)
Time frame: before dosing (baseline) and up to 12 hours after the last dose
After overnight fasting, venous blood samples of all subjects were taken for pharmacodynamic measurements before dosing (baseline) and 12 hours after the last dose. VerifyNow P2Y12 (Accumetrics, SanDiego, CA), a whole-blood, cartridge-based and point-of-care turbidometric assay, was performed to test platelet aggregation at baseline and 12 hours after the last dose, and the results were reported in P2Y12 reaction units (PRU). With this assay, a higher PRU reflects greater adenosine-diphosphate-mediated platelet reactivity (PR). High-platelet reactivity (HPR) was defined as a PRU>208. Blood samples were placed in 3.2% sodium citrate (Greiner Bio-One Vacuette North America, Inc, Monroe, NC) for this assay. Additionally, inhibition of platelet aggregation (IPA) calculated by VerifyNow assays was similar to light transmittance aggregometry.
7 secondary outcomes
Number of bleeding events
Time frame: throughout the study (from baseline to 12 hours after the last dose)
Number of difficulty breathing events
Time frame: throughout the study (from baseline to 12 hours after the last dose)
number of ventricular pauses
Time frame: throughout the study (from baseline to 12 hours after the last dose)
number of myocardial infarction events
Time frame: throughout the study (from baseline to 12 hours after the last dose)
number of death events
Time frame: throughout the study (from baseline to 12 hours after the last dose)
number of stroke events
Time frame: throughout the study (from baseline to 12 hours after the last dose)
number of severe recurrent ischemia events
Time frame: throughout the study (from baseline to 12 hours after the last dose)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2015.
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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 3 study testing low-dose ticagrelor, conventional-dose ticagrelor and Clopidogrel in people with Non ST Segment Elevation Acute Coronary Syndrome, 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 6 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: status not confirmed, as of the sponsor's last update on 14 Apr 2015. 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 phase mean?
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 Yue Li, MD (86-451-85555673, ly99ly@vip.163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the differences in mean inhibition of platelet aggregation or inhibition ratio (%) (time frame: before dosing (baseline) and up to 12 hours after the last dose). 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 14 Apr 2015.