Coronary Artery DiseasePhase 2/3NCT03381742
Efficacy and Safety of Low-dose Ticagrelor
A Phase 2/3 study testing Ticagrelor and clopidogrel in people with Coronary Artery Disease, run by First Affiliated Hospital of Harbin Medical University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Ticagrelor and clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,043 participants
- Where
- 1 siteChina
- Study dates
- 13 Dec 2017to 13 Feb 2019
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with coronary artery disease
Who cannot join
- younger than 18 years of age;
- anti-platelet therapy with clopidogrel or ticagrelor for less than 5 days;
- previous or current treatment with any other potentially confounding drugs.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Different Ticagrelor Regimens Versus Clopidogrel in Patients With Coronary Artery Disease: a Retrospective Multicenter Study (SUPERIOR)
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. One-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than standard dose clopidogrel in Chinese patients with stable CAD. But large-scale clinical trials are still needed to confirm the effects of low-dose ticagrelor on platelet function in Chinese 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.
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. One-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than standard dose clopidogrel in Chinese patients with stable CAD. But large-scale clinical trials are still needed to confirm the effects of low-dose ticagrelor on platelet function in Chinese patients with coronary heart disease.
- Conditions
- Coronary Artery Disease
- Being tested
- Ticagrelor, clopidogrel
- 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.
TicagrelorDrug
ticagrelor 45 mg twice daily for 5 consecutive days at least.
ticagrelorDrug
ticagrelor 90 mg once daily for 5 consecutive days at least.
ticagrelorDrug
ticagrelor 90 mg twice daily for 5 consecutive days at least.
clopidogrelDrug
clopidogrel 75 mg once daily for 5 consecutive days at least.
| Study group | Role | What they receive |
|---|---|---|
| ticagrelor 45mg bidpo. | Experimental | To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Receives: Drug: Ticagrelor |
| ticagrelor 90mg qdpo. | Experimental | To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. Receives: Drug: ticagrelor |
| ticagrelor 90mg bidpo. | Active comparator | To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. Receives: Drug: ticagrelor |
| clopidogrel 75mg qdpo. | Active comparator | To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. Receives: Drug: clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
ADP-induced Inhibition of Platelet Aggregation
The venous blood samples for platelet function test were drawn after an overnight fast, at 12 hours post-last study-drug dose for subjects receiving twice-daily administrations, and at 24 hours post-last study-drug dose for subjects treated with once-daily regimens. The blood was collected in an evacuated vacuum tube containing 3.2% trisodium citrate and lithium heparin. Then the samples were processed within two hours of blood draw according to standard operating procedure. The physical properties of samples were analyzed using Thromboelastography (TEG) Hemostasis Analyzer (CFMS LEPU-8800, Lepu Medical Technology Co., Ltd, Beijing, China) and automated analytical software. TEG test used four channels to detect the effects of anti-platelet therapy via the arachidonic acid (AA) and ADP pathways. TEG test results were expressed in terms of ADP-induced inhibition of platelet aggregation (IPA, range 0% - 100%), with higher values indicating greater platelet inhibition.
Measured: up to 5 days
Number of Participants With Bleeding (Major or Minor Bleeding)
Major bleeding was defined as type ≥ 3 and minor bleeding as types 1 and 2, in accordance to the Bleeding Academic Research Consortium classification. (Mehran R et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449.)
Measured: up to 5 days
Secondary outcomes (4)
ADP-induced Platelet-fibrin Clot Strength (MA)
The physical properties of samples were analyzed using Thromboelastography (TEG) Hemostasis Analyzer (CFMS LEPU-8800, Lepu Medical Technology Co., Ltd, Beijing, China) and automated analytical software. TEG test used four channels to detect the effects of anti-platelet therapy via the arachidonic acid (AA) and ADP pathways. TEG test results were expressed in terms of ADP-induced platelet-fibrin clot strength (MA). A MA>47mm was shown to have a high predictive value for 3-year post-PCI ischemic events during dual antiplatelet therapy. Moreover, ROC curve and quartile analysis suggested MA<31 mm as a predictive value for post-PCI bleeding events (J Am Coll Cardiol. 2013;62(24):2261-73. doi: 10.1016/j.jacc.2013.07.101.).
Measured: up to 5 days
Number of Participants With High On-Treatment Platelet Reactivity (HTPR)
HTPR was defined as IPA ≤ 30% and MA ≥ 47 mm.
Measured: up to 5 days
Number of Participants With Cardiovascular Event (Cardiovascular Death, New-onset Myocardial Infarction, or Stroke)
Cardiovascular death was defined as sudden cardiac death, fatal myocardial infarction, death due to heart failure, or death due to other cardiovascular causes. Stroke was defined as the focal loss of neurologic function caused by an ischemic or a hemorrhagic event with residual symptoms lasting at least 24 hours or eventually leading to death.
Measured: up to 5 days
Number of Participants With New-onset Dyspnea
New-onset dyspnea in patients without previous history of dyspnea
Measured: up to 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2017
- Study start13 Dec 2017
- Primary completion13 Dec 2018
- Study completion13 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 3,043 participants (actual)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Harbin Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Anzhen Hospital, The First Affiliated Hospital of Dalian Medical University, The Central Hospital of Jia Mu Si City, First Affiliated Hospital of Kunming Medical University, RenJi Hospital, Tianjin Medical University General Hospital, Weifang People's Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Shengjing Hospital, Shaanxi Provincial People's Hospital
- Responsible party
- Sponsor
- Investigators
- Yue Li, MD, Principal investigator, Cardiovascular Department, the First Affiliated Hospital of Harbin Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03381742
- Sponsor's protocol ID
- ACS-2
- Status last verified
- Jun 2019
- First submitted
- 14 Dec 2017
- Last updated
- 30 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- 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 30 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Different Ticagrelor Regimens Versus Clopidogrel in Patients With Coronary Artery Disease: a Retrospective Multicenter Study (SUPERIOR)
- ClinicalTrials.gov ID
- NCT03381742
- Acronym / sponsor ID
- ACS-2
- Conditions
- Coronary Artery Disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,043 participants (actual)
- Lead sponsor
- First Affiliated Hospital of Harbin Medical UniversityUniversity, hospital or other
- Collaborators
- Beijing Anzhen Hospital, The First Affiliated Hospital of Dalian Medical University, The Central Hospital of Jia Mu Si City, First Affiliated Hospital of Kunming Medical University, RenJi Hospital, Tianjin Medical University General Hospital, Weifang People's Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Shengjing Hospital, Shaanxi Provincial People's Hospital
- Study start
- 13 Dec 2017 (actual)
- Primary completion
- 13 Dec 2018 (actual)
- Study completion
- 13 Feb 2019 (actual)
- First posted
- 22 Dec 2017 (actual)
- Results
- Posted 30 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. One-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than standard dose clopidogrel in Chinese patients with stable CAD. But large-scale clinical trials are still needed to confirm the effects of low-dose ticagrelor on platelet function in Chinese 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.
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. One-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than standard dose clopidogrel in Chinese patients with stable CAD. But large-scale clinical trials are still needed to confirm the effects of low-dose ticagrelor on platelet function in Chinese patients with coronary heart disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ticagrelor 45mg bidpo. | Experimental | Drug: TicagrelorTo observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. |
| ticagrelor 90mg qdpo. | Experimental | Drug: ticagrelorTo observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. |
| ticagrelor 90mg bidpo. | Active comparator | Drug: ticagrelorTo observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. |
| clopidogrel 75mg qdpo. | Active comparator | Drug: clopidogrelTo observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with coronary artery disease
Key exclusion criteria (3 listed)
- younger than 18 years of age;
- anti-platelet therapy with clopidogrel or ticagrelor for less than 5 days;
- previous or current treatment with any other potentially confounding drugs.
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 |
|---|---|---|
| Ticagrelorticagrelor 45 mg twice daily for 5 consecutive days at least. | Drug | ticagrelor 45mg bidpo. |
| ticagrelorticagrelor 90 mg once daily for 5 consecutive days at least. | Drug | ticagrelor 90mg qdpo. |
| ticagrelorticagrelor 90 mg twice daily for 5 consecutive days at least. | Drug | ticagrelor 90mg bidpo. |
| clopidogrelclopidogrel 75 mg once daily for 5 consecutive days at least. | Drug | clopidogrel 75mg qdpo. |
Primary outcome
ADP-induced Inhibition of Platelet Aggregation
Time frame: up to 5 days
The venous blood samples for platelet function test were drawn after an overnight fast, at 12 hours post-last study-drug dose for subjects receiving twice-daily administrations, and at 24 hours post-last study-drug dose for subjects treated with once-daily regimens. The blood was collected in an evacuated vacuum tube containing 3.2% trisodium citrate and lithium heparin. Then the samples were processed within two hours of blood draw according to standard operating procedure. The physical properties of samples were analyzed using Thromboelastography (TEG) Hemostasis Analyzer (CFMS LEPU-8800, Lepu Medical Technology Co., Ltd, Beijing, China) and automated analytical software. TEG test used four channels to detect the effects of anti-platelet therapy via the arachidonic acid (AA) and ADP pathways. TEG test results were expressed in terms of ADP-induced inhibition of platelet aggregation (IPA, range 0% - 100%), with higher values indicating greater platelet inhibition.
Number of Participants With Bleeding (Major or Minor Bleeding)
Time frame: up to 5 days
Major bleeding was defined as type ≥ 3 and minor bleeding as types 1 and 2, in accordance to the Bleeding Academic Research Consortium classification. (Mehran R et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449.)
4 secondary outcomes
ADP-induced Platelet-fibrin Clot Strength (MA)
Time frame: up to 5 days
Number of Participants With High On-Treatment Platelet Reactivity (HTPR)
Time frame: up to 5 days
Number of Participants With Cardiovascular Event (Cardiovascular Death, New-onset Myocardial Infarction, or Stroke)
Time frame: up to 5 days
Number of Participants With New-onset Dyspnea
Time frame: up to 5 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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, MD principal investigator
Cardiovascular Department, the 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 2/3 study testing Ticagrelor and clopidogrel in people with Coronary Artery Disease, 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 1 inclusion and 3 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 30 Sep 2019. 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 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?
Yes. Results are posted in the registry (first posted 30 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
ADP-induced Inhibition of Platelet Aggregation (time frame: up to 5 days). The study lists 2 primary outcomes in all. 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 30 Sep 2019.