Acute Coronary SyndromePhase 4NCT01642238
Antithrombotic Effects of Ticagrelor Versus Clopidogrel
A Phase 4 study testing Ticagrelor + ASA + Bivalirudin and Clopidogrel + ASA + Bivalirudin in people with Acute Coronary Syndrome, run by Juan J Badimon at 1 site in United States.
Trial summary
The purpose of this study is to determine whether treatment with ticagrelor (plus aspirin and bivalirudin) is more effective than treatment with clopidogrel (plus aspirin and bivalirudin). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Coronary Syndrome
- What is being tested?
- Ticagrelor + ASA + Bivalirudin and Clopidogrel + ASA + Bivalirudin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Apr 2013
- Phase
- Phase 4
- 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female volunteers between 18 and 65 years old.
- Body mass index (BMI) 18 - 30 kg/m2 inclusive.
- Healthy as assessed by a detailed medical history and physical examination.
- Laboratory est results within the normal range.
- Ability to provide signed informed consent.
Who cannot join
- History of clinically relevant disease, bleeding, acute infectious disease or signs of acute illness.
- Allergy or hypersensitivity to aspirin or thienopyridines, or atopy diagnosed by a physician.
- Use of medication within one month prior to study drug administration.
- History of drug abuse or alcohol consumption >20 g/day.
- Inability to abstain from intensive muscular effort or sport competition.
- Loss of >400 mL blood or blood donation within 3 months.
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- Positive serology for hepatitis B (HBs Ag) or hepatitis C.
- Conditions associated with hemorrhagic risk.
- Positive pregnancy test.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Randomized, Crossover Study of the Antithrombotic Effects of Ticagrelor Plus Aspirin Versus Clopidogrel Plus Aspirin When Administered With Bivalirudin
The purpose of this study is to determine whether treatment with ticagrelor (plus aspirin and bivalirudin) is more effective than treatment with clopidogrel (plus aspirin and bivalirudin).
Read the detailed description
The HORIZONS-AMI Trial compared the effectiveness of heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin in acute myocardial infarction (AMI) patients undergoing stent deployment 1. Overall the data showed benefits associated with the bivalirudin treatment with lower rates of all-cause mortality, cardiac mortality, re-infarction and non-CABG related major bleeding; However, the data seems to indicate a non-significant increase in acute stent thrombosis in the bivalirudin group. This observation seems to suggest the potential benefits of adding an antiplatelet agent to bivalirudin. A study by Dangas G et al found that in the HORIZONS-AMI patients, the group receiving 600 mg loading-dose of clopidogrel had significantly lower 30-day unadjusted rates of mortality, reinfarction and stent thrombosis than the 300 mg loading-dose group, without increase in bleeding rate. Furthermore, even though the benefits of bivalirudin were independent of the clopidogrel loading dose; the 600mg LD was associated with more benefits with both anticoagulation regimens. Similar observations have been reported in the ARMYDA-6 MI study.
It is our hypothesis that using ticagrelor instead of clopidogrel, given its more potent and faster activity, would have greater antithrombotic activity and therefore may reduce the rate of acute stent thrombosis when administered in combination with bivalirudin + ASA in AMI patients. To investigate this hypothesis, we will compare the antithrombotic effects of ticagrelor with clopidogrel, when administered in combination with ASA and bivalirudin, in healthy human volunteers using a cross-over study design. The antithrombotic activity will be assessed pre-treatment and 2-hours and 24-hours post treatment, using methodologies including Badimon Perfusion chamber, VerifyNow P2Y12 assay, platelet aggregation with Multiplate Analyzer and Thromboelastography.
- Conditions
- Acute Coronary Syndrome
- Being tested
- Ticagrelor + ASA + Bivalirudin, Clopidogrel + ASA + Bivalirudin
- Keywords
- Antiplatelet, ticagrelor, clopidogrel, bivalirudin, thrombosis
- Medical subject headings
- Acute Coronary Syndrome, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ticagrelor + ASA + BivalirudinDrug
Also called Brilinta (ticagrelor, Aspirin (ASA), Angiomax (bivalirudin)
Single loading dose of Ticagrelor (180 mg given as two 90 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
Clopidogrel + ASA + BivalirudinDrug
Also called Plavix (clopidogrel), Aspirin (ASA), Angiomax (bivalirudin)
Single loading dose of Clopidogrel (600 mg given as two 300 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor + ASA + Bivalirudin | Experimental | Single loading dose of Ticagrelor (180 mg given as two 90 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour. Receives: Drug: Ticagrelor + ASA + Bivalirudin |
| Clopidogrel + ASA + Bivalirudin | Active comparator | Single loading dose of Clopidogrel (600 mg given as two 300 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour. Receives: Drug: Clopidogrel + ASA + Bivalirudin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
Change in thrombus size at 1 hour as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
Measured: Pre-treatment baseline and 1 hour
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
Change in thrombus size at 24 hours as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
Measured: Pre-treatment baseline and 24 hrs post treatment
Secondary outcomes (6)
Platelet Reactivity
Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
Measured: Pre-treatment baseline
Platelet Reactivity
Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
Measured: 1 hr post-treatment
Platelet Reactivity
Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
Measured: 24-hours post-treatment
Blood Thrombogenicity
Coagulation times, assessed using the ROTEM thromboelastometry
Measured: Pre-treatment baseline
Blood Thrombogenicity
Coagulation times, assessed using the ROTEM thromboelastometry
Measured: 1 hr post-treatment
Blood Thrombogenicity
Coagulation times, assessed using the ROTEM thromboelastometry
Measured: 24-hours post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionMar 2013
- Study completionApr 2013
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Juan J Badimon
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor-investigator, Juan J Badimon, Icahn School of Medicine at Mount Sinai
- Investigators
- Juan J Badimon, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01642238
- Sponsor's protocol ID
- GCO 12-0732
- Other IDs
- ISSBRIL0067
- Status last verified
- Jun 2016
- First submitted
- 13 Jul 2012
- Last updated
- 11 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Zafar MU, Vorchheimer DA, Tewar MP, Giannarelli C, Crippa M, Sartori S, Rodriguez D, Baber U, Mehran R, Badimon JJ. Ticagrelor reduces thrombus formation more than clopidogrel, even when co-administered with bivalirudin. Thromb Haemost. 2014 Nov;112(5):1069-70. doi: 10.1160/TH14-03-0269. Epub 2014 Aug 7. No abstract available.
PubMed 25104302
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Crossover Study of the Antithrombotic Effects of Ticagrelor Plus Aspirin Versus Clopidogrel Plus Aspirin When Administered With Bivalirudin
- ClinicalTrials.gov ID
- NCT01642238
- Acronym / sponsor ID
- GCO 12-0732
- Conditions
- Acute Coronary Syndrome
- Keywords
- Antiplatelet, ticagrelor, clopidogrel, bivalirudin, thrombosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Juan J BadimonUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Jul 2012
- Primary completion
- Mar 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 17 Jul 2012 (estimated)
- Results
- Posted 11 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether treatment with ticagrelor (plus aspirin and bivalirudin) is more effective than treatment with clopidogrel (plus aspirin and bivalirudin).
Detailed description
The HORIZONS-AMI Trial compared the effectiveness of heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin in acute myocardial infarction (AMI) patients undergoing stent deployment 1. Overall the data showed benefits associated with the bivalirudin treatment with lower rates of all-cause mortality, cardiac mortality, re-infarction and non-CABG related major bleeding; However, the data seems to indicate a non-significant increase in acute stent thrombosis in the bivalirudin group. This observation seems to suggest the potential benefits of adding an antiplatelet agent to bivalirudin. A study by Dangas G et al found that in the HORIZONS-AMI patients, the group receiving 600 mg loading-dose of clopidogrel had significantly lower 30-day unadjusted rates of mortality, reinfarction and stent thrombosis than the 300 mg loading-dose group, without increase in bleeding rate. Furthermore, even though the benefits of bivalirudin were independent of the clopidogrel loading dose; the 600mg LD was associated with more benefits with both anticoagulation regimens. Similar observations have been reported in the ARMYDA-6 MI study.
It is our hypothesis that using ticagrelor instead of clopidogrel, given its more potent and faster activity, would have greater antithrombotic activity and therefore may reduce the rate of acute stent thrombosis when administered in combination with bivalirudin + ASA in AMI patients. To investigate this hypothesis, we will compare the antithrombotic effects of ticagrelor with clopidogrel, when administered in combination with ASA and bivalirudin, in healthy human volunteers using a cross-over study design. The antithrombotic activity will be assessed pre-treatment and 2-hours and 24-hours post treatment, using methodologies including Badimon Perfusion chamber, VerifyNow P2Y12 assay, platelet aggregation with Multiplate Analyzer and Thromboelastography.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor + ASA + Bivalirudin | Experimental | Drug: Ticagrelor + ASA + BivalirudinSingle loading dose of Ticagrelor (180 mg given as two 90 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour. |
| Clopidogrel + ASA + Bivalirudin | Active comparator | Drug: Clopidogrel + ASA + BivalirudinSingle loading dose of Clopidogrel (600 mg given as two 300 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female volunteers between 18 and 65 years old.
- Body mass index (BMI) 18 - 30 kg/m2 inclusive.
- Healthy as assessed by a detailed medical history and physical examination.
- Laboratory est results within the normal range.
- Ability to provide signed informed consent.
Key exclusion criteria (9 listed)
- History of clinically relevant disease, bleeding, acute infectious disease or signs of acute illness.
- Allergy or hypersensitivity to aspirin or thienopyridines, or atopy diagnosed by a physician.
- Use of medication within one month prior to study drug administration.
- History of drug abuse or alcohol consumption >20 g/day.
- Inability to abstain from intensive muscular effort or sport competition.
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 + ASA + BivalirudinAlso: Brilinta (ticagrelor, Aspirin (ASA), Angiomax (bivalirudin)Single loading dose of Ticagrelor (180 mg given as two 90 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour. | Drug | Ticagrelor + ASA + Bivalirudin |
| Clopidogrel + ASA + BivalirudinAlso: Plavix (clopidogrel), Aspirin (ASA), Angiomax (bivalirudin)Single loading dose of Clopidogrel (600 mg given as two 300 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour. | Drug | Clopidogrel + ASA + Bivalirudin |
Primary outcome
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
Time frame: Pre-treatment baseline and 1 hour
Change in thrombus size at 1 hour as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
Time frame: Pre-treatment baseline and 24 hrs post treatment
Change in thrombus size at 24 hours as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
6 secondary outcomes
Platelet Reactivity
Time frame: Pre-treatment baseline
Platelet Reactivity
Time frame: 1 hr post-treatment
Platelet Reactivity
Time frame: 24-hours post-treatment
Blood Thrombogenicity
Time frame: Pre-treatment baseline
Blood Thrombogenicity
Time frame: 1 hr post-treatment
Blood Thrombogenicity
Time frame: 24-hours post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25104302Zafar MU, Vorchheimer DA, Tewar MP, Giannarelli C, Crippa M, Sartori S, Rodriguez D, Baber U, Mehran R, Badimon JJ. Ticagrelor reduces thrombus formation more than clopidogrel, even when co-administered with bivalirudin. Thromb Haemost. 2014 Nov;112(5):1069-70. doi: 10.1160/TH14-03-0269. Epub 2014 Aug 7. No abstract available.
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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.
Juan J Badimon, PhD principal investigator
Icahn School of Medicine at Mount Sinai
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 + ASA + Bivalirudin and Clopidogrel + ASA + Bivalirudin in people with Acute Coronary Syndrome, run by Juan J Badimon 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 5 inclusion and 9 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 11 Jul 2016. 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 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?
Yes. Results are posted in the registry (first posted 11 Jul 2016). 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?
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis (time frame: Pre-treatment baseline and 1 hour). 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?
On the ClinicalTrials.gov record for NCT01642238, 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 11 Jul 2016.