Coronary Artery DiseasePhase 2NCT01898442
High Ticagrelor Loading Dose in STEMI
A Phase 2 study testing Ticagrelor 180mg, Ticagrelor 270mg and Ticagrelor 360mg in people with Coronary Artery Disease, run by University of Florida at 1 site in United States.
Trial summary
Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Ticagrelor 180mg, Ticagrelor 270mg and Ticagrelor 360mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Jun 2014
- Phase
- Phase 2
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with ST-elevation myocardial infarction undergoing primary PCI.
- Age between 18 and 80 years old.
Who cannot join
- History of prior intracranial bleeding.
- On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 30 days.
- Known allergies to aspirin or ticagrelor.
- On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban).
- Treatment with IIb/IIIa glycoprotein inhibitors.
- Fibrinolytics within 24 hours
Show all 17Show fewer
- Known blood dyscrasia or bleeding diathesis.
- Known platelet count <80x106/mL.
- Known hemoglobin <10 g/dL.
- Active bleeding.
- Hemodynamic instability.
- Known creatinine clearance <30 mL/minute.
- Known severe hepatic dysfunction.
- Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
- Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.
- Pregnant females*.
- Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacodynamic Profiles of Ticagrelor in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Different Loading Dosage Regimens
Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients. However, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects.
Read the detailed description
Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the cornerstone of treatment for prevention of thrombotic events in patients with acute coronary syndromes (ACS). Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events, including cardiovascular mortality. Ticagrelor was recently approved for clinical use in ACS patients, at a dose of 180 mg loading dose and 90 mg twice/day maintenance dose. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients, including those presenting with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). However, there are discordant data on the onset of its antiplatelet effects in this particular setting. In particular, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. However, if the administration of a higher ticagrelor loading dose may overcome this limitation is still unknown and represents the aim of our study. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects. This study will provide insights on the pharmacodynamic effects of higher ticagrelor loading doses and will help clinicians choose the most appropriate treatment to avoid complications related to inadequate platelet inhibition in the early phase of patients with STEMI undergoing primary PCI.
- Conditions
- Coronary Artery Disease
- Being tested
- Ticagrelor 180mg, Ticagrelor 270mg, Ticagrelor 360mg
- Keywords
- platelet function, ticagrelor, STEMI
- Medical subject headings
- Coronary Artery Disease, ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ticagrelor 180mgDrug
Also called Brilinta
Rndomization to standard or high ticagrelor loading dose regimens
Ticagrelor 270mgDrug
Also called Brilinta
Randomization to standard or high loading dose regimen
Ticagrelor 360mgDrug
Also called Brilinta
Randomization to standrad or high loading dose regimen
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor 180 | Active comparator | Standard ticagrelor 180mg loading dose Receives: Drug: Ticagrelor 180mg |
| Ticagrelor 270mg | Experimental | High ticagrelor 270mg loading dose Receives: Drug: Ticagrelor 270mg |
| Ticagrelor 360mg | Experimental | High ticagrelor 360mg loading dose Receives: Drug: Ticagrelor 360mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet Reactivity by VerifyNow P2Y12
The primary end-point of the study was the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 1 hour after administration
Measured: 1 hour
Secondary outcomes (5)
Platelet Reactivity by VerifyNow P2Y12 at Other Time Points
Secondary outcomes included the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 30 min and 2, 4, 8, 24 hours after ticagrelor loading dose administration
Measured: 30 min and 2, 4, 8, 24 hours
Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points
Secondary outcomes included the comparison of the platelet reactivity index (PRI) determined by vasodilator-stimulated phosphoprotein (VASP) at 30 min and 1, 2, 4, 8, 24 hours after ticagrelor loading dose administration
Measured: 30 min and 1, 2, 4, 8, 24 hours
Pharmacokinetic Profiles of Ticagrelor (Tmax)
Pharmacokinetic assessments included determination of plasma concentration of ticagrelor. Time for the maximum plasma concentration (Tmax), maximum observed plasma concentration (Cmax) and the area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) were calculated.
Measured: 24 hours
Pharmacokinetic Profiles of Ticagrelor (Cmax)
Pharmacokinetic assessments included determination of plasma concentration of ticagrelor. Time for the maximum plasma concentration (Tmax), maximum observed plasma concentration (Cmax) and the area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) were calculated.
Measured: 24 hours
Pharmacokinetic Profiles of Ticagrelor (AUC0-t)
Pharmacokinetic assessments included determination of plasma concentration of ticagrelor. Time for the maximum plasma concentration (Tmax), maximum observed plasma concentration (Cmax) and the area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) were calculated.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2013 (estimated)
- Study startSep 2013
- Primary completionJun 2014
- Study completionJun 2014
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 Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dominick Angiolillo, MD, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01898442
- Sponsor's protocol ID
- TicagSTEMI
- Status last verified
- Jun 2014
- First submitted
- 1 Jul 2013
- Last updated
- 8 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Franchi F, Rollini F, Cho JR, Bhatti M, DeGroat C, Ferrante E, Dunn EC, Nanavati A, Carraway E, Suryadevara S, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ. Impact of Escalating Loading Dose Regimens of Ticagrelor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results of a Prospective Randomized Pharmacokinetic and Pharmacodynamic Investigation. JACC Cardiovasc Interv. 2015 Sep;8(11):1457-1467. doi: 10.1016/j.jcin.2015.02.030.
PubMed 26404199
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamic Profiles of Ticagrelor in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Different Loading Dosage Regimens
- ClinicalTrials.gov ID
- NCT01898442
- Acronym / sponsor ID
- TicagSTEMI
- Conditions
- Coronary Artery Disease
- Keywords
- platelet function, ticagrelor, STEMI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 12 Jul 2013 (estimated)
- Results
- Posted 8 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients. However, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects.
Detailed description
Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the cornerstone of treatment for prevention of thrombotic events in patients with acute coronary syndromes (ACS). Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events, including cardiovascular mortality. Ticagrelor was recently approved for clinical use in ACS patients, at a dose of 180 mg loading dose and 90 mg twice/day maintenance dose. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients, including those presenting with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). However, there are discordant data on the onset of its antiplatelet effects in this particular setting. In particular, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. However, if the administration of a higher ticagrelor loading dose may overcome this limitation is still unknown and represents the aim of our study. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects. This study will provide insights on the pharmacodynamic effects of higher ticagrelor loading doses and will help clinicians choose the most appropriate treatment to avoid complications related to inadequate platelet inhibition in the early phase of patients with STEMI undergoing primary PCI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor 180 | Active comparator | Drug: Ticagrelor 180mgStandard ticagrelor 180mg loading dose |
| Ticagrelor 270mg | Experimental | Drug: Ticagrelor 270mgHigh ticagrelor 270mg loading dose |
| Ticagrelor 360mg | Experimental | Drug: Ticagrelor 360mgHigh ticagrelor 360mg loading dose |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with ST-elevation myocardial infarction undergoing primary PCI.
- Age between 18 and 80 years old.
Key exclusion criteria (17 listed)
- History of prior intracranial bleeding.
- On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 30 days.
- Known allergies to aspirin or ticagrelor.
- On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban).
- Treatment with IIb/IIIa glycoprotein inhibitors.
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 180mgAlso: BrilintaRndomization to standard or high ticagrelor loading dose regimens | Drug | Ticagrelor 180 |
| Ticagrelor 270mgAlso: BrilintaRandomization to standard or high loading dose regimen | Drug | Ticagrelor 270mg |
| Ticagrelor 360mgAlso: BrilintaRandomization to standrad or high loading dose regimen | Drug | Ticagrelor 360mg |
Primary outcome
Platelet Reactivity by VerifyNow P2Y12
Time frame: 1 hour
The primary end-point of the study was the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 1 hour after administration
5 secondary outcomes
Platelet Reactivity by VerifyNow P2Y12 at Other Time Points
Time frame: 30 min and 2, 4, 8, 24 hours
Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points
Time frame: 30 min and 1, 2, 4, 8, 24 hours
Pharmacokinetic Profiles of Ticagrelor (Tmax)
Time frame: 24 hours
Pharmacokinetic Profiles of Ticagrelor (Cmax)
Time frame: 24 hours
Pharmacokinetic Profiles of Ticagrelor (AUC0-t)
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26404199Franchi F, Rollini F, Cho JR, Bhatti M, DeGroat C, Ferrante E, Dunn EC, Nanavati A, Carraway E, Suryadevara S, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ. Impact of Escalating Loading Dose Regimens of Ticagrelor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results of a Prospective Randomized Pharmacokinetic and Pharmacodynamic Investigation. JACC Cardiovasc Interv. 2015 Sep;8(11):1457-1467. doi: 10.1016/j.jcin.2015.02.030.
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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.
Dominick Angiolillo, MD, PhD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ticagrelor 180mg, Ticagrelor 270mg and Ticagrelor 360mg in people with Coronary Artery Disease, run by University of Florida 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 17 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 8 Jun 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 8 Jun 2015). 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 Reactivity by VerifyNow P2Y12 (time frame: 1 hour). 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 NCT01898442, 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 8 Jun 2015; AzTrials last refreshed its copy on 27 Oct 2026.