- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02943369
Cangrelor Following Ticagrelor Loading vs Ticagrelor Loading Alone in STEMI
Cangrelor Administration Following Ticagrelor Loading vs Ticagrelor Loading Alone in ST Segment Elevation Myocardial Infarction Patients: A Randomized, Pharmacodynamic Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
A rapid and consistent platelet inhibition represents the cornerstone of pharmacological treatment in the early hours of ST-segment elevation myocardial infarction (STEMI) with expected improvement in outcome. Current practice guidelines recommend administration of a loading dose (LD) of an oral P2Y12 receptor antagonist as early as possible or at the time of percutaneous coronary intervention (PCI) or at first medical contact.
Pharmacodynamic data have clearly shown a delay in the onset of action when prasugrel or ticagrelor are administered in patients with STEMI - compared to what is obtained in stable or acute coronary syndrome (ACS) patients-, which is most likely caused by an impaired absorption. Peri-interventional platelet inhibition is therefore suboptimal in most cases of timely performed primary PCI, even when novel oral antiplatelet agents with faster than clopidogrel action are used. Modifications of the loading dose or antiplatelet pre-hospital administration may only partially 'bridge the gap" in platelet inhibition.
On the other hand, cangrelor is a parenteral P2Y12 antagonist, with a rapid -within minutes- onset of action, able to provide very strong and consistent platelet inhibition and with rapid offset of action- within 60 min of infusion discontinuation. In the CHAMPION PHOENIX (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trial cangrelor reduced the incidence of ischemic events, without increasing the incidence of severe bleeding. Ticagrelor is an oral antiplatelet agent which has been reported that can be given before or during infusion of cangrelor without attenuation of cangrelor's pharmacodynamic effects, while the pharmacodynamic effects of ticagrelor are preserved when ticagrelor is given during infusion of cangrelor. It seems therefore, that ticagrelor has favorable characteristics for patients intended to receive cangrelor.
In the present study, in STEMI patients undergoing primary PCI the investigators aim to compare platelet inhibition achieved in patients loaded with ticagrelor followed by cangrelor (bolus plus infusion) vs ticagrelor alone loaded patients.
This will be a prospective, randomized, 3-center, single-blind, investigator-initiated study of parallel design to compare platelet inhibition provided by ticagrelor LD plus cangrelor (bolus and infusion) vs ticagrelor LD alone. Participants will be consecutive P2Y12 inhibitor-naive STEMI patients with pain onset<12 hours admitted for primary PCI will be considered.
Participants in both arms will receive ticagrelor 180 mg LD as early as possible (e.g. in the spoke hospital in case of transfer or at the emergency department in cases of hub hospital presentation), as per local practice. The exact time of ticagrelor administration will be recorded. Randomization followed by immediate initiation of cangrelor administration will be performed after angiography and immediately prior to PCI. Patients will be randomized (Hour 0) in a 1:1 ratio by an independent investigator to cangrelor 30 mcg/kg bolus + 4 mcg/kg/min for 2 hours, or no IV antiplatelet .
Other treatment will be as per local standard of care in all participants. Investigators who will perform platelet function testing will be blind to the actual treatment assignment, whereas an independent investigator will monitor bleeding and adverse event data.
Platelet reactivity will be measured at randomization (Hour 0) and at 15 min, 1, 2 and 4 hours post randomization. Platelet function testing will be performed with the VerifyNow (Accumetrics Inc, San Diego, CA) point-of-care P2Y12 function assay within 30 min from blood sample collection. Platelet reactivity results will be reported in P2Y12 reaction units (PRU) and % inhibition. The % inhibition is calculated as: ([BASE-PRU]/BASE)×100. High platelet reactivity (HPR) will be defined as ≥208 PRU.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Attika
-
Athens, Attika, Greece, 12462
- Attikon University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Consecutive P2Y12 inhibitor-naive STEMI patients with pain onset<12 hours admitted for primary PCI.
Exclusion Criteria:
- a history of stroke/transient ischemic attack
- bleeding diathesis
- chronic oral anticoagulation treatment
- contraindications to anti platelet therapy
- PCI or coronary artery bypass grafting <3 months
- platelet count <100 000/μL
- hematocrit <30%
- creatinine clearance <30 mL/min
- severe hepatic dysfunction
- use of strong CYP3A inhibitors or inducers
- increased risk of bradycardia
- severe chronic obstructive pulmonary disease
- periprocedural IIb/IIIa inhibitor administration.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cangrelor
Ticagrelor will be followed by Cangrelor
|
Ticagrelor 180 mg
Other Names:
Intravenous Cangrelor 30 mcg/kg bolus + 4 mcg/kg/min for 2 hours
Other Names:
|
Active Comparator: Ticagrelor
Ticagrelor only
|
Ticagrelor 180 mg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Platelet reactivity between the 2 arms
Time Frame: 15 min
|
Platelet reactivity in P2Y12 reaction units by VerifyNow assay
|
15 min
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Platelet reactivity between the 2 arms
Time Frame: 1 hour
|
Platelet reactivity in P2Y12 reaction units by VerifyNow assay
|
1 hour
|
Platelet reactivity between the 2 arms
Time Frame: 2 hours
|
Platelet reactivity in P2Y12 reaction units by VerifyNow assay
|
2 hours
|
Platelet reactivity between the 2 arms
Time Frame: 4 hours
|
Platelet reactivity in P2Y12 reaction units by VerifyNow assay
|
4 hours
|
High on treatment platelet reactivity rate
Time Frame: 15 min
|
High on treatment platelet reactivity rate
|
15 min
|
High on treatment platelet reactivity rate
Time Frame: 1 hour
|
High on treatment platelet reactivity rate
|
1 hour
|
High on treatment platelet reactivity rate
Time Frame: 2 hours
|
High on treatment platelet reactivity rate
|
2 hours
|
High on treatment platelet reactivity rate
Time Frame: 4 hours
|
High on treatment platelet reactivity rate
|
4 hours
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
major adverse cardiac events (death, myocardial infarction, stroke, ischemia driven revascularization)
Time Frame: 30 days
|
30 days
|
Bleeding events (BARC classification)
Time Frame: 30 days
|
30 days
|
Other adverse events
Time Frame: 30 days
|
30 days
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Ischemia
- Pathologic Processes
- Necrosis
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Myocardial Infarction
- Infarction
- ST Elevation Myocardial Infarction
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Platelet Aggregation Inhibitors
- Purinergic P2Y Receptor Antagonists
- Purinergic P2 Receptor Antagonists
- Purinergic Antagonists
- Purinergic Agents
- Ticagrelor
- Cangrelor
Other Study ID Numbers
- IIS13616
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on STEMI
-
Clinical Operations WCN B.V.SanofiEnrolling by invitationAtherosclerotic Cardiovascular Disease | STEMI | Non STEMINetherlands
-
Kingston UniversityUniversity of Leeds; Swansea University; London Ambulance Service; West Midlands... and other collaboratorsCompletedAcute Coronary Syndrome | STEMI | Non STEMIUnited Kingdom
-
Karolinska InstitutetEnrolling by invitation
-
Beijing Friendship HospitalActive, not recruiting
-
University of OradeaCompleted
-
Prolocor, IncRecruitingSTEMI | NSTEMIUnited States
-
Assistance Publique - Hôpitaux de ParisCompletedPrimary PCI - STEMIFrance
-
VesalioRecruitingSegment Elevation Myocardial Infarction (STEMI)Switzerland
-
University of PisaCompleted
-
AstraZenecaCompletedMyocardial Infarction | Segment Elevation Myocardial Infarction (STEMI)Australia, France, Italy, Spain, United Kingdom, Sweden, Germany, Hungary, Denmark, Austria, Canada, Netherlands, Algeria
Clinical Trials on Ticagrelor 180 mg loading dose
-
BiocadCompleted
-
Dong-A UniversityTerminatedST-Segment Elevation Myocardial InfarctionKorea, Republic of
-
University of PatrasCompletedST Elevation Myocardial Infarction | Fibrinolysis | P2Y12 InhibitorGreece
-
Grace Lim, MD, MSNational Institute of Mental Health (NIMH)RecruitingPain, Postoperative | Depression, PostpartumUnited States
-
Daiichi Sankyo, Inc.Eli Lilly and CompanyCompletedCoronary Artery DiseaseUnited Kingdom, United States
-
Icahn School of Medicine at Mount SinaiAstraZenecaCompleted
-
University Magna GraeciaCompletedAcute Coronary SyndromeItaly
-
AstraZenecaCompletedHealthy Subjects | BioavailabilityGermany
-
Germano Di SciascioCardiovascular Center Aalst, OLV Clinic, Aalst, Belgium; Department of Advanced... and other collaboratorsCompleted