Clinical trial NCT02016170: Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor
Official title: Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor: The SWAP (SWitching Anti Platelet)-3 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Acute Coronary Syndrome
Keywords: platelet reactivity
ticagrelor
prasugrel
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2013-12-19
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Recently, two new oral P2Y12 antagonists have been approved for clinical use: prasugrel, a third generation thienopyridine, and ticagrelor, a first in class cyclopentyltriazolopyrimidine (CPTP). These agents have been shown to be associated with more potent platelet inhibitory effects compared with clopidogrel. In addition, both agents have shown to be superior to clopidogrel in preventing recurrent ischemic events in the setting of acute coronary syndromes (ACS). Understanding how to switch patients from prasugrel to ticagrelor is an unmet need of clinical interest. The proposed PD investigation will have a prospective, randomized, parallel design aimed to show that switching patients from prasugrel to ticagrelor provides similar levels of platelet inhibition.

Detailed description: Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the cornerstone of treatment for secondary prevention of thrombotic events in patients with coronary artery disease. Recently, two new oral P2Y12 antagonists have been approved for clinical use: prasugrel, a third generation thienopyridine, and ticagrelor, a first in class cyclopentyltriazolopyrimidine (CPTP). These agents have been shown to be associated with more potent platelet inhibitory effects compared with clopidogrel. In addition, both agents have shown to be superior to clopidogrel in preventing recurrent ischemic events in the setting of acute coronary syndromes (ACS). Therefore, current guidelines recommend prasugrel or ticagrelor (as first line therapy according to European Society of Cardiology) in ACS patients undergoing percutaneous coronary intervention (PCI). Despite the broader indication for ticagrelor (also medically managed ACS) and its mortality benefit, prasugrel has a higher uptake than ticagrelor in the US market, likely due to its earlier approval. Further, implementation of prasugrel into institutional protocols, particularly for ST elevation myocardial infarction (STEMI) patients undergoing primary PCI, may also be a reason for the slow uptake of ticagrelor. However, many clinicians would indeed consider ticagrelor as the long-term treatment of choice for a variety of reasons. Therefore, understanding how to switch patients from prasugrel to ticagrelor is an unmet need of clinical interest. However, currently, there are no data on the pharmacodynamic (PD) effects of switching from prasugrel to ticagrelor. The proposed PD investigation will have a prospective, randomized, parallel design aimed to show that switching patients from prasugrel to ticagrelor provides similar levels of platelet inhibition. This study will provide insights on the PD effects of switching and will help clinicians to choose the most appropriate schema to avoid complications related to inadequate antiplatelet therapy in patients with coronary artery disease if switching from prasugrel to ticagrelor is desired.

Eligibility criteria: Inclusion Criteria:

* Patients with known coronary artery disease who presented with and ACS and underwent PCI.
* Age between 18 and 74 years old.
* On therapy with low-dose aspirin (81 mg) and prasugrel 10 mg/daily for at least 14 days as per standard of care

Exclusion criteria:

* History of stroke, transient ischemic attack (TIA) or intracranial bleeding.
* Known allergies to ticagrelor.
* Weight \< 60 Kg
* On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban).
* Treatment with IIb/IIIa glycoprotein inhibitors in the last 7 days.
* Blood dyscrasia or bleeding diathesis.
* Platelet count \<80x106/mL.
* Hemoglobin \<10 g/dL.
* Active bleeding.
* Hemodynamic instability.
* Creatinine Clearance \<30 mL/minute.
* Known severe hepatic dysfunction.
* Patients with sick sinus syndrome (SSS) or high degree atrio-ventricular block without pacemaker protection.
* Current treatment with drugs interfering with cytochrom P450 3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin.
* Pregnant females.

Primary outcomes:
measure: Platelet Reactivity Measured as P2Y12 Reaction Units (PRU) Determined by Verify Now-P2Y12 Assay
timeFrame: 7 days
Secondary outcomes:
measure: Platelet Reactivity Index (PRI) Measured by Whole Blood Vasodilator-stimulated Phosphoprotein (VASP).
timeFrame: 7 days
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Dominick Angiolillo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Franchi F, Faz GT, Rollini F, Park Y, Cho JR, Thano E, Hu J, Kureti M, Aggarwal N, Durairaj A, Been L, Zenni MM, Guzman LA, Suryadevara S, Antoun P, Bass TA, Angiolillo DJ. Pharmacodynamic Effects of Switching From Prasugrel to Ticagrelor: Results of the Prospective, Randomized SWAP-3 Study. JACC Cardiovasc Interv. 2016 Jun 13;9(11):1089-98. doi: 10.1016/j.jcin.2016.02.039. Epub 2016 Mar 21.