Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor

NCT ID: NCT02016170

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2015-10-31

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.

Conditions

Coronary Artery Disease; Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ticagrelor 180mg

Patients on prasugrel will switch to ticagrelor with a 180mg loading dose

Group Type: EXPERIMENTAL

Ticagrelor 180mg

Intervention Type: DRUG

After providing written informed consent, eligible patients on maintenance prasugrel meeting inclusion and exclusion criteria will be randomized in a 1:1:1 fashion to one of the following treatment arms:

A. Ticagrelor 180 mg loading dose (two 90mg ticagrelor tablets) followed by 90 mg BID maintenance dose for 7±2 days.

B. Ticagrelor 90 mg (one 90mg ticagrelor tablet) followed by 90 mg BID maintenance dose for 7±2 days C. Prasugrel 10 mg once daily maintenance dose for 7±2 days

Ticagrelor 90mg

Patients on prasugrel will switch to ticagrelor with a 90mg maintenance dose

Group Type: EXPERIMENTAL

Ticagrelor 90mg

Intervention Type: DRUG

After providing written informed consent, eligible patients on maintenance prasugrel therapy meeting inclusion and exclusion criteria will be randomized in a 1:1:1 fashion to one of the following treatment arms:

A. Ticagrelor 180 mg loading dose (two 90mg ticagrelor tablets) followed by 90 mg BID maintenance dose for 7±2 days.

B. Ticagrelor 90 mg (one 90mg ticagrelor tablet) followed by 90 mg BID maintenance dose for 7±2 days C. Prasugrel 10 mg once daily MD for 7±2 days

Prasugrel 10mg

Patients already on prasugrel, will maintain prasugrel

Group Type: ACTIVE_COMPARATOR

Prasugrel 10mg

Intervention Type: DRUG

After providing written informed consent, eligible patients on maintenance prasugrel therapy meeting inclusion and exclusion criteria will be randomized in a 1:1:1 fashion to one of the following treatment arms:

A. Ticagrelor 180 mg loading dose (two 90mg ticagrelor tablets) followed by 90 mg BID maintenance dose for 7±2 days.

B. Ticagrelor 90 mg (one 90mg ticagrelor tablet) followed by 90 mg BID maintenance dose for 7±2 days C. Prasugrel 10 mg once daily MD for 7±2 days

Interventions

Ticagrelor 180mg

After providing written informed consent, eligible patients on maintenance prasugrel meeting inclusion and exclusion criteria will be randomized in a 1:1:1 fashion to one of the following treatment arms:

A. Ticagrelor 180 mg loading dose (two 90mg ticagrelor tablets) followed by 90 mg BID maintenance dose for 7±2 days.

B. Ticagrelor 90 mg (one 90mg ticagrelor tablet) followed by 90 mg BID maintenance dose for 7±2 days C. Prasugrel 10 mg once daily maintenance dose for 7±2 days

Intervention Type: DRUG

Prasugrel 10mg

After providing written informed consent, eligible patients on maintenance prasugrel therapy meeting inclusion and exclusion criteria will be randomized in a 1:1:1 fashion to one of the following treatment arms:

A. Ticagrelor 180 mg loading dose (two 90mg ticagrelor tablets) followed by 90 mg BID maintenance dose for 7±2 days.

B. Ticagrelor 90 mg (one 90mg ticagrelor tablet) followed by 90 mg BID maintenance dose for 7±2 days C. Prasugrel 10 mg once daily MD for 7±2 days

Intervention Type: DRUG

Ticagrelor 90mg

After providing written informed consent, eligible patients on maintenance prasugrel therapy meeting inclusion and exclusion criteria will be randomized in a 1:1:1 fashion to one of the following treatment arms:

A. Ticagrelor 180 mg loading dose (two 90mg ticagrelor tablets) followed by 90 mg BID maintenance dose for 7±2 days.

B. Ticagrelor 90 mg (one 90mg ticagrelor tablet) followed by 90 mg BID maintenance dose for 7±2 days C. Prasugrel 10 mg once daily MD for 7±2 days

Intervention Type: DRUG

Other Intervention Names

Brilinta; Effient; Brilinta

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominick Angiolillo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Jacksonville, Florida, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27013060 (View on PubMed)

Other Identifiers

SWAP3

Identifier Type: -

Identifier Source: org_study_id