Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor (SWAP3)

August 22, 2016 updated by: Dominick Angiolillo, University of Florida

Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor: The SWAP (SWitching Anti Platelet)-3 Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 74 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ticagrelor 180mg
Patients on prasugrel will switch to ticagrelor with a 180mg loading dose
Drug: 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

Other Names:
  • Brilinta
EXPERIMENTAL: Ticagrelor 90mg
Patients on prasugrel will switch to ticagrelor with a 90mg maintenance dose
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

Other Names:
  • Brilinta
ACTIVE_COMPARATOR: Prasugrel 10mg
Patients already on prasugrel, will maintain prasugrel
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

Other Names:
  • Effient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet Reactivity Measured as P2Y12 Reaction Units (PRU) Determined by Verify Now-P2Y12 Assay
Time Frame: 7 days
The primary hypothesis of our study was that after 1 week of randomized treatment PRU levels would be non-inferior in patients switched from prasugrel to ticagrelor (two arms combined) compared with patients remaining on prasugrel.
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet Reactivity Index (PRI) Measured by Whole Blood Vasodilator-stimulated Phosphoprotein (VASP).
Time Frame: 7 days
The secondary hypothesis of our study was that after 1 week of randomized treatment PRI levels would be non-inferior in patients switched from prasugrel to ticagrelor (two arms combined) compared with patients remaining on prasugrel. VASP was measured by quantitative flow cytometry using commercially available labelled monoclonal antibodies.
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (ACTUAL)

October 1, 2015

Study Completion (ACTUAL)

October 1, 2015

Study Registration Dates

First Submitted

December 13, 2013

First Submitted That Met QC Criteria

December 13, 2013

First Posted (ESTIMATE)

December 19, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

October 18, 2016

Last Update Submitted That Met QC Criteria

August 22, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SWAP3

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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