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Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor (SWAP3)

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ClinicalTrials.gov Identifier: NCT02016170
Recruitment Status : Completed
First Posted : December 19, 2013
Results First Posted : October 18, 2016
Last Update Posted : October 18, 2016
Sponsor:
Information provided by (Responsible Party):
Dominick Angiolillo, University of Florida

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.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Acute Coronary Syndrome Drug: Ticagrelor 180mg Drug: Prasugrel 10mg Drug: Ticagrelor 90mg Not Applicable

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  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor: The SWAP (SWitching Anti Platelet)-3 Study
Study Start Date : March 2014
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: Effient




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02016170


Locations
United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Dominick Angiolillo, MD, PhD University of Florida

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dominick Angiolillo, Associate Professor of Medicine, University of Florida
ClinicalTrials.gov Identifier: NCT02016170     History of Changes
Other Study ID Numbers: SWAP3
First Posted: December 19, 2013    Key Record Dates
Results First Posted: October 18, 2016
Last Update Posted: October 18, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Dominick Angiolillo, University of Florida:
platelet reactivity
ticagrelor
prasugrel

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Acute Coronary Syndrome
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
Adenosine
Prasugrel Hydrochloride
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists