Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor

NCT02016170 | Completed Results DMC

• 1 other identifier: SWAP3
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease; Acute Coronary Syndrome

Keywords

platelet reactivity; ticagrelor; prasugrel

Outcome Measures

Primary Outcomes (1)

• Platelet Reactivity Measured as P2Y12 Reaction Units (PRU) Determined by Verify Now-P2Y12 Assay

  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 Outcomes (1)

• Platelet Reactivity Index (PRI) Measured by Whole Blood Vasodilator-stimulated Phosphoprotein (VASP).

  7 days

Study Arms (3)

Ticagrelor 180mg

EXPERIMENTAL

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

Drug: Ticagrelor 180mg

Ticagrelor 90mg

EXPERIMENTAL

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

Drug: Ticagrelor 90mg

Prasugrel 10mg

ACTIVE COMPARATOR

Patients already on prasugrel, will maintain prasugrel

Drug: Prasugrel 10mg

Interventions

Ticagrelor 180mg 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

Also known as: Brilinta

Ticagrelor 180mg

Prasugrel 10mg 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

Also known as: Effient

Prasugrel 10mg

Ticagrelor 90mg 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

Also known as: Brilinta

Ticagrelor 90mg

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (1)

• 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.

  PMID: 27013060 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Acute Coronary Syndrome

Interventions

Ticagrelor; Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dominick J. Angiolillo, MD, PhD
• Organization: University of Florida College of Medicine-Jacksonville

dominick.angiolillo@jax.ufl.edu

+1-904-244-3933

Study Officials

• Dominick Angiolillo, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2013
• First Posted: December 19, 2013
• Study Start: March 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: July 3, 2024
• Results First Posted: October 18, 2016

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)