Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease

Coronary Artery Disease Clinical Trial

— SWAP-2  

Official title:

A Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease: 2nd Switching Antiplatelet Agents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01587651
• Other study ID #: CS747s-B-U4003
• Status: Completed
• Phase: Phase 4
• Start date: March 2012
• Est. completion date: February 2013

Study information

• Verified date: March 2014
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 4, multicenter, open-label (blinded Pharmacodynamic PD results), randomized, 3-arm, parallel-design study of subjects with stable Coronary Artery Disease CAD. This study will compare the PD effect of prasugrel 10 mg QD (once-daily) maintenance dose with ticagrelor 90 mg BID (twice daily) maintenance dose in subjects with stable CAD who have previously received ticagrelor loading does (LD) and maintenance dose (MD)..

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• Male or female; age >= 18 and < 75 years

• Weight >= 60 kg

• Receiving low dose ASA (75 mg to 150 mg daily) for at least 7 days at the time of Visit 1 and able to continue the same regimen throughout the study

• Stable CAD. CAD is defined as any of the following:

• History of a positive stress test

• Previous coronary revascularization including percutaneous coronary intervention (PCI), stent, or coronary artery bypass graft (CABG)

• Angiographic demonstration of CAD (at least

1 lesion >= 50 percent)

• Presence of at least moderate plaque by computed tomography (CT) angiography

• Electron beam CT coronary artery calcification score >= 100 Agatston units

• If female, may be enrolled if

One of the following 3 criteria are met:

• Had a hysterectomy or tubal ligation at least 6 months prior to signing the informed consent form (ICF)

• Post-menopausal for at least 1 year

• If of childbearing potential, will practice 1 of the following methods of birth control throughout the study: oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide; or female condom plus spermicide. Methods of contraception that are not acceptable are partner's use of condoms or partner's vasectomy

• Able and willing to provide written informed consent before entering the study

Exclusion Criteria:

• Have a defined need for adenosine diphosphate (ADP)-receptor inhibitor therapy, such as any of the following (or any other condition that in the Investigator's judgment would require such therapy):

• Within =< 12 months of an acute coronary syndrome (ACS) event (unstable angina [UA], non-ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]) regardless of initial treatment (that is, invasive versus noninvasive)

• Subjects who underwent angioplasty within 12 months including bare-metal stent and/or a drug-eluting stent

• Had any stent placed in an unprotected left main coronary artery or in the last patent artery within the last 12 months

• Received thienopyridine therapy within 30 days of study entry

• Plan to undergo coronary revascularization at any time during the trial

• Presence or history of any of the following: ischemic or hemorrhagic stroke; transient ischemic attack (TIA); intracranial neoplasm; arteriovenous malformation, or aneurysm; intracranial hemorrhage; head trauma (within 3 months of study entry)

• History of refractory ventricular arrhythmias with an increased risk of bradycardic events (eg, subjects without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block or bradycardic-related syncope)

• History or evidence of congestive heart failure (New York Heart Association Class III or above =< 6 months before screening

• Severe hepatic impairment

• History of uric acid nephropathy

• Uncontrolled hypertension, or systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg at screening

• Severely impaired renal function (glomerular filtration rate < 30 mL/minute) or on dialysis

• At risk for bleeding

• Taking prohibited medications

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Prasugrel Loading Dose
60mg given as six 10mg film coated tablets
• Prasugrel Maintenance Dose
10mg maintenance dose, given as one 10mg film coated tablet
• Ticagrelor Maintenance Dose
one 90mg film coated tablet

Locations

Country	Name	City	State
United Kingdom	Bristol Heart Institute	Bristol
United Kingdom	University Hospital of Wales	Heath Park	Cardiff
United Kingdom	University Hospital Leicester	Leicester
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	New Cross Hospital	Wolverhampton
United States	Sinai Center for Thrombosis Research	Baltimore	Maryland
United States	Medpace Clinical Pharmacology Unit	Cincinnati	Ohio
United States	West Houston Area Clinical Trial Consultants	Houston	Texas
United States	Univ. of Florida College Medicine	Jacksonville	Florida
United States	Cardiology Center of Houston	Katy	Texas
United States	Clinical Pharmacology Unit of Miami	Miami	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	Black Hills Cardiovascular Research	Rapid City	South Dakota

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	P2Y12 Reaction Units	P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay VerifyNow P2Y12 assay, developed by Accumetrics, Inc. (San Diego, CA, USA), has been approved by the FDA to assess clopidogrel response using whole blood in a point-of-care testing fashion. Platelet aggregation with this system is defined by PRU, with a higher PRU indicative of greater platelet aggregation, and a lower PRU indicative of inhibition.	7 days after first randomized dose
Secondary	P2Y12 Reaction Units	P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay measured at 2, 4, 24, 48 hours after first randomized study treatment	2, 4, 24, 48 hours after first randomized dose
Secondary	Platelet Reactivity Index	Platelet Reactivity Index (PRI) by the Vasodilator-Stimulated Phosphoprotein(VASP) assay 2, 4, 24, 48 hours and 7 days after first randomized study treatment.; The VASP assay is an indirect, but relatively specific measure of inhibition of P2Y12-induced platelet activation. The assay quantifies the level of phosphorylation of the intracellular protein VASP, which undergoes phosphorylation when platelet P2Y12 receptors are blocked. The level of VASP phosphorylation, expressed as the PRI, represents the percentage inhibition relative to an assay baseline/maximal P2Y12-independent platelet aggregation.	2, 4, 24, 48 hours, 7 days after first randomized dose
Secondary	PRU Percent Inhibition (Device-reported)	PRU VerifyNow P2Y12 assay device-reported percent inhibition 2, 4, 24, and 48 hours, and 7 days after first randomized study treatment; VerifyNow P2Y12 assay, developed by Accumetrics, Inc. (San Diego, CA, USA), has been approved by the FDA to assess clopidogrel response using whole blood in a point-of-care testing fashion. The percent inhibition reported by VerifyNow device represents the percentage inhibition relative to maximal P2Y12-independent platelet aggregation achieved with the same sample in the presence of the iso-thrombin receptor activating peptide.	2, 4, 24, 48 hours, 7 days after first randomized dose
Secondary	PRU Percent Inhibition (Calculated)	Analysis of Mean Calculated Percent Inhibition by time point; Calculated percent inhibition at time point t is defined as: 100 × (baseline PRU - PRUt)/baseline PRU where baseline PRU is the VerifyNow PRU value at pre-run-in baseline and PRUt is the VerifyNow PRU value at time t.	2, 4, 24, 48 hours, 7 days after first randomized dose
Secondary	Percentage of Subjects With High On-treatment Platelet Reactivity	Percentage of subjects with High on-treatment Platelet Reactivity (HPR) defined as a) >= 208 PRU and b) >= 230 PRU by the VerifyNow P2Y12 assay and c) >50% PRI by the VASP assay, 2, 4, 24, and 48 hours and 7 days after first randomized study treatment.; A poor response of the platelets to "drug", called High Residual Platelet Reactivity (HRPR), has been incriminated to account for a recurrence of ischemic events	2, 4, 24, 48 hours, 7 days after first randomized dose