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Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease (SWAP-2)

Primary Purpose

Coronary Artery Disease

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Prasugrel Loading Dose
Prasugrel Maintenance Dose
Ticagrelor Maintenance Dose
Sponsored by
Daiichi Sankyo, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring CAD, prasugrel, ticagrelor, antiplatelet, thienopyridine, P2Y12 Inhibitors

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Univ. of Florida College Medicine
  • Clinical Pharmacology Unit of Miami
  • Progressive Medical Research
  • Sinai Center for Thrombosis Research
  • Medpace Clinical Pharmacology Unit
  • Black Hills Cardiovascular Research
  • West Houston Area Clinical Trial Consultants
  • Cardiology Center of Houston
  • University Hospital of Wales
  • Bristol Heart Institute
  • University Hospital Leicester
  • Southampton General Hospital
  • New Cross Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Prasugrel Maintenance Dose

Ticagrelor Maintenance Dose

Prasugrel Loading Dose

Arm Description

Prasugrel 10 mg QD MD

Ticagrelor 90 mg twice-daily (BID) MD

Prasugrel 60mg Loading Dose (LD), followed by prasugrel 10mg once-daily (QD) Maintenance Dose (MD)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

P2Y12 Reaction Units
P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay measured at 2, 4, 24, 48 hours after first randomized study treatment
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.
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.
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.
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

Full Information

First Posted
April 26, 2012
Last Updated
December 19, 2018
Sponsor
Daiichi Sankyo, Inc.
Collaborators
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT01587651
Brief Title
Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease
Acronym
SWAP-2
Official Title
A Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease: 2nd Switching Antiplatelet Agents
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo, Inc.
Collaborators
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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)..

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
CAD, prasugrel, ticagrelor, antiplatelet, thienopyridine, P2Y12 Inhibitors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prasugrel Maintenance Dose
Arm Type
Experimental
Arm Description
Prasugrel 10 mg QD MD
Arm Title
Ticagrelor Maintenance Dose
Arm Type
Active Comparator
Arm Description
Ticagrelor 90 mg twice-daily (BID) MD
Arm Title
Prasugrel Loading Dose
Arm Type
Experimental
Arm Description
Prasugrel 60mg Loading Dose (LD), followed by prasugrel 10mg once-daily (QD) Maintenance Dose (MD)
Intervention Type
Drug
Intervention Name(s)
Prasugrel Loading Dose
Other Intervention Name(s)
Effient
Intervention Description
60mg given as six 10mg film coated tablets
Intervention Type
Drug
Intervention Name(s)
Prasugrel Maintenance Dose
Other Intervention Name(s)
Effient
Intervention Description
10mg maintenance dose, given as one 10mg film coated tablet
Intervention Type
Drug
Intervention Name(s)
Ticagrelor Maintenance Dose
Other Intervention Name(s)
Brilinta
Intervention Description
one 90mg film coated tablet
Primary Outcome Measure Information:
Title
P2Y12 Reaction Units
Description
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.
Time Frame
7 days after first randomized dose
Secondary Outcome Measure Information:
Title
P2Y12 Reaction Units
Description
P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay measured at 2, 4, 24, 48 hours after first randomized study treatment
Time Frame
2, 4, 24, 48 hours after first randomized dose
Title
Platelet Reactivity Index
Description
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.
Time Frame
2, 4, 24, 48 hours, 7 days after first randomized dose
Title
PRU Percent Inhibition (Device-reported)
Description
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.
Time Frame
2, 4, 24, 48 hours, 7 days after first randomized dose
Title
PRU Percent Inhibition (Calculated)
Description
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.
Time Frame
2, 4, 24, 48 hours, 7 days after first randomized dose
Title
Percentage of Subjects With High On-treatment Platelet Reactivity
Description
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
Time Frame
2, 4, 24, 48 hours, 7 days after first randomized dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Univ. of Florida College Medicine
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Clinical Pharmacology Unit of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
Progressive Medical Research
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
Sinai Center for Thrombosis Research
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
Medpace Clinical Pharmacology Unit
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45212
Country
United States
Facility Name
Black Hills Cardiovascular Research
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Facility Name
West Houston Area Clinical Trial Consultants
City
Houston
State/Province
Texas
ZIP/Postal Code
77094
Country
United States
Facility Name
Cardiology Center of Houston
City
Katy
State/Province
Texas
ZIP/Postal Code
77450
Country
United States
Facility Name
University Hospital of Wales
City
Heath Park
State/Province
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
Bristol Heart Institute
City
Bristol
ZIP/Postal Code
B52 8HW
Country
United Kingdom
Facility Name
University Hospital Leicester
City
Leicester
ZIP/Postal Code
LE3 9QP
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
New Cross Hospital
City
Wolverhampton
ZIP/Postal Code
WV10 0QP
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
IPD Sharing Time Frame
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
IPD Sharing Access Criteria
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/

Learn more about this trial

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

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