Overcoming High On-Treatment Platelet Reactivity (HPR) During Prasugrel Therapy With Ticagrelor

Phase 4

• Conditions: Coronary Artery Disease
• Interventions: Drug: Prasugrel; Drug: Ticagrelor

• Registration Number: NCT01869309
• Lead Sponsor: LifeBridge Health

Brief Summary

The primary objective is to determine the pharmacodynamic effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable Coronary artery disease (CAD) patients who exhibit high-on prasugrel platelet reactivity defined as Vasodilator Stimulated Phosphoprotein-Phosphorylation (VASP-P) \>50%.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-05-28
• Study First Submitted QC: 2013-05-30
• Study First Posted: 2013-06-05
• Status Verified: 2013-12
• Study Start: 2014-01
• Last Update Submitted: 2014-11-20
• Last Update Posted: 2014-11-21
• Primary Completion: 2015-12
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Male or female; age ≥ 18 and < 75 years
2. Weight ≥ 60 kg
3. Currently on ASA therapy and eligible to reduce ASA dose to 81 mg daily if on higher dosing
4. On stable prasugrel maintenance dose for ≥1 month
5. Stable CAD patients defined as: subjects with documented evidence of a history of atherosclerotic coronary artery disease/surgical revascularization (defined as either a prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft surgery). A minimum of 1 month must have elapsed between a subject's enrolment and any acute event, revascularization procedure or hospitalization for chest pain for that subject.
6. If female, may be enrolled if one of the following 3 criteria are met: 1)Had a hysterectomy or tubal ligation at least 6 months prior to signing ICF, 2)Post-menopausal for at least 1 year, 3)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.
7. Able and willing to provide written informed consent before entering the study

Exclusion Criteria

1. Subject plans to undergo coronary revascularization at any time during the trial
2. 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)
3. 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)
4. History or evidence of congestive heart failure (New York Heart Association Class III or above ≤ 6 months before screening
5. Severe hepatic impairment defined as ALT> 2.5 X ULN
6. Uncontrolled hypertension, or systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg at screening
7. Severely impaired renal function (glomerular filtration rate < 30 mL/minute) or on dialysis
8. Concomitant use with parenteral or oral anticoagulants
9. Platelet count <100 X103

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
HPR Group	Prasugrel	This arm will be split into Group A and Group B which will receive Ticagrelor/Prasugrel in a crossover manner.
HPR Group	Ticagrelor	This arm will be split into Group A and Group B which will receive Ticagrelor/Prasugrel in a crossover manner.

Primary Outcome Measures

Name	Time	Method
Pharmacodynamic (PD) Vasodilator Stimulated Phosphoprotein-Phosphorylation(VASP-P) in High On Prasugrel Platelet Reactivity(HPPR) stable CAD patients	2 hours, 4 hours, and 14 days	The primary objective is to determine the pharmacodynamic effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable CAD patients who exhibit high-on prasugrel platelet reactivity defined as VASP-P\>50%.

Secondary Outcome Measures

Name	Time	Method
PD VerifyNow in HPPR stable CAD patients	2 hour, 4 hour, 14 days	Evaluate the PD effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable CAD patients who exhibit HPPR defined as PRU \>208 by VerifyNow P2Y12
PD LTA in HPPR stable CAD patients	2 hours, 4 hours, 14 days	Evaluate the PD effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable CAD patients who exhibit HPPR based on light transmittance aggregometry (5 and 20 uM ADP, 4ug/mL Collagen)
Frequency of HPR	2 hours, 4 hours, and 14 days	To determine the frequency of HPR after switching from ticagrelor to prasugrel after 14 days of treatment.
Prevalence of HPPR	2 hours, 4 hours, and 14 days	Determine the prevalence of HPPR in a stable PCI population.
CYP2C19 relation to occurence of HPPR	2 hours, 4 hours, and 14 days	Determine the relation of CYP2C19 activity to the occurrence of HPPR.
PD effect(Prasugrel) relation to CYP2C19	2 hours, 4 hours, and 14 days	To determine if the PD effect of prasugrel is related to the activity of CYP2C19 (phenotyping and genotyping) by measuring patients with and without HPPR.

Trial Locations

Locations (1)

Sinai Center for Thrombosis Research; 🇺🇸 Baltimore, Maryland, United States