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

Coronary Artery Disease Clinical Trial

— HEIGHTEN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01869309
• Other study ID #: 2015
• Secondary ID: ISSBRIL0149
• Status: Recruiting
• Phase: Phase 4
• First received: May 28, 2013
• Last updated: November 20, 2014
• Start date: January 2014
• Est. completion date: December 2016

Study information

• Verified date: December 2013
• Source: LifeBridge Health
• Contact: Kevin P Bliden, BS, MBA
• Phone: 4106014795
• Email: kbliden[@]lifebridgehealth.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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%.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Prasugrel
Patients will discontinue ticagrelor treatment and start 10 mg prasugrel daily while continuing 81 mg of aspirin daily.
• Ticagrelor
Patients will be given 180 mg of Ticagrelor followed by 90 mg twice a day while continuing 81 mg of aspirin daily).

Locations

Country	Name	City	State
United States	Sinai Center for Thrombosis Research	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
LifeBridge Health	AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants with Adverse Events	To evaluate the safety and tolerability of switching subjects from Prasugrel to Ticagrelor and vice versa.	14 days, 28 days	Yes
Primary	Pharmacodynamic (PD) Vasodilator Stimulated Phosphoprotein-Phosphorylation(VASP-P) in High On Prasugrel Platelet Reactivity(HPPR) stable CAD patients	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%.	2 hours, 4 hours, and 14 days	No
Secondary	Prevalence of HPPR	Determine the prevalence of HPPR in a stable PCI population.	2 hours, 4 hours, and 14 days	No
Secondary	CYP2C19 relation to occurence of HPPR	Determine the relation of CYP2C19 activity to the occurrence of HPPR.	2 hours, 4 hours, and 14 days	No
Secondary	PD VerifyNow in HPPR stable CAD patients	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	2 hour, 4 hour, 14 days	No
Secondary	PD LTA in HPPR stable CAD patients	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)	2 hours, 4 hours, 14 days	No
Secondary	Frequency of HPR	To determine the frequency of HPR after switching from ticagrelor to prasugrel after 14 days of treatment.	2 hours, 4 hours, and 14 days	No
Secondary	PD effect(Prasugrel) relation to CYP2C19	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.	2 hours, 4 hours, and 14 days	No