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

NCT01869309 | Unknown Phase 4

• 2 other identifiers: 2015ISSBRIL0149
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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%.

Conditions

Coronary Artery Disease

Keywords

Coronary artery disease; anti-platelet medications; Platelet-aggregation Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Prevalence of HPPR

  2 hours, 4 hours, and 14 days

• CYP2C19 relation to occurence of HPPR

  2 hours, 4 hours, and 14 days

• PD VerifyNow in HPPR stable CAD patients

  2 hour, 4 hour, 14 days

• PD LTA in HPPR stable CAD patients

  2 hours, 4 hours, 14 days

• Frequency of HPR

  2 hours, 4 hours, and 14 days

Other Outcomes (1)

• Number of Participants with Adverse Events

  14 days, 28 days

Study Arms (2)

Non-HPR group

NO INTERVENTION

The non-HPR group will have PD and genetic testing, with no change in medication.

HPR Group

ACTIVE COMPARATOR

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

Drug: Prasugrel; Drug: Ticagrelor

Interventions

Prasugrel DRUG

Patients will discontinue ticagrelor treatment and start 10 mg prasugrel daily while continuing 81 mg of aspirin daily.

HPR Group

Ticagrelor DRUG

Patients will be given 180 mg of Ticagrelor followed by 90 mg twice a day while continuing 81 mg of aspirin daily).

HPR Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female; age ≥ 18 and \< 75 years
• Weight ≥ 60 kg
• Currently on ASA therapy and eligible to reduce ASA dose to 81 mg daily if on higher dosing
• On stable prasugrel maintenance dose for ≥1 month
• 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.
• 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.
• Able and willing to provide written informed consent before entering the study

You may not qualify if:

• Subject plans 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 defined as ALT\> 2.5 X ULN
• 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
• Concomitant use with parenteral or oral anticoagulants
• Platelet count \<100 X103

Sponsors & Collaborators

• LifeBridge Health: lead
• AstraZeneca: collaborator

Study Sites (1)

Sinai Center for Thrombosis Research

Baltimore, Maryland, 21215, United States

RECRUITING

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Prasugrel Hydrochloride; Ticagrelor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Paul A Gurbel, MD

  LifeBridge Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin P Bliden, BS, MBA

CONTACT

4106014795; kbliden@lifebridgehealth.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2013
• First Posted: June 5, 2013
• Study Start: January 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: November 21, 2014

Record last verified: 2013-12

Locations

US (1)