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

LifeBridge Health

Status and phase: Unknown; Phase 4

Conditions: Coronary Artery Disease

Treatments: Drug: Prasugrel; Drug: Ticagrelor

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01869309

2015

ISSBRIL0149 (Other Identifier)

Details and patient eligibility

About

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%.

Enrollment: 400 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Non-HPR group

No Intervention group

Description:

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

HPR Group

Active Comparator group

Description:

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

Treatment:

Drug: Prasugrel

Drug: Ticagrelor