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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by LifeBridge Health
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
LifeBridge Health
ClinicalTrials.gov Identifier:
NCT01869309
First received: May 28, 2013
Last updated: November 20, 2014
Last verified: December 2013
  Purpose

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%.


Condition Intervention Phase
Coronary Artery Disease
Drug: Prasugrel
Drug: Ticagrelor
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Overcoming High On-Treatment Platelet Reactivity (HPR) During Prasugrel Therapy

Resource links provided by NLM:


Further study details as provided by LifeBridge Health:

Primary Outcome Measures:
  • Pharmacodynamic (PD) Vasodilator Stimulated Phosphoprotein-Phosphorylation(VASP-P) in High On Prasugrel Platelet Reactivity(HPPR) stable CAD patients [ Time Frame: 2 hours, 4 hours, and 14 days ] [ Designated as safety issue: No ]
    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:
  • Prevalence of HPPR [ Time Frame: 2 hours, 4 hours, and 14 days ] [ Designated as safety issue: No ]
    Determine the prevalence of HPPR in a stable PCI population.

  • CYP2C19 relation to occurence of HPPR [ Time Frame: 2 hours, 4 hours, and 14 days ] [ Designated as safety issue: No ]
    Determine the relation of CYP2C19 activity to the occurrence of HPPR.

  • PD VerifyNow in HPPR stable CAD patients [ Time Frame: 2 hour, 4 hour, 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 hours, 4 hours, 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 hours, 4 hours, and 14 days ] [ Designated as safety issue: No ]
    To determine the frequency of HPR after switching from ticagrelor to prasugrel after 14 days of treatment.

  • PD effect(Prasugrel) relation to CYP2C19 [ Time Frame: 2 hours, 4 hours, and 14 days ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: 14 days, 28 days ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of switching subjects from Prasugrel to Ticagrelor and vice versa.


Estimated Enrollment: 400
Study Start Date: January 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Non-HPR group
The non-HPR group will have PD and genetic testing, with no change in medication.
Active Comparator: HPR Group
This arm will be split into Group A and Group B which will receive Ticagrelor/Prasugrel in a crossover manner.
Drug: Prasugrel
Patients will discontinue ticagrelor treatment and start 10 mg prasugrel daily while continuing 81 mg of aspirin daily.
Drug: Ticagrelor
Patients will be given 180 mg of Ticagrelor followed by 90 mg twice a day while continuing 81 mg of aspirin daily).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01869309

Contacts
Contact: Kevin P Bliden, BS, MBA 4106014795 kbliden@lifebridgehealth.org

Locations
United States, Maryland
Sinai Center for Thrombosis Research Recruiting
Baltimore, Maryland, United States, 21215
Contact: Kevin P Bliden, B.S. MBA    410-601-4795    kbliden@lifebridgehealth.org   
Contact: Tania B Gesheff, MSN    4106014795    tgesheff@lifebridgehealth.org   
Sponsors and Collaborators
LifeBridge Health
AstraZeneca
Investigators
Principal Investigator: Paul A Gurbel, MD LifeBridge Health
  More Information

No publications provided

Responsible Party: LifeBridge Health
ClinicalTrials.gov Identifier: NCT01869309     History of Changes
Other Study ID Numbers: 2015, ISSBRIL0149
Study First Received: May 28, 2013
Last Updated: November 20, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by LifeBridge Health:
Coronary artery disease
anti-platelet medications
Platelet-aggregation Inhibitors

Additional relevant MeSH terms:
Platelet Aggregation Inhibitors
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Vascular Diseases
Prasugrel
Ticagrelor
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014