Ticagrelor vs Clopidogrel Effect on MFR in CAD Population (PATH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Ottawa Heart Institute Research Corporation
Sponsor:
Information provided by (Responsible Party):
Terrence Ruddy, Ottawa Heart Institute Research Corporation
ClinicalTrials.gov Identifier:
NCT01894789
First received: February 27, 2013
Last updated: October 7, 2014
Last verified: October 2014
  Purpose

Ticagrelor is one of 3 anti-platelet medications used in patients with acute coronary syndrome (ACS) to prevent further clot formation and further ischemic damage to myocardial tissue. Overall benefits of one drug over the other is neutral in this generally unstable population. In pre-clinical trials, ticagrelor showed secondary effects, involving the release of adenosine to heart muscle where the demand for blood was increased due to a stress condition. Blood flow was increased, potentially preventing potential damage.

This study will compare ticagrelor, currently only approved for use in ACS patients, against clopidogrel by measuring the myocardial blood flow(MBF) during stress to validate this phenomenon. The effect on blood flow will be measurable by using two specific doses of adenosine as the pharmacologic stress and correlating with measurements of blood flow using positron emission tomography (PET) nuclear imaging.

This study hypothesizes that the increase in MBF during intermediate dose adenosine infusion will be greater in ticagrelor treated subjects compared to clopidogrel treated subjects


Condition Intervention Phase
Coronary Artery Disease
Drug: Ticagrelor
Drug: Clopidogrel
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ComPArison of the Effect of Ticagrelor Versus Clopidogrel on Myocardial Blood Flow (MBF) and Reserve (MBFR) Measured With Positron Emission TomograpHy (PET) in Patients With Coronary Artery Disease (CAD): The PATH Study

Resource links provided by NLM:


Further study details as provided by Ottawa Heart Institute Research Corporation:

Primary Outcome Measures:
  • Differences in rest MBF, stress MBF and MBFR between ticagrelor and clopidogrel treated patients as measured by PET [ Time Frame: q 2 weeks blood flow measurements ] [ Designated as safety issue: No ]

    Blinded study drug will be administered for 10 days after which the subject will undergo MPI imaging to measure MBF. The crossover to the other study arm will occur and the study procedure repeated.

    Actual study drug effect will not be known until the study has completed and the treatment unblinded.



Secondary Outcome Measures:
  • The effect of ticagrelor on rest MBF, stress MBF and MBFR will be compared in the normal versus abnormal segments on a segmental and patient basis in the ticagrelor treated subjects [ Time Frame: q 2 weeks blood flow measurements ] [ Designated as safety issue: No ]

    Blinded study drug will be administered for 10 days after which the subject will undergo MPI imaging to measure rest/stress MBF and myocardial blood flow reserve. The crossover to the other study arm will occur and the study procedure repeated.

    Actual study drug effecting flow will not be known until the study has completed and the treatment unblinded.



Estimated Enrollment: 36
Study Start Date: March 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: stable CAD management
Experimental: Ticagrelor (BrilintaTM) 90 mg tablet by mouth twice a day
Drug: Ticagrelor
Blinded administration of ticagrelor for 10 days
Other Name: BrilintaTM
Drug: Clopidogrel
Blinded administration of clopidogrel and placebo for 10 days
Active Comparator: CAD comparison group
Active comparator: clopidogrel 75 mg plus placebo tablet by mouth twice a day.
Drug: Ticagrelor
Blinded administration of ticagrelor for 10 days
Other Name: BrilintaTM
Drug: Clopidogrel
Blinded administration of clopidogrel and placebo for 10 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years old
  2. Stable coronary artery disease on stable medical treatment.
  3. BMI equal to or less than 30 kg/m2
  4. No clinically significant abnormalities in baseline laboratory work
  5. No clinically significant arrhythmias on baseline 12-lead electrocardiogram
  6. Female subjects must be post-menopausal, surgically sterilized or have negative urine beta human chorionic gonadotropin pregnancy test at initial screening and maintain effective contraceptive methods throughout the trial and for 7 days following the end of dosing treatment.

Exclusion Criteria:

  1. Any contraindication against the use of clopidogrel, ticagrelor and/or ASA.
  2. Oral anticoagulation therapy.
  3. History of intracranial bleeding.
  4. Recent or active pathological bleeding, such as peptic ulcer.
  5. Moderate or severe hepatic impairment.
  6. History or risk of bradycardia.
  7. Known second- or third-degree AV block without pacemaker
  8. Dyspnea (NYHA III/IV), wheezing asthma or COPD.
  9. Coronary artery bypass graft (CABG) surgery within 90 days prior to screening or at any time after consent.
  10. Percutaneous coronary intervention (PCI) within 90 days prior to screening or at any time following consent.
  11. Acute myocardial infarction or acute coronary syndrome within 60 days prior to screening or at any time following consent.
  12. Any scheduled surgery during the trial period, including dental.
  13. Concomitant therapy with strong cytochrome CYP 3A inhibitor or inducer.
  14. Recent use of dipyridamole, dipyridamole-containing medications (e.g. Aggrenox)
  15. Known hypersensitivity to the investigational drug or any of its components.
  16. Known hypersensitivity to adenosine.
  17. Lactose intolerance
  18. Breastfeeding or pregnancy.
  19. Claustrophobia or inability to lie still in a supine position
  20. Unwillingness to provide informed consent
  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: NCT01894789

Contacts
Contact: Marlie Poirier, BScN 613-761-5103 mpoirier@ottawaheart.ca
Contact: Brian Marvin, NMT 614-798-5555 ext 13281 bmarvin@ottawaheart.ca

Locations
Canada, Ontario
University of Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Contact: Marlie Poirier, BScN    613-761-5103    mpoirier@ottawaheart.ca   
Principal Investigator: Terrence Ruddy, MD         
Sponsors and Collaborators
Ottawa Heart Institute Research Corporation
Investigators
Principal Investigator: Terrence Ruddy, MD Ottawa Heart Institute Research Corporation
  More Information

No publications provided

Responsible Party: Terrence Ruddy, Dr. Terrence Ruddy, Ottawa Heart Institute Research Corporation
ClinicalTrials.gov Identifier: NCT01894789     History of Changes
Other Study ID Numbers: 20130105-01H
Study First Received: February 27, 2013
Last Updated: October 7, 2014
Health Authority: Canada: Health Canada

Keywords provided by Ottawa Heart Institute Research Corporation:
myocardial blood flow
myocardial perfusion imaging
myocardial blood flow reserve
positron emission tomography
adenosine
ticagrelor
clopidogrel

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

ClinicalTrials.gov processed this record on October 22, 2014