Ticagrelor vs Clopidogrel Effect on MFR in CAD Population

NCT01894789 | Completed Phase 2 DMC

• 1 other identifier: 20130105-01H
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Coronary Artery Disease

Keywords

myocardial blood flow; myocardial perfusion imaging; myocardial blood flow reserve; positron emission tomography; adenosine; ticagrelor; clopidogrel

Outcome Measures

Primary Outcomes (1)

• Differences in rest MBF, stress MBF and MBFR between ticagrelor and clopidogrel treated patients as measured by PET

  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.

  q 2 weeks blood flow measurements

Secondary Outcomes (1)

• 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

  q 2 weeks blood flow measurements

Study Arms (2)

stable CAD management

EXPERIMENTAL

Experimental: Ticagrelor (BrilintaTM) 90 mg tablet by mouth twice a day

Drug: Ticagrelor; Drug: Clopidogrel

CAD comparison group

ACTIVE COMPARATOR

Active comparator: clopidogrel 75 mg plus placebo tablet by mouth twice a day.

Drug: Ticagrelor; Drug: Clopidogrel

Interventions

Ticagrelor DRUG

Blinded administration of ticagrelor for 10 days

Also known as: BrilintaTM

CAD comparison group; stable CAD management

Clopidogrel DRUG

Blinded administration of clopidogrel and placebo for 10 days

CAD comparison group; stable CAD management

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old
• Stable coronary artery disease on stable medical treatment.
• BMI equal to or less than 30 kg/m2
• No clinically significant abnormalities in baseline laboratory work
• No clinically significant arrhythmias on baseline 12-lead electrocardiogram
• 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.

You may not qualify if:

• Any contraindication against the use of clopidogrel, ticagrelor and/or ASA.
• Oral anticoagulation therapy.
• History of intracranial bleeding.
• Recent or active pathological bleeding, such as peptic ulcer.
• Moderate or severe hepatic impairment.
• History or risk of bradycardia.
• Known second- or third-degree AV block without pacemaker
• Dyspnea (NYHA III/IV), wheezing asthma or COPD.
• Coronary artery bypass graft (CABG) surgery within 90 days prior to screening or at any time after consent.
• Percutaneous coronary intervention (PCI) within 90 days prior to screening or at any time following consent.
• Acute myocardial infarction or acute coronary syndrome within 60 days prior to screening or at any time following consent.
• Any scheduled surgery during the trial period, including dental.
• Concomitant therapy with strong cytochrome CYP 3A inhibitor or inducer.
• Recent use of dipyridamole, dipyridamole-containing medications (e.g. Aggrenox)
• Known hypersensitivity to the investigational drug or any of its components.

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Related Publications (1)

• Pelletier-Galarneau M, Hunter CRRN, Ascah KJ, Beanlands RSB, Dwivedi G, deKemp RA, Chow BJW, Ruddy TD. Randomized Trial Comparing the Effects of Ticagrelor Versus Clopidogrel on Myocardial Perfusion in Patients With Coronary Artery Disease. J Am Heart Assoc. 2017 May 2;6(5):e005894. doi: 10.1161/JAHA.117.005894.

  PMID: 28465300 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Ticagrelor; Clopidogrel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Terrence Ruddy, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Terrence Ruddy

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: July 10, 2013
• Study Start: March 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: April 24, 2017

Record last verified: 2017-04

Locations

CA (1)