A Trial Comparing the Ischemic Preconditioning Effects of Ticagrelor and Clopidogrel in Humans
| Status: | Terminated |
|---|---|
| Conditions: | Peripheral Vascular Disease |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 74 |
| Updated: | 5/20/2018 |
| Start Date: | January 2013 |
| End Date: | December 2017 |
A Randomized, Controlled, Open Label Trial Comparing the Ischemic Preconditioning Effects of Ticagrelor and Clopidogrel in Humans
Antiplatelet therapy remains a cornerstone in the treatment of acute and chronic coronary
artery disease. Aspirin was the first such therapy to prove its benefits in acute myocardial
infarction. Compared to aspirin monotherapy, the combination of aspirin and clopidogrel, a
thienopyridine P2Y12 inhibitor, has been demonstrated to reduce adverse event rates among
patients with acute coronary syndromes (with or without ST-segment elevation) and those
receiving intracoronary stents. In the Triton-TIMI 38 trial a novel thienopyridine,
prasugrel, was compared to clopidogrel in patients with acute coronary syndrome undergoing
percutaneous coronary intervention. Although prasugrel significantly reduced recurrent
myocardial infarction, bleeding rates were increased and no improvement in cardiac or
all-cause mortality was demonstrated. However, in 2009, the authors of the PLATO trial
demonstrated an unexpected cardiovascular mortality benefit with ticagrelor over clopidogrel,
an endpoint not previously met by any other antiplatelet agent against an active comparator.
Based on the reproducible adverse events seen in the DISPERSE, DISPERSE-2, and PLATO trials,
an adenosine-mediated effect of ticagrelor is proposed.
Hypothesis: The aim of this study is to test the hypothesis that ticagrelor produces
pharmacologic ischemic preconditioning, an undescribed potential off-label property of
ticagrelor that could represent a plausible mechanism for its effects on cardiovascular
mortality.
artery disease. Aspirin was the first such therapy to prove its benefits in acute myocardial
infarction. Compared to aspirin monotherapy, the combination of aspirin and clopidogrel, a
thienopyridine P2Y12 inhibitor, has been demonstrated to reduce adverse event rates among
patients with acute coronary syndromes (with or without ST-segment elevation) and those
receiving intracoronary stents. In the Triton-TIMI 38 trial a novel thienopyridine,
prasugrel, was compared to clopidogrel in patients with acute coronary syndrome undergoing
percutaneous coronary intervention. Although prasugrel significantly reduced recurrent
myocardial infarction, bleeding rates were increased and no improvement in cardiac or
all-cause mortality was demonstrated. However, in 2009, the authors of the PLATO trial
demonstrated an unexpected cardiovascular mortality benefit with ticagrelor over clopidogrel,
an endpoint not previously met by any other antiplatelet agent against an active comparator.
Based on the reproducible adverse events seen in the DISPERSE, DISPERSE-2, and PLATO trials,
an adenosine-mediated effect of ticagrelor is proposed.
Hypothesis: The aim of this study is to test the hypothesis that ticagrelor produces
pharmacologic ischemic preconditioning, an undescribed potential off-label property of
ticagrelor that could represent a plausible mechanism for its effects on cardiovascular
mortality.
Inclusion Criteria:
- Undergoing clinically-indicated PCI for stable or progressive exertional angina
without rest angina, ST-segment shift, or elevated CK-MB or troponin-T or I
- Willing and able to give informed consent and to comply with study procedures
- Found to have single or two-vessel obstructive, non-occlusive (≥ 70% but < 100%
stenosis), coronary artery disease with plans for treatment of all lesions by PCI
- Target lesion location in the proximal or mid coronary vessel with reference diameter
≥ 2.5 mm
Exclusion Criteria:
- Known allergy to aspirin, clopidogrel, or ticagrelor
- Need for concomitant cardiac procedure, such as valve repair or replacement
- Age ≥ 75
- Concomitant theophylline/aminophylline use
- Baseline ECG with infarct or conduction abnormalities (i.e. LVH with repolarization
abnormality, bundle branch block, ST-segment abnormalities)
- Presenting with an ST-segment elevation or non ST-segment elevation myocardial
infarction
- Evidence of prior myocardial infarction by cardiac imaging
- Depressed left ventricular systolic function (ejection fraction < 50%)
- Clinical congestive heart failure
- End-stage renal disease
- Presence of coronary collaterals on diagnostic coronary angiography
- Presence of coronary thrombus on diagnostic coronary angiography
- Diffuse obstructive disease (≥ 70% stenosis) in the distal segment of the target
vessel
- Left main and/or three-vessel coronary artery disease
- Concomitant need for Warfarin therapy
We found this trial at
2
sites
2201 Inwood Rd
Dallas, Texas 75235
Dallas, Texas 75235
(214) 645-8300
Principal Investigator: Michael Luna, MD
Phone: 214-590-5028
U.T. Southwestern Medical Center The story of UT Southwestern Medical Center is one of commitment...
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Dallas, Texas 75216
Principal Investigator: Jeff Hastings, MD, MS
Phone: 214-590-5028
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