Clinical trial NCT01743937: A Trial Comparing the Ischemic Preconditioning Effects of Ticagrelor and Clopidogrel in Humans
Official title: A Randomized, Controlled, Open Label Trial Comparing the Ischemic Preconditioning Effects of Ticagrelor and Clopidogrel in Humans
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Ischemic Preconditioning
Keywords: Ischemic preconditioning
Ticagrelor
Antiplatelet therapy
Acute coronary syndrome
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2012-12-06
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Degree of ST-segment elevation by intracoronary ECG during coronary balloon inflation
timeFrame: 7-12 days after drug randomization
Secondary outcomes:
measure: Degree of ST-segment elevation by surface ECG during coronary balloon inflation
timeFrame: 7-12 days after drug randomization
measure: Maximum inflation time tolerated following coronary balloon inflation
timeFrame: 7-12 days after drug randomization
measure: Time to ST-segment elevation during coronary balloon inflation
timeFrame: 7-12 days after drug randomization
measure: Angina score during coronary balloon inflation
timeFrame: 7-12 days after drug randomization
measure: Wall motion on chest wall echocardiography before and during coronary balloon inflation
timeFrame: 7-12 days after drug randomization
measure: Strain rate on chest wall echocardiography before and during coronary balloon inflation
timeFrame: 7-12 days after drug randomization
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Dallas Veterans Affairs Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: James de Lemos, MD
role: PRINCIPAL_INVESTIGATOR
References: