A Trial Comparing the Ischemic Preconditioning Effects of Ticagrelor and Clopidogrel in Humans (ETCH)

• ClinicalTrials.gov Identifier: NCT01743937
• Recruitment Status: Terminated
• First Posted: December 6, 2012
• Last Update Posted: November 25, 2020
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): James De Lemos, University of Texas Southwestern Medical Center

Tracking Information

• First Submitted Date: December 3, 2012
• First Posted Date: December 6, 2012
• Last Update Posted Date: November 25, 2020
• Study Start Date: January 2013
• Actual Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 4, 2012): Degree of ST-segment elevation by intracoronary ECG during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 4, 2012)

• Degree of ST-segment elevation by surface ECG during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ]
• Maximum inflation time tolerated following coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ]
  This is defined as the amount of time the patient tolerates having loss of coronary flow in the target coronary artery during balloon inflation.
• Time to ST-segment elevation during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ]
• Angina score during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ]
  This will be reported by the study subject during coronary balloon occlusion based on a validated pain scale.
• Wall motion on chest wall echocardiography before and during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ]
• Strain rate on chest wall echocardiography before and during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Ischemic Preconditioning
• Intervention: Procedure: Coronary occlusion with balloon inflation

Study Arms

• Active Comparator: Ticagrelor
  Coronary occlusion with balloon inflation
  Intervention: Procedure: Coronary occlusion with balloon inflation
• Active Comparator: Clopidogrel
  Coronary occlusion with balloon inflation
  Intervention: Procedure: Coronary occlusion with balloon inflation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 15, 2018): 18
• Original Estimated Enrollment (submitted: December 4, 2012): 50
• Actual Study Completion Date: December 2017
• Actual Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 74 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01743937
• Other Study ID Numbers: AZUTSW
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: James De Lemos, University of Texas Southwestern Medical Center
• Study Sponsor: University of Texas Southwestern Medical Center
• Collaborators: AstraZeneca

Investigators

• Principal Investigator: James de Lemos, MD; UT Southwestern Medical Center

• PRS Account: University of Texas Southwestern Medical Center
• Verification Date: November 2020