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

This study is not yet open for participant recruitment.
Verified December 2012 by University of Texas Southwestern Medical Center
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
James De Lemos, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01743937
First received: December 3, 2012
Last updated: December 4, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Ischemic Preconditioning
Procedure: Coronary occlusion with balloon inflation
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Open Label Trial Comparing the Ischemic Preconditioning Effects of Ticagrelor and Clopidogrel in Humans

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Degree of ST-segment elevation by intracoronary ECG during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Degree of ST-segment elevation by surface ECG during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ] [ Designated as safety issue: No ]
  • Maximum inflation time tolerated following coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Angina score during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Strain rate on chest wall echocardiography before and during coronary balloon inflation [ Time Frame: 7-12 days after drug randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: January 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ticagrelor
Coronary occlusion with balloon inflation
Procedure: Coronary occlusion with balloon inflation
Active Comparator: Clopidogrel
Coronary occlusion with balloon inflation
Procedure: Coronary occlusion with balloon inflation

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01743937

Contacts
Contact: Michael Luna, MD 214-590-5028 michael.luna@utsouthwestern.edu
Contact: James de Lemos, MD 214-645-7521 james.delemos@utsouthwestern.edu

Locations
United States, Texas
Dallas Veterans Affairs Medical Center Not yet recruiting
Dallas, Texas, United States, 75216
Contact: Michael Luna, MD    214-590-5028    michael.luna@utsouthwestern.edu   
Principal Investigator: Jeff Hastings, MD, MS         
UT Southwestern Medical Center Not yet recruiting
Dallas, Texas, United States, 75390
Contact: Michael Luna, MD    214-590-5028    michael.luna@utsouthwestern.edu   
Contact: James de Lemos, MD    214-645-7521    james.delemos@utsouthwestern.edu   
Principal Investigator: Michael Luna, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
AstraZeneca
Investigators
Principal Investigator: James de Lemos, MD UT Southwestern Medical Center
  More Information

No publications provided

Responsible Party: James De Lemos, Professor of Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01743937     History of Changes
Other Study ID Numbers: AZUTSW
Study First Received: December 3, 2012
Last Updated: December 4, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
Ischemic preconditioning
Ticagrelor
Antiplatelet therapy
Acute coronary syndrome

Additional relevant MeSH terms:
Ischemia
Pathologic Processes
Clopidogrel
Ticagrelor
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014