Endothelium, Stenting, and Antiplatelet Therapy (EST) - Clopidogrel, Prasugrel, Ticagrelor Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Johannes Gutenberg University Mainz
Sponsor:
Information provided by (Responsible Party):
Tommaso Gori, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier:
NCT01700322
First received: September 4, 2012
Last updated: March 16, 2014
Last verified: March 2014
  Purpose

Endothelial dysfunction is an important predictor - and a determinant - of adverse clinical outcome. Endothelial function is impaired by coronary artery stenting, a stud from our group has shown that it can be improved by platelet inhibition using clopidogrel. However, clopidogrel unresponsiveness is a known problem, and it has been show that the endothelial effects of clopidogrel tend to wane upon prolonged treatment. Whether a more effective anti-platelet therapy is able to prevent/improve not only thrombotic events but also endothelial dysfunction, with potential positive impact on clinical outcome in patients undergoing coronary artery stenting, is an important hypothesis that needs to be further investigated. To date, evidence regarding "ancillary" (non-platelet-dependent) effects of antiaggregant drugs is very limited. For instance, while their antiplatelet effects, and their beneficial effects in patients with acute coronary syndromes, have been clearly demonstrated in multicentric trials, it remains to be shown whether these drugs also protect endothelial function. Interestingly, some authors suggest that the mortality benefit observed in the PLATO study is at least in part independent of direct antiplatelet effects. No study, to date, has tested the effects of prasugrel and/or ticagrelor on endothelial function. With the present trial, the investigators plan to test the effect of clopidogrel, prasugrel and ticagrelor on endothelial function before and up to 4 weeks after coronary artery stenting. This study will provide important pathophysiologic insight on the relationship between platelet aggregation and endothelial function, two parameters that have been shown to influence patients' prognosis.


Condition Intervention Phase
Coronary Artery Disease
Procedure: Coronary stenting
Drug: Ticagrelor
Drug: Clopidogrel
Drug: Prasugrel
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Basic Science
Official Title: Effects of Clopidogrel vs Prasugel vs Ticagrelor on Endothelial Function, Inflammatory and Oxidative Stress Parameters and Platelet Function in Patients Undergoing Coronary Artery Stenting. A Randomised, Prospective Study.

Resource links provided by NLM:


Further study details as provided by Johannes Gutenberg University Mainz:

Primary Outcome Measures:
  • Change in FMD [ Time Frame: baseline and 1 month ] [ Designated as safety issue: No ]
    The primary endpoint is the change in flow-mediated dilation (FMD) (comparison before treatment versus after treatment and stenting) in the three study groups. The mean FMD across the three measurements (1 day, 1 week, 1 month) performed after coronary artery stenting will be compared to the FMD value before drug administration and stenting.


Secondary Outcome Measures:
  • FMD 2 hours after loading dose [ Time Frame: baseline and 2 hours after loading dose ] [ Designated as safety issue: No ]
    Change in FMD 2 hours after the administration of the study drug

  • L-FMC at 2 hours after the loading dose [ Time Frame: baseline and 2 hours ] [ Designated as safety issue: No ]
    change in L-FMC at two hours after the loading dose

  • L-FMC 1 month after loading dose [ Time Frame: baseline and 1 day after stenting ] [ Designated as safety issue: No ]
    change in flow-mediated constriction (L-FMC) (comparison before treatment versus after treatment and stenting) in the three study groups. The mean L-FMC across the three measurements (1 day, 1 week, 1 month) performed after coronary artery stenting will be compared to the value before drug administration and stenting

  • Safety and tolerability [ Time Frame: from baseline to 1 month after enrollment ] [ Designated as safety issue: Yes ]
    Number of patients with adverse events.


Estimated Enrollment: 180
Study Start Date: August 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ticagrelor
Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting
Procedure: Coronary stenting
All patients will receive a drug eluting stent as clinically indicated.
Drug: Ticagrelor
Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting
Active Comparator: Clopidogrel
Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting.
Procedure: Coronary stenting
All patients will receive a drug eluting stent as clinically indicated.
Drug: Clopidogrel
Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting.
Active Comparator: Prasugrel
Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting
Procedure: Coronary stenting
All patients will receive a drug eluting stent as clinically indicated.
Drug: Prasugrel
Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • - 18-75 years old consecutive patients undergoing coronary angiography and stenting at the University Medical Centre Mainz
  • A coronary lesion (and patient) amenable to treatment with drug eluting stent
  • Ability of subject to understand character and individual consequences of clinical trial
  • Signed and dated informed consent of the subject must be available before start of any specific trial procedures.
  • Negative pregnancy test of women with childbearing potential

Exclusion Criteria:

  • Subjects presenting 1 or more of the following criteria will not be enrolled in the trial:
  • Patients with elevated (> 5 times upper normal limit) C-reactive protein level prior to stenting
  • Patients in whom therapy with long-acting nitrates cannot be suspended prior to endothelial function measurements
  • An acute coronary syndrome treated with coronary stenting within the last 4 weeks
  • Patients with known inflammatory/infective diseases
  • Patients with severe extracardiac diseases limiting life expectancy
  • Known heart failure (LV-EF ≤ 40% AND NYHA III-IV)
  • PCI or coronary By-Pass surgery within the last 4 weeks, pre-existing ongoing treatment with any of the study treatments.
  • History of cerebrovascular events (stroke)
  • Known renal dysfunction (serum creatinine ≥ 1.8mg/dl in women, ≥ 2.0mg/dl in men)
  • Serum potassium > 5.5mmol/l
  • Known hepatic impairment (AST, ALT > 3 times upper limit of normal)
  • Changes in the ß-blocker, statin or ACE or angiotensin-receptor blocker inhibitor treatment within the past 2 weeks
  • Pregnancy and lactation, inadequate contraception
  • Body weight < 60kg
  • Active bleeding
  • Therapy with CYP3A4 inhibitors (ketoconazole, protease inhibitors, macrolide antibiotics)
  • Therapy with anticoagulants: phenprocoumone, warfarin, dabigatran, rivaroxaban
  • History of hypersensitivity to any of the investigational medicinal products or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
  • Ongoing participation in other clinical trials or within the last 3 months, or ongoing therapy with one of the study medications.
  • Medical or psychological condition that would not permit completion of the trial or signing of informed consent.
  • Patients with acute ST-elevation myocardial infarction
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01700322

Contacts
Contact: Tommaso Gori, MD PhD +496131172829 tommaso.gori@unimedizin-mainz.de

Locations
Germany
2 Medical Clinic Recruiting
Mainz, Germany, 55131
Principal Investigator: Thomas Münzel, MD         
Sub-Investigator: Boris Schnorbus, MD         
Sponsors and Collaborators
Johannes Gutenberg University Mainz
Investigators
Study Chair: Thomas Munzel, MD Prof. University Medical Center Mainz
  More Information

No publications provided

Responsible Party: Tommaso Gori, Professor, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier: NCT01700322     History of Changes
Other Study ID Numbers: CTH-C1
Study First Received: September 4, 2012
Last Updated: March 16, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Johannes Gutenberg University Mainz:
Coronary artery disease
coronary stenting
platelet aggregation

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Clopidogrel
Ticlopidine
Ticagrelor
Prasugrel
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
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 18, 2014