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

NCT01700322 | Completed Phase 4 DMC

• 1 other identifier: CTH-C1
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Artery Disease

Keywords

Coronary artery disease; coronary stenting; platelet aggregation

Outcome Measures

Primary Outcomes (1)

• Change in FMD

  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.

  baseline and 1 month

Secondary Outcomes (4)

• FMD 2 hours after loading dose

  baseline and 2 hours after loading dose

• L-FMC at 2 hours after the loading dose

  baseline and 2 hours

• L-FMC 1 month after loading dose

  baseline and 1 day after stenting

• Safety and tolerability

  from baseline to 1 month after enrollment

Study Arms (3)

Ticagrelor

ACTIVE COMPARATOR

Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting

Procedure: Coronary stenting; Drug: Ticagrelor

Clopidogrel

ACTIVE COMPARATOR

Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting.

Procedure: Coronary stenting; Drug: Clopidogrel

Prasugrel

ACTIVE COMPARATOR

Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting

Procedure: Coronary stenting; Drug: Prasugrel

Interventions

Coronary stenting PROCEDURE

All patients will receive a drug eluting stent as clinically indicated.

Clopidogrel; Prasugrel; Ticagrelor

Ticagrelor DRUG

Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting

Ticagrelor

Clopidogrel DRUG

Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting.

Clopidogrel

Prasugrel DRUG

Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting

Prasugrel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johannes Gutenberg University Mainz: lead

Study Sites (1)

2 Medical Clinic

Mainz, 55131, Germany

Location

Related Publications (2)

• Schnorbus B, Jurk K, Lackner KJ, Welk C, Munzel T, Gori T. Effects of Clopidogrel, Prasugrel and Ticagrelor on Microvascular Function and Platelet Reactivity in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Stenting. A Randomized, Blinded, Parallel Group Trial. Front Cardiovasc Med. 2021 Dec 13;8:780605. doi: 10.3389/fcvm.2021.780605. eCollection 2021.

  PMID: 34966798 DERIVED

• Schnorbus B, Daiber A, Jurk K, Warnke S, Konig J, Krahn U, Lackner K, Munzel T, Gori T. Effects of clopidogrel, prasugrel and ticagrelor on endothelial function, inflammatory and oxidative stress parameters and platelet function in patients undergoing coronary artery stenting for an acute coronary syndrome. A randomised, prospective, controlled study. BMJ Open. 2014 May 6;4(5):e005268. doi: 10.1136/bmjopen-2014-005268.

  PMID: 24801283 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Ticagrelor; Clopidogrel; Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Piperazines

Study Officials

• Thomas Munzel, MD Prof.

  University Medical Center Mainz

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 4, 2012
• First Posted: October 4, 2012
• Study Start: August 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 7, 2016

Record last verified: 2016-09

Locations

DE (1)