Back to results

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

Primary Purpose

Coronary Artery Disease

Status

Completed

Phase

Phase 4

Locations

Germany

Study Type

Interventional

Intervention

Coronary stenting

Ticagrelor

Clopidogrel

Prasugrel

About this trial

This is an interventional basic science trial for Coronary Artery Disease focused on measuring Coronary artery disease, coronary stenting, platelet aggregation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

2 Medical Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Ticagrelor

Clopidogrel

Prasugrel

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

FMD 2 hours after loading dose

Change in FMD 2 hours after the administration of the study drug

L-FMC at 2 hours after the loading dose

change in L-FMC at two hours after the loading dose

L-FMC 1 month after loading dose

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

Number of patients with adverse events.

Full Information

NCT ID

NCT01700322

First Posted

September 4, 2012

Last Updated

September 4, 2016

Sponsor

Johannes Gutenberg University Mainz

1. Study Identification

Unique Protocol Identification Number

NCT01700322

Brief Title

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

Acronym

EST

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.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

August 2012 (undefined)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Johannes Gutenberg University Mainz

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronary Artery Disease

Keywords

Coronary artery disease, coronary stenting, platelet aggregation

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

126 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ticagrelor

Arm Type

Active Comparator

Arm Description

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

Arm Title

Clopidogrel

Arm Type

Active Comparator

Arm Description

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

Arm Title

Prasugrel

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Procedure

Intervention Name(s)

Coronary stenting

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ticagrelor

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Clopidogrel

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Prasugrel

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in FMD

Description

Time Frame

baseline and 1 month

Secondary Outcome Measure Information:

Title

FMD 2 hours after loading dose

Description

Change in FMD 2 hours after the administration of the study drug

Time Frame

baseline and 2 hours after loading dose

Title

L-FMC at 2 hours after the loading dose

Description

change in L-FMC at two hours after the loading dose

Time Frame

baseline and 2 hours

Title

L-FMC 1 month after loading dose

Description

Time Frame

baseline and 1 day after stenting

Title

Safety and tolerability

Description

Number of patients with adverse events.

Time Frame

from baseline to 1 month after enrollment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Munzel, MD Prof.

Organizational Affiliation

University Medical Center Mainz

Official's Role

Study Chair

Facility Information:

Facility Name

2 Medical Clinic

City

Mainz

ZIP/Postal Code

55131

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

34966798

Citation

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.

Results Reference

derived

PubMed Identifier

24801283

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs