Peripheral Endothelial Function Assessment of Patients on Ticagrelor vs. Clopidogrel Who Have Undergone PCI

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ClinicalTrials.gov Identifier: NCT02469740

Recruitment Status : Completed

First Posted : June 11, 2015

Last Update Posted : March 11, 2016

Sponsor:

Information provided by (Responsible Party):

Ronstan Lobo, University Hospital of Limerick

Study Description

Brief Summary:

Usage of antiplatelet agents and cardiac procedures such as coronary angioplasty has dramatically improved the morbidity and mortality associated with coronary artery disease. In patients with a coronary stent, dual antiplatelet therapy is recommended. Aspirin is the main antiplatelet agent used. For many years, clopidogrel was the second antiplatelet of choice. Recent studies have revealed new antiplatelet drugs that can substitute clopidogrel, one of which is ticagrelor. The degree to which ticagrelor reduced the overall mortality compared to clopidogrel in the PLATO trial suggested that ticagrelor possibly has a pleiotropic effect and that the reduction in mortality is not simply due to its antiplatelet effects. The ticagrelor molecule resembles adenosine. Adenosine has been shown to be cardioprotective.

The aim of this project is to study the effects of ticagrelor on the arterial system using a noninvasive method. The study will employ the measurement of peripheral endothelial function of patients who undergo percutaneous coronary intervention who are on ticagrelor vs. clopidogrel using a cross over trial design.

Condition or disease	Intervention/treatment	Phase
Myocardial Ischemia Coronary Artery Disease Endothelial Dysfunction	Drug: Ticagrelor Drug: Clopidogrel	Phase 4

Detailed Description:

Cardiovascular disease remains the most common cause of death in Ireland. Usage of antiplatelet agents and cardiac procedures such as coronary angioplasty has dramatically improved the morbidity and mortality associated with coronary artery disease. In patients with a coronary stent, dual antiplatelet therapy is recommended. Aspirin is the main antiplatelet agent used. For many years, clopidogrel was the second antiplatelet of choice. Recent studies have revealed new antiplatelet drugs that can substitute clopidogrel, one of which is ticagrelor. Ticagrelor received approval from regulatory authorities such as the Food and Drug Administration and the European Medicines Agency based on the PLATO trial which demonstrated a reduction in overall mortality and thrombotic cardiovascular events when compared to clopidogrel. Ticagrelor is approved in Europe and specifically in Ireland for use in patients with ACS and in patients undergoing coronary angioplasty. The degree to which ticagrelor reduced the overall mortality compared to clopidogrel in the PLATO trial suggested that ticagrelor possibly has a pleiotropic effect and that the reduction in mortality is not simply due to its antiplatelet effects. The ticagrelor molecule resembles adenosine. It has been shown that ticagrelor increases adenosine concentration, by interfering with its red blood cells' uptake and by inducing the release of ATP which is then converted to adenosine. Adenosine has been shown to be cardioprotective.

Peripheral Arterial Tonometry (EndoPAT 2000 system (Itamar Medical, Caesarea, Israel) is a method for evaluating endothelial dysfunction. The device has received a CE mark (approved for use in Europe). It uses a non-invasive assessment called fingertip pulse amplitude tonometry.

The reactive hyperaemia response as detected by the reactive hyperaemia index (RHI) has been shown to be related to multiple traditional and metabolic risk factors. It has also been found to positively correlate with flow mediated dilatation (FMD) and coronary vasoreactivity as assessed by intracoronary acetylcholine. A significant advantage of the endoPAT device is the reproducibility of results when compared to FMD in assessment of peripheral endothelial function. Smaller studies have shown positive effects of ticagrelor on endothelial function assessment compared with clopidogrel or prasugrel but no randomised study has been done to date.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	61 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Peripheral Endothelial Function Assessment of Patients on Ticagrelor vs. Clopidogrel Who Have Undergone Percutaneous Coronary Intervention - a Randomised, Crossover Study.
Study Start Date :	July 2015
Actual Primary Completion Date :	January 2016
Actual Study Completion Date :	January 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Clopidogrel Clopidogrel bisulfate Ticagrelor

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ticagrelor Patients in this group will be prescribed ticagrelor 90 mg BD for 4 weeks.	Drug: Ticagrelor Patients that are randomly selected to receive ticagrelor during the first phase of the study will receive the dose of 90 mg BD orally. This will be continued for 4 weeks before the endothelial function test will be performed. If the patients are assigned in the 2nd phase of the study, they will receive 90 mg BD orally for 5 weeks (4 weeks plus a 1 week washout period). Other Name: Brilique
Active Comparator: Clopidogrel Patients in this group will be prescribed clopidogrel 75 mg OD for 4 weeks	Drug: Clopidogrel Patients that are randomly selected to receive ticagrelor during the first phase of the study will receive the dose of 75 mg OD orally. This will be continued for 4 weeks before the endothelial function test will be performed. If the patients are assigned in the 2nd phase of the study, they will receive 75 mg OD orally for 5 weeks (4 weeks plus a 1 week washout period). Other Name: Plavix, Clodel

Arm

Intervention/treatment

Experimental: Ticagrelor

Patients in this group will be prescribed ticagrelor 90 mg BD for 4 weeks.

Drug: Ticagrelor

Patients that are randomly selected to receive ticagrelor during the first phase of the study will receive the dose of 90 mg BD orally. This will be continued for 4 weeks before the endothelial function test will be performed. If the patients are assigned in the 2nd phase of the study, they will receive 90 mg BD orally for 5 weeks (4 weeks plus a 1 week washout period).

Other Name: Brilique

Active Comparator: Clopidogrel

Patients in this group will be prescribed clopidogrel 75 mg OD for 4 weeks

Drug: Clopidogrel

Patients that are randomly selected to receive ticagrelor during the first phase of the study will receive the dose of 75 mg OD orally. This will be continued for 4 weeks before the endothelial function test will be performed. If the patients are assigned in the 2nd phase of the study, they will receive 75 mg OD orally for 5 weeks (4 weeks plus a 1 week washout period).

Other Name: Plavix, Clodel

Outcome Measures

Primary Outcome Measures :

The number of patients with endothelial dysfunction (Reactive Hyperemia index of < 1.67 using the non-invasive Endo-PAT 2000 device) on ticagrelor versus clopidogrel. [ Time Frame: 9 weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol
Subjects must be male or female, aged 18 years or above at baseline
Diagnosed with coronary artery disease and undergone PCI
Female subjects of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 12 months (as per guidelines on patients undergoing PCI who are on antiplatelet therapy).
Female subjects' urine pregnancy test performed at the baseline visit must be negative (which is required by local hospital policy in order to undergo PCI).

Exclusion Criteria:

Allergy/hypersensitivity to study medications or their ingredients
Contraindications to either clopidogrel or ticagrelor:
- Ticagrelor contraindications - active bleeding, history of intracranial haemorrhage, moderate to severe hepatic impairment, dialysis, uric acid nephropathy, co-administration of a strong CYP3A4 inhibitor (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir), history of sick sinus syndrome or high degree AV block without pacemaker protection
- Clopidogrel contraindications - severe hepatic impairment, active bleeding
On treatment with oral anticoagulant (vitamin K antagonist, dabigatran, rivaroxaban, apixaban)
Unable to follow up in research centre (for example, due to logistic difficulties)
Female subjects who are pregnant or breast-feeding, or considering becoming pregnant during the study.
Subjects who have participated in another study and received any other investigational agent within the previous 12 months
Subjects unable to provide written informed consent within 24 hours of PCI (for example, intubated patients)
Subjects who have a history of drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements.
Use of both left and right radial access for PCI

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02469740

Locations

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Ireland
University Hospital Limerick
Dooradoyle, Limerick, Ireland

Sponsors and Collaborators

University Hospital of Limerick

Investigators

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Study Chair:	Thomas J Kiernan	University Hospital of Limerick

More Information

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Responsible Party:	Ronstan Lobo, MB, BCh, BAO (Hons), BMedSc (Hons), MRCPI, MRCP(UK), University Hospital of Limerick
ClinicalTrials.gov Identifier:	NCT02469740 History of Changes
Other Study ID Numbers:	RON004 2015-000334-30 ( EudraCT Number )
First Posted:	June 11, 2015 Key Record Dates
Last Update Posted:	March 11, 2016
Last Verified:	March 2016

Keywords provided by Ronstan Lobo, University Hospital of Limerick:


Ticagrelor Clopidogrel Coronary Artery Disease Percutaneous Coronary Intervention Acute Coronary Syndrome

Additional relevant MeSH terms:

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Coronary Artery Disease Myocardial Ischemia Coronary Disease Ischemia Heart Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Pathologic Processes	Clopidogrel Ticagrelor Platelet Aggregation Inhibitors Purinergic P2Y Receptor Antagonists Purinergic P2 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs

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