Clinical trial NCT01957540: Differential Effect of Ticagrelor Versus Prasugrel Maintenance Dose on Endothelial Function of Peripheral Vessels in Patients With Coronary Artery Disease
Official title: Differential Effect of Ticagrelor Versus Prasugrel Maintenance Dose on Endothelial Function of Peripheral Vessels in Patients With Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Endothelial Function
Keywords: ticagrelor
prasugrel
endothelial function
Lead sponsor: University of Patras
Sponsor class: OTHER
First posted: 2013-10-08
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Ticagrelor administration, whose molecule resembles to adenosine, led to reduction in overall mortality and thrombotic cardiovascular (CV) events when directly compared to clopidogrel in the PLATO trial, implicating possible pleiotropic actions for the drug. 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. Recent studies in healthy volunteers and patients with coronary artery disease (CAD) have shown that ticagrelor increases the coronary blood flow in response to intravenous adenosine administration. Ticagrelor administration, in comparison with other P2Y12 inhibitors, may influence the endothelial function, as assessed by the Peripheral Arterial Tonometry method (EndoPAT 2000 system (Itamar Medical, Caesarea, Israel), which is a method for evaluating endothelial dysfunction and has been found to positively correlate with flow mediated dilatation (FMD).

This is prospective, randomized study with a crossover design, which will be conducted in patients with CAD under prasugrel maintenance dose (MD) 10mg once a day for at least a 3-month period. At Day 0 (day of randomization) eligible patients will be assigned to either:

* Ticagrelor 90mg twice a day for the next 15 days or
* Prasugrel 10mg once a day for the next 15 days At Day 0 (before treatment onset)patients wiil be subjected to a baseline peripheral arterial tonometry measurement. Measurement will be repeated at Day 15 and then treatment crossover will be performed for the next 15 days (without an intervening washout period). At Day 30 patients will be subjected again to peripheral arterial tonometry assessment. Peripheral blood sample will be taken from the patients in Day 0 for genotyping control.


Eligibility criteria: Inclusion Criteria:

1. Age 18-74 years old
2. Patients with stable CAD who have been submitted(?) to percutaneous intervention for Acute Coronary Syndrome and receiving prasugrel MD 10mg once a day for at least the previous 3 months.
3. Patients giving written Informed Consent.

Exclusion Criteria:

1. Acute Coronary Syndrome
2. Contraindication for administration of prasugrel or ticagrelor

   1. Known hypersensitivity to clopidogrel or ticagrelor
   2. Active bleeding (peptic ulcer, intracranial bleeding)
   3. Severe liver impairment
   4. Any previous history of intracranial bleeding or transient ischemic attack or ischemic cerebrovascular event
   5. Treatment with potent CYP3A4 inhibitors (ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir)
3. Requirement for oral anticoagulant agents prior to the day 30 visit
4. History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months
5. Increased risk for bradyarrhythmias, according to the investigator's evaluation
6. Severe non-controlled chronic obstructive pulmonary disease
7. Creatinine clearance \<30ml/min/1.73mm2
8. HbA1c \> 10mg/dl

Primary outcomes:
measure: Reactive Hyperemia Index (RHI) in the 2 subgroups at the end of 2 periods of treatment
timeFrame: 15 days
Secondary outcomes:
measure: Percentage of patients with endothelial dysfunction (RHI<1.67) at the end of 2 periods of treatment
timeFrame: 15 days
Other outcomes:
Locations:
city: Patras
country: Greece
facility: Patras University Hospital
state: Achaia
Study officials:
References:
citation: Xanthopoulou I, Bei I, Bampouri T, Barampoutis N, Moulias A, Davlouros P, Alexopoulos D. Absence of differential effect of ticagrelor versus prasugrel maintenance dose on endothelial function in patients with stable coronary artery disease. Hellenic J Cardiol. 2018 Nov-Dec;59(6):338-343. doi: 10.1016/j.hjc.2017.12.008. Epub 2017 Dec 29.