Differential Effect of Ticagrelor Versus Prasugrel on the Adenosine-induced Coronary Vasodilatory Responses in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Sponsor

University of Patras (Other)

Overall Status

Completed

CT.gov ID

NCT01642966

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

This is a prospective, randomized, single-blind, investigator-initiated, crossover study. Patients with Acute Coronary Syndrome (ACS) subjected to percutaneous coronary intervention (PCI), are randomized after informed consent, in a 1:1 ratio to either ticagrelor 90mg x2 or prasugrel 10mg x1 for 15 days. At Day 15± 2 days, coronary diastolic blood flow velocity in left anterior descending artery (LAD) is evaluated at baseline (bCBFV) and under 2 min adenosine infusions (maximal diastolic CBFV- maxCBFV) at gradually increasing doses of 50μg/kg/min, 80μg/kg/min, 110μg/kg/min and 140μg/kg/min with at least 5 min recovery intervals between infusions. A crossover directly to the alternate treatment is performed followed by the same evaluation at Day 30±2 days .

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Prasugrel Drug: Ticagrelor	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

56 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Differential Effect of Ticagrelor Versus Prasugrel on the Adenosine-induced Coronary Vasodilatory Responses in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Study Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Prasugrel Prasugrel 10mg/day for 15 days	Drug: Prasugrel Prasugrel 10mg/day for 15 days
Experimental: Ticagrelor Ticagrelor 90mg twice a day for 15 days	Drug: Ticagrelor Ticagrelor 90mg twice a day for 15 days

Arm

Intervention/Treatment

Active Comparator: Prasugrel

Prasugrel 10mg/day for 15 days

Drug: Prasugrel

Prasugrel 10mg/day for 15 days

Experimental: Ticagrelor

Ticagrelor 90mg twice a day for 15 days

Drug: Ticagrelor

Ticagrelor 90mg twice a day for 15 days

Outcome Measures

Primary Outcome Measures

The area under the curve (AUC) of the maxCBFV (maximal diastolic blood flow velocity in left anterior descending artery)at gradually increasing doses of adenosine [15 days]
The primary outcome will be assessed 15 days after the onset of each study drug

Secondary Outcome Measures

The ratio of maximal diastolic blood flow velocity in left anterior descending artery/baseline diastolic blood flow velocity in left anterior descending artery for 50μg/kg/min adenosine infusion at the end of treatment periods [15 days]
The ratio of maximal diastolic blood flow velocity in left anterior descending artery/baseline diastolic blood flow velocity in left anterior descending artery for 80μg/kg/min adenosine infusion at the end of treatment periods [15 days]
The ratio of maximal diastolic blood flow velocity in left anterior descending artery/baseline diastolic blood flow velocity in left anterior descending artery for 110μg/kg/min adenosine infusion at the end of treatment periods [15 days]
The ratio of maximal diastolic blood flow velocity in left anterior descending artery/baseline diastolic blood flow velocity in left anterior descending artery for 140μg/kg/min adenosine infusion at the end of treatment periods [15 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-74 years
Patients with acute coronary syndrome undergoing PCI with stenting
Sinus rhythm
Written informed consent

Exclusion Criteria:

Known hypersensitivity to prasugrel or ticagrelor
Requirement for oral anticoagulant prior to the Day 30 visit
Any previous history of ischemic stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm)
Any active bleeding or history of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months, other bleeding diathesis, or considered by investigator to be at high risk for bleeding
Concomitant oral or IV therapy with strong CY P3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazana vir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3A inducers (rifampin /rifampicin, phenytoin, carbamazepine).
Increased risk of bradycardiac events.
Dialysis required.
Severe uncontrolled chronic obstructive pulmonary disease
Known severe hepatic impairment
Pregnancy or breastfeeding
Left ventricular ejection fraction < 45%, severe left ventricular hypertrophy, diastolic dysfunction, severe valve disease
Prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass grafting
Weight < 60 Kg
Alcohol or narcotics abuse
Major periprocedural complications: death, cardiogenic shock, stent thrombosis, arrhythmias requiring cardioversion/defibrillation, temporary pacemaker insertion or intravenous antiarrhythmic agents, respiratory failure requiring intubation, retroperitoneal bleeding, major bleeding (need for blood transfusion or drop in haemoglobin post-PCI by ≥ 5 gr/ dl or intracranial bleeding), unsuccessful PCI (residual stenosis > 30% or flow < ΤΙΜΙ 3) or planned staged PCI in the next 5 days after randomization
Any residual stenosis > 40% in LAD
Small vessels or diffuse coronary atherosclerosis
Inability to detect coronary blood flow in LAD