Clinical trial NCT01642966: Differential Effect of Ticagrelor Versus Prasugrel on the Adenosine-induced Coronary Vasodilatory Responses in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: ticagrelor
doppler echocardiography
Lead sponsor: University of Patras
Sponsor class: OTHER
First posted: 2012-07-17
Enrollment: 56
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: 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 .


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 15 days
Secondary outcomes:
measure: 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
timeFrame: 15 days
measure: 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
timeFrame: 15 days
measure: 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
timeFrame: 15 days
measure: 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
timeFrame: 15 days
Other outcomes:
Locations:
city: Patras
country: Greece
facility: Cardiology Department Patras University Hospital
state: Achaia
Study officials:
References:
citation: Alexopoulos D, Moulias A, Koutsogiannis N, Xanthopoulou I, Kakkavas A, Mavronasiou E, Davlouros P, Hahalis G. Differential effect of ticagrelor versus prasugrel on coronary blood flow velocity in patients with non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention: an exploratory study. Circ Cardiovasc Interv. 2013 Jun;6(3):277-83. doi: 10.1161/CIRCINTERVENTIONS.113.000293. Epub 2013 Jun 4.