Clinical trial NCT02108808: Effect of Ticagrelor on Fractional Flow Reserve
Official title: Differential Effect of Ticagrelor vs Prasugrel or Clopidogrel Loading on Fractional Flow Reserve
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fractional Flow Reserve
Keywords: FFR
adenosine
Ticagrelor
Lead sponsor: University of Patras
Sponsor class: OTHER
First posted: 2014-04-09
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Fractional flow reserve (FFR) is an established invasive method for assessing the physiological significance of coronary artery stenosis. Adenosine, an important endogenous regulator of coronary blood flow during both stress and ischemia, is widely used to achieve conditions of stable hyperemia required for measurement of FFR.

Studies in healthy volunteers and in patients with acute coronary syndrome (ACS) post percutaneous coronary intervention (PCI) receiving ticagrelor revealed a differential coronary blood flow velocity response during increasing doses of adenosine compared to placebo or prasugrel treated subjects, respectively. It has also been demonstrated that patients treated with ticagrelor have increased plasma adenosine levels. Therefore, it has been hypothesized that the degree of hyperemia obtained with adenosine infusion may be greater in patients on ticagrelor than that obtained in patients taking clopidogrel or prasugrel. If this proves to be true, it would lead to a lower FFR value with possible important clinical implications in ticagrelor receiving patients in need for FFR measurement.

This is a prospective, single center, randomized study of parallel design. Consecutive ticagrelor naive patients who are referred for coronary angiography and have an angiographically moderate to severe de novo stenosis (\>50% and \<90% diameter by visual assessment) in at least one major epicardial coronary artery amenable to PCI are candidates for this study. Patients after informed consent will be randomized (hour 0) to receive immediately post FFR (with adenosine iintravenous infusion at 140 μg/Kg/min for a 3 minute period) either ticagrelor 180mg loading dose or prasugrel 60mg/clopidogrel 600mg loading dose (as clinically indicated). FFR examination will be repeated 2 hours post loading dose.


Eligibility criteria: Inclusion Criteria:

1. Age 18-80 years
2. Patients subjected to clinically indicated coronary angiography with at least one 50%-90% stenosis at 1 major epicardial vessel (by visual assessment) amenable to percutaneous coronary intervention.
3. Ticagrelor naive patients
4. Written informed consent

Exclusion Criteria:

1. History of coronary artery bypass surgery
2. Acute myocardial infarction within the previous 5 days
3. Known allergy to adenosine, ticagrelor, prasugrel or clopidogrel
4. Prior intracranial hemorrhage
5. Hemodialysis or creatinine clearance \< 30ml/h
6. Moderate/severe hepatic failure
7. Active bleeding, or at increased risk of bleeding
8. Left ventricular ejection fraction \<40%
9. Primary myocardial or valvular disease
10. Contraindication to adenosine
11. Angiographically visible thrombus at a target lesion, extremely tortuous coronary arteries, severely calcified lesions, left main disease, anatomy suitable for coronary artery bypass surgery
12. Previous q wave myocardial infarction in the area of target vessel
13. Severe left ventricular hypertrophy
14. Severe valvular heart disease
15. Heart failure as defined by New York Heart Association class III or IV 16.Hypotension (blood pressure \<90 mm Hg)

17.Significant arrhythmia (e.g. excessive premature ventricular contractions or atrial fibrillation), tachycardia (heart rate \>120 beats/min), bradycardia (\<50 beats/min), increased risk for bradycardia 18.Caffeine consumption or cigarette smoking within the previous 24 hours.

Primary outcomes:
measure: % relative change in steady hyperemia FFR (sFFR)
timeFrame: 2 hours
Secondary outcomes:
measure: % relative change in peak hyperemia FFR (pFFR)
timeFrame: 2 hours
measure: % relative change in lowest FFR (lFFR)
timeFrame: 2 hours
measure: % relative change in time to peak FFR (in seconds)
timeFrame: 2 hours
measure: % relative change in time to lowest FFR
timeFrame: 2 hours
measure: % relative change in area under the curve (AUC) of the FFR trace
timeFrame: 2 hours
Other outcomes:
measure: Reclassification of coronary revascularization strategy at hour 2 in relation to hour 0
timeFrame: 2 hours
Locations:
city: Patras
country: Greece
facility: Patras University Hospital
state: Achaia
Study officials:
References: