Clinical trial NCT01161121: Comparison of Intravenous Adenosine Infusion With Regadenoson Bolus for Inducing Maximal Coronary Hyperemia
Official title: Utilization of Lexiscan (Regadenoson)in the Cardiac Catheterization Lab to Achieve Maximal Hyperemia for Coronary Physiologic Assessment With Fractional Flow Reserve
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Coronary Artery Disease
Keywords: Fractional flow reserve
adenosine
regadenoson
Lead sponsor: St. Louis University
Sponsor class: OTHER
Collaborators: name: University of Florida
name: Astellas Pharma US, Inc.
First posted: 2010-07-13
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to determine if regadenoson is as safe and effective as adenosine when used in the cardiac catheterization lab during measurement of coronary flow reserve and fractional flow reserve. The study hypothesis is the assessment of Fractional Flow Reserve (FFR) in the catheterization lab can be performed with equivalent accuracy when hyperemia is induced with IV Regadenoson compared with IV Adenosine without compromising patient safety.

Detailed description: Patients with clinical indications to be assessed by fractional flow reserve (FFR) will be included. Following diagnostic angiography in the catheterization lab, the patient will have a guide catheter placed in the artery to be assessed followed by placing a pressure guidewire down the coronary vessel and past the lesion of interest. FFR will be measured in the traditional manner, with intravenous adenosine infusing at 140 mcg/kg/min until maximal steady state hyperemia is reached. At this point, the FFR will be recorded as Pd (distal pressure from the pressure wire in the coronary artery) divided by Pa (proximal pressure from the guide catheter). The adenosine infusion will then be stopped and the patient's hemodynamics allowed to return to baseline. Once baseline state is again achieved, an intravenous bolus of regadenson (0.4 mg) will be given and FFR will be remeasured as the lowest steady state Pd/Pa. Patients will be enrolled at two sites, The University of Florida - where FFR will be measured alone, and Saint Louis University, where coronary flow will be measured simultaneously to evaluate the effect of regadenoson on coronary flow velocity as compared to adenosine. The primary endpoint of the study will be to compare the FFR achieved with adeonsine to that obtained with regadenoson.

Eligibility criteria: Inclusion Criteria:

* male or female patients greater than 18 years old (If female, pt. must be post-menopausal, surgically sterile, or be non-pregnant as determined by a negative urine or serum beta human chorionic gonadotropin (B-HCG) pregnancy test within 24 hours prior to enrollment.
* Provided written consent approved by Institutional Review Board and provided Health Insurance Portability and Accountability Act (HIPAA) authorization
* Have at least one coronary stenosis (greater or equal to 40% but less than 70\& narrowing by visual inspection) and technically accessible coronary artery into which the pressure wire may be introduced.

Exclusion Criteria:

* ST elevation myocardial infarction
* Cardiogenic shock
* Pregnancy
* Total vessel occlusion
* Extremely tortuous coronary arteries
* Second and third degree heart block without pacemaker
* Severe chronic obstructive pulmonary disease and active bronchospasm
* Less than age 18 years
* Have received theophylline, aminophylline, pentoxifylline or dipyridamole within 12 hours of FFR measurement.
* Has severe 3 vessel disease defined by \>80% luminal narrowing by visual inspection
* Known hypersensitivity to adenosine or regadenoson
* Recent uncontrolled ventricular arrhythmia
* History of greater than Type I atrioventricular block, symptomatic resting bradycardia, sick sinus syndrome (without permanent pacemaker)
* History of heart transplantation

Primary outcomes:
measure: Difference in FFR Between IV Adenosine and IV Regadenoson
timeFrame: At maximal, steady-state hyperemia
Secondary outcomes:
measure: Heart Rate Changes With Drug
timeFrame: During drug infusion and until restoration of baseline hemodynamics
measure: Side Effects of Medication Administration
timeFrame: During drug infusion and until restoration of baseline hemodynamics
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
Study officials:
affiliation: St. Louis University
name: Michael J Lim, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pijls NH, Van Gelder B, Van der Voort P, Peels K, Bracke FA, Bonnier HJ, el Gamal MI. Fractional flow reserve. A useful index to evaluate the influence of an epicardial coronary stenosis on myocardial blood flow. Circulation. 1995 Dec 1;92(11):3183-93. doi: 10.1161/01.cir.92.11.3183.
citation: Iskandrian AE, Bateman TM, Belardinelli L, Blackburn B, Cerqueira MD, Hendel RC, Lieu H, Mahmarian JJ, Olmsted A, Underwood SR, Vitola J, Wang W; ADVANCE MPI Investigators. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial. J Nucl Cardiol. 2007 Sep-Oct;14(5):645-58. doi: 10.1016/j.nuclcard.2007.06.114.
citation: Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009 Jan 15;360(3):213-24. doi: 10.1056/NEJMoa0807611.
citation: Lim MJ, Kern MJ. Coronary pathophysiology in the cardiac catheterization laboratory. Curr Probl Cardiol. 2006 Aug;31(8):493-550. doi: 10.1016/j.cpcardiol.2006.04.002.
citation: Stolker JM, Lim MJ, Shavelle DM, Morris DL, Angiolillo DJ, Guzman LA, Kennedy KF, Weber E, Zareh M, Neumayr RH, Zenni MM. Pooled comparison of regadenoson versus adenosine for measuring fractional flow reserve and coronary flow in the catheterization laboratory. Cardiovasc Revasc Med. 2015 Jul-Aug;16(5):266-71. doi: 10.1016/j.carrev.2015.05.011. Epub 2015 Jun 5.