Comparison of Intravenous Adenosine Infusion With Regadenoson Bolus for Inducing Maximal Coronary Hyperemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Utilization of Lexiscan (Regadenoson)in the Cardiac Catheterization Lab to Achieve Maximal Hyperemia for Coronary Physiologic Assessment With Fractional Flow Reserve

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: adenosine
* Drug: regadenoson


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adenosine then Regadenoson<br>Adenosine infusion will be compared to Regadenoson for efficacy and safety/side effects. Arterial blood pressure, coronary pressure, heart rate, oxygen saturation and coronary flow, FFR, and coronary flow velocity will be assessed. Safety will be assessed by monitoring for any side effects such as chest pain, headache, flushing, nausea, or arrhythmias. Adenosine infusion will be administered at 140 mcg/kg for 2 minutes and once mean coronary flow velocity returns to within 15% of pre-dose value, Regadenoson IV bolus 0.4 mg/5 ml will be administered followed by a 5 cc normal saline flush. | Drug: adenosine<br>* Measuring FFR and Coronary Flow Reserve after administration of IV adenosine 140 mcg/kg/min for 2 minutes.<br>* Other names: Adenoscan(adenosine);Drug: regadenoson<br>* Measuring FFR and Coronary Flow Reserve after administration of IV regadenoson 0.4 mg over 10 seconds.<br>* Other names: Lexiscan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in FFR Between IV Adenosine and IV Regadenoson | FFR (as calculated by the ratio of lowest Pd/Pa at maximal hyperemia) was compared between hyperemia achieved with adenosine and with regadenoson | At maximal, steady-state hyperemia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate Changes With Drug | Maximal heart rate documented following the administration of each agent | During drug infusion and until restoration of baseline hemodynamics | 
| Side Effects of Medication Administration | Chest pain, chest discomfort, burning, flushing, headache, nausea, or shortness of breath | During drug infusion and until restoration of baseline hemodynamics | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fractional flow reserve, adenosine, regadenoson