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

• Sponsor: St. Louis University
• Collaborators: University of Florida; Astellas Pharma US, Inc.
• Information provided by (Responsible Party): Michael J. Lim, St. Louis University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: adenosine; Drug: regadenoson	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Utilization of Lexiscan (Regadenoson)in the Cardiac Catheterization Lab to Achieve Maximal Hyperemia for Coronary Physiologic Assessment With Fractional Flow Reserve
• Study Start Date: July 2010
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: April 2013

Arms and Interventions

Arm

Intervention/treatment

Experimental: Adenosine then Regadenoson; 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; Measuring FFR and Coronary Flow Reserve after administration of IV adenosine 140 mcg/kg/min for 2 minutes.; Other Name: Adenoscan(adenosine); Drug: regadenoson; Measuring FFR and Coronary Flow Reserve after administration of IV regadenoson 0.4 mg over 10 seconds.; Other Name: Lexiscan

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Heart Rate Changes With Drug [ Time Frame: During drug infusion and until restoration of baseline hemodynamics ]
   Maximal heart rate documented following the administration of each agent
2. Side Effects of Medication Administration [ Time Frame: During drug infusion and until restoration of baseline hemodynamics ]
   Chest pain, chest discomfort, burning, flushing, headache, nausea, or shortness of breath

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Florida

University of Florida

Jacksonville, Florida, United States, 32209

United States, Missouri

St. Louis University

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

St. Louis University

University of Florida

Astellas Pharma US, Inc.

Investigators

• Principal Investigator: Michael J Lim, MD; St. Louis University

More Information

Publications:

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.

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.

Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrøm 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.

Lim MJ, Kern MJ. Coronary pathophysiology in the cardiac catheterization laboratory. Curr Probl Cardiol. 2006 Aug;31(8):493-550. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Michael J. Lim, Director, Division of Cardiology, St. Louis University
• ClinicalTrials.gov Identifier: NCT01161121 History of Changes
• Other Study ID Numbers: Rega-9I06
• First Posted: July 13, 2010
• Results First Posted: June 19, 2017
• Last Update Posted: June 23, 2017
• Last Verified: June 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Michael J. Lim, St. Louis University:

Fractional flow reserve; adenosine; regadenoson

Additional relevant MeSH terms:

Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Hyperemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Adenosine; Regadenoson; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Vasodilator Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adenosine A2 Receptor Agonists