Coronary Artery Disease
Conditions
Keywords
Fractional flow reserve, adenosine, regadenoson
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.
Interventions
DRUGadenosine
Measuring FFR and Coronary Flow Reserve after administration of IV adenosine 140 mcg/kg/min for 2 minutes.
DRUGregadenoson
Measuring FFR and Coronary Flow Reserve after administration of IV regadenoson 0.4 mg over 10 seconds.
Sponsors
University of Florida
Astellas Pharma US, Inc.
St. Louis University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in FFR Between IV Adenosine and IV Regadenoson | 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
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate Changes With Drug | During drug infusion and until restoration of baseline hemodynamics | Maximal heart rate documented following the administration of each agent |
| Side Effects of Medication Administration | During drug infusion and until restoration of baseline hemodynamics | Chest pain, chest discomfort, burning, flushing, headache, nausea, or shortness of breath |
Countries
United States
Participant flow
Recruitment details
Patients provided written consent for participation in the study prior to cardiac catheterization. Diagnostic coronary angiography was performed utilizing standard techniques. Patients in whom the operator believed needed physiologic coronary assessment with Fractional Flow Reserve (FFR) were then eligible for participation in the study.
Participants by arm
| Arm | Count |
|---|---|
| Adenosine, Regadenoson Each patient underwent standard intravenous adenosine infusion (140mcg/kg/min) with invasive pressure recordings for 2 min, or until maximal hyperemia occurred. Five minutes after return to baseline hemodynamics, a single intravenous bolus of 0.4 mg regadenoson was administered, and pressures were recorded for 5 min. FFR values were compared by linear regression and Bland-Altman analysis. | 46 |
| Total | 46 |
Baseline characteristics
| Characteristic | Adenosine, Regadenoson |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Age, Continuous | 59 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 46 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 46 | 28 / 46 |
| serious Total, serious adverse events | 0 / 46 | 0 / 46 |
Outcome results
Primary
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
Time frame: At maximal, steady-state hyperemia
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adenosine | Difference in FFR Between IV Adenosine and IV Regadenoson | 0.84 ratio (Pd/Pa) | Standard Deviation 0.11 |
| Regadenoson | Difference in FFR Between IV Adenosine and IV Regadenoson | 0.84 ratio (Pd/Pa) | Standard Deviation 0.1 |
Secondary
Heart Rate Changes With Drug
Maximal heart rate documented following the administration of each agent
Time frame: During drug infusion and until restoration of baseline hemodynamics
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adenosine | Heart Rate Changes With Drug | Baseline Heart Rate | 70.8 beats per minute | Standard Deviation 11.5 |
| Adenosine | Heart Rate Changes With Drug | Maximal Heart Rate | 81.7 beats per minute | Standard Deviation 13.4 |
| Regadenoson | Heart Rate Changes With Drug | Baseline Heart Rate | 72.4 beats per minute | Standard Deviation 12 |
| Regadenoson | Heart Rate Changes With Drug | Maximal Heart Rate | 90.4 beats per minute | Standard Deviation 13 |
Secondary
Side Effects of Medication Administration
Chest pain, chest discomfort, burning, flushing, headache, nausea, or shortness of breath
Time frame: During drug infusion and until restoration of baseline hemodynamics
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adenosine | Side Effects of Medication Administration | Dyspnea | 14 participants |
| Adenosine | Side Effects of Medication Administration | Chest Pain | 16 participants |
| Adenosine | Side Effects of Medication Administration | Any Symptom | 27 participants |
| Regadenoson | Side Effects of Medication Administration | Dyspnea | 13 participants |
| Regadenoson | Side Effects of Medication Administration | Chest Pain | 13 participants |
| Regadenoson | Side Effects of Medication Administration | Any Symptom | 28 participants |