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| Name | Class |
|---|---|
| University of Florida | OTHER |
| Astellas Pharma US, Inc. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adenosine then Regadenoson | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| adenosine | Drug | Measuring FFR and Coronary Flow Reserve after administration of IV adenosine 140 mcg/kg/min for 2 minutes. |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael J Lim, MD | St. Louis University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida | Jacksonville | Florida | 32209 | United States | ||
| St. Louis University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 7586302 | Background | 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. | |
| 17826318 | Background | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. All patients to receive Adenosine infusion followed by Regadenoson IV bolus upon return of coronary flow velocity to 15% of pre-dose value. Adenosine : Injection of IV Adenosine for 2 minutes at rate of 140mcg/kg to dilate coronary arteries and provoke maximal hyperemia. Regadenoson : Administration of IV regadenoson bolus 0.4 mg/5 mls over 10 seconds followed by a 5 cc NS saline flush |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Patients with intermediate to severe, single vessel or multi-vessel, angiographic coronary artery disease(visual 40%-70% angiographic stenosis) whose lesion assessment with FFR is planned, were eligible for enrollment. A total of up to 50 subjects(25 at University of Florida Health Science Center and 25 at St. Louis University) will be enrolled.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Per protocol | Posted | Mean | Standard Deviation | ratio (Pd/Pa) | At maximal, steady-state hyperemia |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Adenosine | Adenosine infusion will be compared to Regadenoson for 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 : Injection of IV Adenosine for 2 minutes at rate of 140mcg/kg to dilate coronary arteries and provoke maximal hyperemia adenosine : Measuring FFR and Coronary Flow Reserve after administration of IV adenosine 140 mcg/kg/min for 2 minutes. regadenoson : Measuring FFR and Coronary Flow Reserve after administration of IV regadenoson 0.4 mg over 10 seconds. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | CTCAE | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Michael Lim | St. Louis University | 314-268-7992 | limmj@slu.edu |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000241 | Adenosine |
| C430916 | regadenoson |
| ID | Term |
|---|---|
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| regadenoson | Drug | Measuring FFR and Coronary Flow Reserve after administration of IV regadenoson 0.4 mg over 10 seconds. |
|
|
Chest pain, chest discomfort, burning, flushing, headache, nausea, or shortness of breath
| During drug infusion and until restoration of baseline hemodynamics |
| St Louis |
| Missouri |
| 63110 |
| United States |
| 19144937 | Background | 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. |
| 16920478 | Background | 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. |
| 26242981 | Derived | 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. |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| Regadenoson |
Once the mean coronary flow velocity returns to within 15% pre-dose value following IV infusion of Adenosine, Regadenoson IV injection will be given at 0.4 mg 5/ml- 0.08mg/ml over 10 seconds followed by a 5 cc IV saline flush. regadenoson : Measuring FFR and Coronary Flow Reserve after administration of IV regadenoson 0.4 mg over 10 seconds. |
|
|
| Secondary | Heart Rate Changes With Drug | Maximal heart rate documented following the administration of each agent | Posted | Mean | Standard Deviation | beats per minute | During drug infusion and until restoration of baseline hemodynamics |
|
|
|
| Secondary | Side Effects of Medication Administration | Chest pain, chest discomfort, burning, flushing, headache, nausea, or shortness of breath | Posted | Number | participants | During drug infusion and until restoration of baseline hemodynamics |
|
|
|
| 0 |
| 46 |
| 27 |
| 46 |
| EG001 | Regadenoson | Once the mean coronary flow velocity returns to within 15% pre-dose value then Regadenoson IV injection will be given at 0.4 mg 5/ml- 0.08mg/ml. Then, a 5 cc saline flush will be administered. regadenoson : Measuring FFR and Coronary Flow Reserve after administration of IV regadenoson 0.4 mg over 10 seconds. | 0 | 46 | 28 | 46 |
| Flushing | Skin and subcutaneous tissue disorders | CTCAE | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE | Systematic Assessment |
|
| Cardiac General -Chest Pain | Cardiac disorders | CTCAE | Systematic Assessment |
|
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| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| Any Symptom |
|