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Heart Rate Response to Regadenoson and Sudden Cardiac Death

Primary Purpose

Left Ventricular Systolic Dysfunction, Sudden Cardiac Death

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
regadenoson
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Left Ventricular Systolic Dysfunction focused on measuring Implantable cardiac defibrillator, regadenoson, sudden cardiac death, heart rate response

Eligibility Criteria

19 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Age 19-80 years
  • Female subjects must be (a) at least one year post-menopause or surgically sterile or (b) be non-pregnant and (c) non-lactating.
  • Subject must be able and willing to provide written informed consent

  • Subject must be referred for a clinically indicated ICD and fall into one of the following groups:

    • subjects with left ventricular ejection fraction less than 35% due to prior myocardial infarction who are at least 40 days post-myocardial infarction and are in NYHA functional Class II or III.
    • subjects with non-ischemic dilated cardiomyopathy who have a left ventricular ejection fraction less than or equal to 35% and who are in NYHA functional Class II or III.
    • Subjects with left ventricular dysfunction due to prior myocardial infarction who are at least 40 days post-myocardial infarction, have a left ventricular ejection fraction less than 30%, and are in NYHA functional Class I.

Exclusion Criteria:

  • Female subject who is pregnant or lactating
  • Subject with active severe asthma or chronic obstructive pulmonary disease which, in the Investigator's opinion, places the subject at risk for severe bronchoconstriction
  • Treatment with dipyridamole, theophylline, aminophylline or pentoxifylline within 24 hours of receiving regadenoson
  • Treatment with any investigational drug within 30 days or 5 half lives - whichever is longer prior to study entry
  • Subject with any prior allergic response to aminophylline or other contraindication to receiving intravenous regadenoson
  • Subjects with second or third degree atrioventricular block or dependent on pacemaker
  • Subject with uncontrolled severe hypertension (systolic > 200 mmHg or diastolic >120 mmHg) or pretreatment hypotension (systolic BP <90 mmHg)
  • Subject with hemodynamically significant aortic stenosis or outflow tract obstruction
  • Subject with decompensated heart failure (NYHA functional class IV)
  • Subject with acute myocardial infarction, new onset of ischemia, percutaneous coronary intervention, or coronary artery bypass grafting within 30 days of receiving regadenoson
  • Subject is on dialysis for end stage renal disease or has an estimated glomerular filtration rate < 15 mL/min
  • Subjects with cardiac transplantation

Sites / Locations

  • UAB

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Regadenoson

Arm Description

Prior to the implantation of a clinically indicated ICD, the heart rate response to regadenoson will be assessed. Regadenoson will be administered intravenously as a fixed intravenous bolus dose of 400 μg followed by a 5 mL saline flush. Medications (including beta-blockers) will be withheld on the morning of the test. The heart rate and blood pressure will be measured at baseline and every minute after regadenoson bolus for at least 5 minutes and until the heart rate and blood pressure are clearly returning towards baseline. --------------------------------------------------------------------------------

Outcomes

Primary Outcome Measures

Sudden Cardiac Death
Sudden cardiac death will be defined as death within 1 hour of symptom onset, or an unobserved death in which the patient was seen and known to be doing well within 24 hours of death. Survivors of aborted sudden cardiac death, resuscitated cardiac arrest, and those receiving appropriate ICD therapy will also be considered to have experienced sudden cardiac death and will be included in the primary end point.

Secondary Outcome Measures

All-cause Death
death from any cause
First Appropriate ICD Therapy
antitachycardia pacing therapy or shock for tachyarrhythmia determined by evaluation of the clinical information and by device diagnostics to be either ventricular fibrillation or ventricular tachycardia
Inappropriate ICD Therapy
unnecessary antitachycardia pacing or shock delivered by the ICD for a rhythm that is not a true ventricular fibrillation or ventricular tachycardia
All-cause Death or First Appropriate ICD Therapy
death or antitachycardia pacing therapy or shock for tachyarrhythmia determined by evaluation of the clinical information and by device diagnostics to be either ventricular fibrillation or ventricular tachycardia
Sudden Cardiac Death or Appropriate ICD Therapy
Sudden cardiac death or antitachycardia pacing therapy or shock for tachyarrhythmia determined by evaluation of the clinical information and by device diagnostics to be either ventricular fibrillation or ventricular tachycardia

Full Information

First Posted
March 13, 2013
Last Updated
October 12, 2022
Sponsor
University of Alabama at Birmingham
Collaborators
Astellas Scientific & Medical Affairs, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01842035
Brief Title
Heart Rate Response to Regadenoson and Sudden Cardiac Death
Official Title
Heart Rate Response to Regadenoson and Sudden Cardiac Death
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
February 2013 (Actual)
Primary Completion Date
April 2020 (Actual)
Study Completion Date
July 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
Collaborators
Astellas Scientific & Medical Affairs, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine whether a blunted heart rate response to regadenoson is an independent predictor of sudden cardiac death.
Detailed Description
In patients with heart failure and in those with a history of sudden cardiac death, an Implantable Cardiac Defibrillator (ICD) reduces death rates. However, not all patients with an ICD receive appropriate therapy from it. Inappropriate ICD shocks are common and are associated with worse quality of life and increased death rate. We hope to establish a better predictor of risk of sudden cardiac death and of response to ICD. We are conducting a prospective observational study of 150 patients (18-80 years) with an indication for ICD implantation for primary prevention of sudden cardiac death. Prior to the implantation of a clinically indicated ICD, the heart rate response to regadenoson will be assessed. Regadenoson will be administered intravenously as a fixed intravenous bolus dose of 400 μg followed by a 5 mL saline flush. The main objectives of this proposal are to investigate whether: A blunted heart rate response to regadenoson is an independent predictor of sudden cardiac death. A blunted heart rate response to regadenoson can be used as a predictor of response to ICD on top of traditionally used indicators. We Hypothesize that: Patients with a blunted heart rate response to regadenoson are at higher risk of sudden cardiac death (death or appropriate cardiac defibrillation). This risk is maintained after controlling for age, gender, left ventricular ejection fraction, heart failure symptoms and medication use. Patients with a normal heart rate response to regadenoson have a low rate of events (death or appropriate cardiac defibrillation) despite meeting current indications for having an ICD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Left Ventricular Systolic Dysfunction, Sudden Cardiac Death
Keywords
Implantable cardiac defibrillator, regadenoson, sudden cardiac death, heart rate response

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Regadenoson
Arm Type
Experimental
Arm Description
Prior to the implantation of a clinically indicated ICD, the heart rate response to regadenoson will be assessed. Regadenoson will be administered intravenously as a fixed intravenous bolus dose of 400 μg followed by a 5 mL saline flush. Medications (including beta-blockers) will be withheld on the morning of the test. The heart rate and blood pressure will be measured at baseline and every minute after regadenoson bolus for at least 5 minutes and until the heart rate and blood pressure are clearly returning towards baseline. --------------------------------------------------------------------------------
Intervention Type
Drug
Intervention Name(s)
regadenoson
Other Intervention Name(s)
Lexiscan
Intervention Description
Prior to the implantation of a clinically indicated ICD, the heart rate response to regadenoson will be assessed. Regadenoson will be administered intravenously as a fixed intravenous bolus dose of 400 μg followed by a 5 mL saline flush. Medications (including beta-blockers) will be withheld on the morning of the test. The heart rate and blood pressure will be measured at baseline and every minute after regadenoson bolus for at least 5 minutes and until the heart rate and blood pressure are clearly returning towards baseline.
Primary Outcome Measure Information:
Title
Sudden Cardiac Death
Description
Sudden cardiac death will be defined as death within 1 hour of symptom onset, or an unobserved death in which the patient was seen and known to be doing well within 24 hours of death. Survivors of aborted sudden cardiac death, resuscitated cardiac arrest, and those receiving appropriate ICD therapy will also be considered to have experienced sudden cardiac death and will be included in the primary end point.
Time Frame
Until end of follow-up, median follow-up 40 months
Secondary Outcome Measure Information:
Title
All-cause Death
Description
death from any cause
Time Frame
Until end of follow-up, median follow-up 40 months
Title
First Appropriate ICD Therapy
Description
antitachycardia pacing therapy or shock for tachyarrhythmia determined by evaluation of the clinical information and by device diagnostics to be either ventricular fibrillation or ventricular tachycardia
Time Frame
Until end of follow-up, median follow-up 40 months
Title
Inappropriate ICD Therapy
Description
unnecessary antitachycardia pacing or shock delivered by the ICD for a rhythm that is not a true ventricular fibrillation or ventricular tachycardia
Time Frame
Until end of follow-up, median follow-up 40 months
Title
All-cause Death or First Appropriate ICD Therapy
Description
death or antitachycardia pacing therapy or shock for tachyarrhythmia determined by evaluation of the clinical information and by device diagnostics to be either ventricular fibrillation or ventricular tachycardia
Time Frame
Until end of follow-up, median follow-up 40 months
Title
Sudden Cardiac Death or Appropriate ICD Therapy
Description
Sudden cardiac death or antitachycardia pacing therapy or shock for tachyarrhythmia determined by evaluation of the clinical information and by device diagnostics to be either ventricular fibrillation or ventricular tachycardia
Time Frame
Until end of follow-up, median follow-up 40 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Age 19-80 years Female subjects must be (a) at least one year post-menopause or surgically sterile or (b) be non-pregnant and (c) non-lactating. Subject must be able and willing to provide written informed consent Subject must be referred for a clinically indicated ICD and fall into one of the following groups: subjects with left ventricular ejection fraction less than 35% due to prior myocardial infarction who are at least 40 days post-myocardial infarction and are in NYHA functional Class II or III. subjects with non-ischemic dilated cardiomyopathy who have a left ventricular ejection fraction less than or equal to 35% and who are in NYHA functional Class II or III. Subjects with left ventricular dysfunction due to prior myocardial infarction who are at least 40 days post-myocardial infarction, have a left ventricular ejection fraction less than 30%, and are in NYHA functional Class I. Exclusion Criteria: Female subject who is pregnant or lactating Subject with active severe asthma or chronic obstructive pulmonary disease which, in the Investigator's opinion, places the subject at risk for severe bronchoconstriction Treatment with dipyridamole, theophylline, aminophylline or pentoxifylline within 24 hours of receiving regadenoson Treatment with any investigational drug within 30 days or 5 half lives - whichever is longer prior to study entry Subject with any prior allergic response to aminophylline or other contraindication to receiving intravenous regadenoson Subjects with second or third degree atrioventricular block or dependent on pacemaker Subject with uncontrolled severe hypertension (systolic > 200 mmHg or diastolic >120 mmHg) or pretreatment hypotension (systolic BP <90 mmHg) Subject with hemodynamically significant aortic stenosis or outflow tract obstruction Subject with decompensated heart failure (NYHA functional class IV) Subject with acute myocardial infarction, new onset of ischemia, percutaneous coronary intervention, or coronary artery bypass grafting within 30 days of receiving regadenoson Subject is on dialysis for end stage renal disease or has an estimated glomerular filtration rate < 15 mL/min Subjects with cardiac transplantation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fadi G Hage, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
UAB
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19332209
Citation
Hage FG, Heo J, Franks B, Belardinelli L, Blackburn B, Wang W, Iskandrian AE. Differences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus. Am Heart J. 2009 Apr;157(4):771-6. doi: 10.1016/j.ahj.2009.01.011. Epub 2009 Mar 6.
Results Reference
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PubMed Identifier
20211328
Citation
Hage FG, Perry G, Heo J, Iskandrian AE. Blunting of the heart rate response to adenosine and regadenoson in relation to hyperglycemia and the metabolic syndrome. Am J Cardiol. 2010 Mar 15;105(6):839-43. doi: 10.1016/j.amjcard.2009.11.042.
Results Reference
background
PubMed Identifier
21835298
Citation
Hage FG, Dean P, Bhatia V, Iqbal F, Heo J, Iskandrian AE. The prognostic value of the heart rate response to adenosine in relation to diabetes mellitus and chronic kidney disease. Am Heart J. 2011 Aug;162(2):356-62. doi: 10.1016/j.ahj.2011.05.014. Epub 2011 Jul 18.
Results Reference
background
PubMed Identifier
21785922
Citation
Hage FG, Dean P, Iqbal F, Heo J, Iskandrian AE. A blunted heart rate response to regadenoson is an independent prognostic indicator in patients undergoing myocardial perfusion imaging. J Nucl Cardiol. 2011 Dec;18(6):1086-94. doi: 10.1007/s12350-011-9429-1. Epub 2011 Jul 22.
Results Reference
background
PubMed Identifier
23111139
Citation
Iqbal FM, Al Jaroudi W, Sanam K, Sweeney A, Heo J, Iskandrian AE, Hage FG. Reclassification of cardiovascular risk in patients with normal myocardial perfusion imaging using heart rate response to vasodilator stress. Am J Cardiol. 2013 Jan 15;111(2):190-5. doi: 10.1016/j.amjcard.2012.09.013. Epub 2012 Oct 27.
Results Reference
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Heart Rate Response to Regadenoson and Sudden Cardiac Death

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