Heart Rate Response to Regadenoson and Sudden Cardiac Death

Sudden Cardiac Death Clinical Trial

Official title:

Heart Rate Response to Regadenoson and Sudden Cardiac Death

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01842035
• Other study ID #: REGA 12D05
• Status: Completed
• Phase: N/A
• Start date: February 2013
• Est. completion date: July 2022

Study information

• Verified date: October 2022
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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: 1. A blunted heart rate response to regadenoson is an independent predictor of sudden cardiac death. 2. 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: 1. 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. 2. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: July 2022
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Death
• Death, Sudden, Cardiac
• Left Ventricular Systolic Dysfunction
• Sudden Cardiac Death

Intervention

Drug:
• regadenoson
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.

Locations

Country	Name	City	State
United States	UAB	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Astellas Scientific & Medical Affairs, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Until end of follow-up, median follow-up 40 months
Secondary	All-cause Death	death from any cause	Until end of follow-up, median follow-up 40 months
Secondary	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	Until end of follow-up, median follow-up 40 months
Secondary	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	Until end of follow-up, median follow-up 40 months
Secondary	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	Until end of follow-up, median follow-up 40 months
Secondary	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	Until end of follow-up, median follow-up 40 months