Clinical trial NCT01842035: Heart Rate Response to Regadenoson and Sudden Cardiac Death
Official title: Heart Rate Response to Regadenoson and Sudden Cardiac Death
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Left Ventricular Systolic Dysfunction
Sudden Cardiac Death
Keywords: Implantable cardiac defibrillator
regadenoson
sudden cardiac death
heart rate response
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Astellas Scientific & Medical Affairs, Inc.
First posted: 2013-04-29
Enrollment: 90
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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:

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.

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

Primary outcomes:
measure: Sudden Cardiac Death
timeFrame: Until end of follow-up, median follow-up 40 months
Secondary outcomes:
measure: All-cause Death
timeFrame: Until end of follow-up, median follow-up 40 months
measure: First Appropriate ICD Therapy
timeFrame: Until end of follow-up, median follow-up 40 months
measure: Inappropriate ICD Therapy
timeFrame: Until end of follow-up, median follow-up 40 months
measure: All-cause Death or First Appropriate ICD Therapy
timeFrame: Until end of follow-up, median follow-up 40 months
measure: Sudden Cardiac Death or Appropriate ICD Therapy
timeFrame: Until end of follow-up, median follow-up 40 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Fadi G Hage, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.