Heart Rate Response to Regadenoson and Sudden Cardiac Death

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01842035

Enrollment

Registered

2013-04-29

Start date

2013-02-28

Completion date

2022-07-31

Last updated

2022-10-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Left Ventricular Systolic Dysfunction, Sudden Cardiac Death

Keywords

Implantable cardiac defibrillator, regadenoson, sudden cardiac death, heart rate response

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.

Interventions

DRUGregadenoson

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

DIAGNOSTIC

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

19 Years to 80 Years

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

Design outcomes

Primary

Measure	Time frame	Description
Sudden Cardiac Death	Until end of follow-up, median follow-up 40 months	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

Measure	Time frame	Description
All-cause Death	Until end of follow-up, median follow-up 40 months	death from any cause
First Appropriate ICD Therapy	Until end of follow-up, median follow-up 40 months	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	Until end of follow-up, median follow-up 40 months	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	Until end of follow-up, median follow-up 40 months	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	Until end of follow-up, median follow-up 40 months	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

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. \-------------------------------------------------------------------------------- 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.	90
Total	90

Arm

Count

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. \-------------------------------------------------------------------------------- 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.

Total

Baseline characteristics

Characteristic	Regadenoson
Age, Continuous	60 years STANDARD_DEVIATION 14
Race/Ethnicity, Customized Black	36 Participants
Race/Ethnicity, Customized White	54 Participants
Region of Enrollment United States	90 participants
Sex: Female, Male Female	36 Participants
Sex: Female, Male Male	54 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	16 / 90
other Total, other adverse events	24 / 90
serious Total, serious adverse events	0 / 90

Outcome results

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.