CONFIRM-AF: Insertable Cardiac Monitor for Atrial Fibrillation Detection in Heart Failure Patients

Sponsor

University of Rochester (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04818645

Collaborator

Abbott (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with heart failure (HF) represent a large population of patients who are at high risk for complications related to undiagnosed atrial fibrillation (AF). However, currently there are limited modalities for early AF detection and subsequent stroke prevention in this high-risk population. An implantable cardiac monitor (ICM) is inserted subcutaneously and can provide long term arrhythmia information via remote monitoring.

The Confirm-AF trial seeks to accurately define the burden of AF and other arrhythmias in high-risk HF patients using a Confirm Rx ICM.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Heart Failure	Device: Confirm Rx Insertable Cardiac Monitor Other: Conventional Management and monitoring	N/A

Detailed Description

Over 6 million people in the United States suffer from heart failure (HF). By the year 2030 the prevalence of HF is expected to exceed 8 million people. Heart failure accounts for 1 million hospital admissions each year, costing our economy in excess of $30 billion dollars per year. Mortality in patients with HF remains high, and nearly half of all patients diagnosed with HF will die within 5 years. More than half of all patients admitted with HF decompensation have preserved left ventricular systolic function. Patients with HF and mildly reduced or preserved left ventricular systolic function are at high risk for developing atrial fibrillation (AF), the occurrence of which often contributes to HF decompensation and increases morbidity and all-cause mortality. Similarly, patients with AF are at high risk for developing HF due to loss of atrio-ventricular synchrony and rapid uncontrolled ventricular rates. Detection of AF can be challenging and may go undiagnosed in asymptomatic or minimally symptomatic patients through conventional monitoring methods. Patients with HF represent a large population who are at risk for complications related to undiagnosed AF. AF increases the risk of stroke five-fold and the risk of death nearly two-fold. Moreover, strokes related to AF are twice as likely to be fatal or severely disabling compared to strokes due to other causes, such as ischemic small vessel disease or atheromatous large vessel disease. Cardiac implantable electronic devices (CIEDs), can be used for the early detection of AF in asymptomatic or mildly symptomatic patients with HF. However, current guidelines provide an indication for prophylactic implantable cardioverter defibrillator (ICD) only in HF patients with left ventricular ejection fraction (LVEF) ≤ 35%, whereas there are limited data for device-based detection of AF in HF patients with more preserved LVEF.

Implantable cardiac monitors (ICM) are devices that can be injected into the subcutaneous tissue and can provide automatic electrocardiographic recordings of asymptomatic arrhythmias as well as patient triggered electrocardiographic recordings of symptomatic episodes during long term follow-up. Implantable cardiac monitors are be paired with remote monitoring systems, capable of rapid remote review of electrograms. Accordingly, we hypothesize that a management strategy that incorporates ICM implantation in patients with HF and LVEF >35% will result in a significantly higher rate of AF detection leading to arrhythmia related interventions compared to conventional monitoring and follow-up in patients with HF.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects will be randomized in a 2:1 fashion to undergo implant of a Confirm Rx ICM implant with remote monitoring and symptom-triggered mobile app transmissions versus conventional follow-up without an ICM. Randomization will be stratified by the degree of LV dysfunction to ensure balanced enrollment of HF subjects with mild LV dysfunction (LVEF = 36%-49%) and those with preserved LVEF (≥ 50% [i.e. heart failure with preserved ejection fraction - HFpEF]).Subjects will be randomized in a 2:1 fashion to undergo implant of a Confirm Rx ICM implant with remote monitoring and symptom-triggered mobile app transmissions versus conventional follow-up without an ICM. Randomization will be stratified by the degree of LV dysfunction to ensure balanced enrollment of HF subjects with mild LV dysfunction (LVEF = 36%-49%) and those with preserved LVEF (≥ 50% [i.e. heart failure with preserved ejection fraction - HFpEF]).

Masking:

Single (Outcomes Assessor)

Masking Description:

Events Review Committee: A blinded three-member Events Review Committee will review de-identified source documents obtained from each of the enrolling sites that will only be labelled with a subject ID. No data will be provided indicating the randomized treatment arm to the study and appropriately redacted with no ICM data provided. The information will be used to determine the nature of any clinical and adverse events. Available medical records and source documents will be used to determine cause-specific mortality.

Primary Purpose:

Prevention

Official Title:

Confirm Rx Insertable Cardiac Monitor for Primary Atrial Fibrillation Detection in High Risk Heart Failure Patients

Anticipated Study Start Date :

Oct 1, 2021

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Sep 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Confirm Rx insertable cardiac monitor The Confirm RX implantable cardiac monitor (ICM) is an FDA-approved device that can be injected into the subcutaneous tissue and can provide automatic as well as patient triggered electrocardiographic recordings of symptomatic episodes during long term follow-up. This Implantable cardiac monitor is paired with a remote monitoring smartphone application called My Merlin that capable of rapid remote review of electrograms to be utilized in this study for arrhythmia detection. The Confirm Rx ICM is indicated for the monitoring and diagnostic evaluation of patients who experience unexplained symptoms such as: dizziness, palpitations, chest pain, syncope, and shortness of breath, as well as patients who are at risk for cardiac arrhythmias. It is also indicated for patients who have been previously diagnosed with atrial fibrillation or who are susceptible to developing atrial fibrillation.	Device: Confirm Rx Insertable Cardiac Monitor Subjects will be subcutaneously implanted with an Abbott Confirm Rx ICM with the device implant procedure per standard of care and current labelling. Data related to subjects' arrhythmias, via the Merlin.net Patient CareNetwork will be transmitted on a monthly basis to the treating physician and subsequently to the study coordination and database center (CDC) at the University of Rochester. Data on the frequency/types of symptomatic (patient triggered) versus ICM detected (asymptomatic) arrhythmic events will be collected and adjudicated. Clinical data on medication, device interventions, cardiovascular events will be collected at follow-up visits.
Active Comparator: Conventional Management The conventional management arm will use arrhythmia signs and symptoms to determine occurrence of arrhythmias.	Other: Conventional Management and monitoring Subjects randomized to the conventional management arm of the trial will undergo arrhythmia monitoring based on clinical indications and per standard available modalities including periodic electrocardiograms (ECG), Holter and/or event monitoring.

Arm

Intervention/Treatment

Experimental: Confirm Rx insertable cardiac monitor

The Confirm RX implantable cardiac monitor (ICM) is an FDA-approved device that can be injected into the subcutaneous tissue and can provide automatic as well as patient triggered electrocardiographic recordings of symptomatic episodes during long term follow-up. This Implantable cardiac monitor is paired with a remote monitoring smartphone application called My Merlin that capable of rapid remote review of electrograms to be utilized in this study for arrhythmia detection. The Confirm Rx ICM is indicated for the monitoring and diagnostic evaluation of patients who experience unexplained symptoms such as: dizziness, palpitations, chest pain, syncope, and shortness of breath, as well as patients who are at risk for cardiac arrhythmias. It is also indicated for patients who have been previously diagnosed with atrial fibrillation or who are susceptible to developing atrial fibrillation.

Device: Confirm Rx Insertable Cardiac Monitor

Subjects will be subcutaneously implanted with an Abbott Confirm Rx ICM with the device implant procedure per standard of care and current labelling. Data related to subjects' arrhythmias, via the Merlin.net Patient CareNetwork will be transmitted on a monthly basis to the treating physician and subsequently to the study coordination and database center (CDC) at the University of Rochester. Data on the frequency/types of symptomatic (patient triggered) versus ICM detected (asymptomatic) arrhythmic events will be collected and adjudicated. Clinical data on medication, device interventions, cardiovascular events will be collected at follow-up visits.

Active Comparator: Conventional Management

The conventional management arm will use arrhythmia signs and symptoms to determine occurrence of arrhythmias.

Other: Conventional Management and monitoring

Subjects randomized to the conventional management arm of the trial will undergo arrhythmia monitoring based on clinical indications and per standard available modalities including periodic electrocardiograms (ECG), Holter and/or event monitoring.

Outcome Measures

Primary Outcome Measures

Median Time to first detection of AF lasting > 5 minutes [24 months]
Defined as ICM detected AF in the intervention (implantable cardiac monitor) arm or captured by clinical symptoms and documented by ECG or Holter in the conventional arm.

Secondary Outcome Measures

Time to initiation of guideline directed arrhythmic and HF interventions [24 months]
Interventions such AF ablation, initiation of antiarrhythmic, anticoagulation, beta-blocker therapy and others.
Number cardiovascular hospitalizations or death [24 months]
Total number of cardiovascular hospitalizations or death in each arm.
Mean quality of life measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) [24 months]
All KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent.
Mean percentage of time spent in atrial fibrillation (AF Burden) [24 months]
AF burden, defined as average percentage of time spent in AF (i.e. amount of time spent in AF divided by the total amount of time a patient was monitored). AF burden will be quantified only in the intervention arm.
Time to detection of composite of arrhythmic events endpoint [24 months]
Arrhythmic events consisting of AF, sustained ventricular tachycardia, and high-risk bradyarrhythmias (high degree AV block or sinus pause > 5 seconds), whichever occurs first.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female patients more than 18 years of age (no upper age limit)
HF exacerbation requiring treatment with intravenous decongestive therapy in a hospital setting for an acute HF event during the past 12 calendar months.
LVEF > 35% on a cardiac imaging study (echocardiogram, nuclear imaging, cardiac magnetic resonance imaging) performed during the past 12 calendar months.
Shortness of breath associated with New York Heart Association (NYHA) functional class II, II, or ambulatory class IV.
Willing to undergo an Abbott ICM implant and agree to remote ICM monitoring.

Exclusion Criteria:

Existing implantable cardioverter defibrillator (ICD), biventricular ICD, implantable cardiac monitor or pacemaker.
Known or documented history AF or atrial flutter any time in past.
Class I indication for primary or secondary prevention ICD
Documented ST elevation myocardial infarction in the past 1calendar month.
Life expectancy less than 1 year
Unwilling or unable to cooperate with the protocol
Participation in other clinical trials (observational registries are allowed with approval from the CDC).