Reveal Chagas: Clinical Evidence of the Implantable Cardiac Monitor in Patients With Chagas Disease

Study Overview
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Brief Summary
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The study Reveal Chagas: Clinical Evidence of the Implantable Cardiac Monitor in Patients with Chagas Disease is a prospective, multicenter, randomized study that is being conducted at several centers in Latin America with commercially available products. The primary study hypothesis is that patients with implantable cardiac monitors will have a shorter time to the decision to treat for electrical or arrhythmic disorders during the follow-up period. The geography includes Argentina and Colombia.

Detailed Description
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The purpose is to study the possible benefit of a superior treatment decision rate for cardiac arrhythmias (brady- and or/ tachyarrhythmias) using an implantable cardiac monitor (ICM) in patients with Chagas Disease diagnosed by serology, who are asymptomatic and/or minimally symptomatic. Patients that meet inclusion criteria of the study will be randomized to standard care or standard care plus ICM. Approximately half of the patients will receive an ICM. All patients will be followed for 36 months. It is expected that the enrollment phase will last 1 year, and that the total study duration will be 4 years. The study is expected to end in 2017. One hundred and two patients are needed for 95% confidence level and 80% statistical power to be randomized into the study, at approximately 5 centers in Latin America. Patients will be considered enrolled once they have signed the Informed Consent. The following additional parameters will also be collected: Recorded arrhythmic events stored within the ICM (bradyarrhythmia and tachyarrhythmia) Time duration spent in arrhythmia and incidence of symptomatic arrhythmias in patients with an ICM. Clinical data on subject outcomes and changes in heart failure as assessed by heart failure hospitalizations, New York Heart Association class and mortality.

Official Title
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Reveal Chagas: Clinical Evidence of the Implantable Cardiac Monitor in Patients With Chagas Disease

Conditions
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Chagas Disease, Heart Diseases

Intervention / Treatment
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* Device: Implantable Cardiac Monitor
* Procedure: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have Chagas disease, confirmed by two serological tests. Provide evidence through any of the following diagnosis methods: Rest ECG, 24 hour Holter monitoring, electrophysiological study, stress test or loop monitoring, at least one electrical disorder consistent with sinus bradycardia greater than 45 and lower than 60 bpm, sinus arrest not greater than 2.0 seconds, second degree atrial sinus block, intraventricular conduction disorders such as right branch, left branch or a bifascicular blockage type, first degree A-V blockage, or of type I second degree AV Block without associated bradycardia, atrial and/or ventricular arrhythmias that do NOT constitute an indication for pacemaker implant, ICD or mapping and radio frequency ablation. Be asymptomatic or having minimal isolated unspecific symptoms not consistent with cardiac arrest, aborted sudden death, syncope, frequent and recurrent palpitations, cardiac failure, and lower extremity edema. Have ejection fraction of left ventricle >35% Be able to give his/her written informed consent. Subject should be > 21 years old. Be able to return for follow-up visits as required. Exclusion Criteria: Class I or II (according to AHA/HRS/ESC guidelines) indication for final implantation of pacemaker, ICD, or cardiac resynchronizer. Exhibit extrinsic causes of sinus dysfunction or A-V blockage. Exhibit infiltrative myocardial diseases such as tumors or associated valvular defects. Suffer any concurrent disease that may limit the follow up or evaluation. Suffer aftereffects of cerebral embolism. Suffer ablation or isolation of pulmonary veins previous to their inclusion in the study. Not being able or willing to comply with the follow-up schedule. Have previous lesions of the spinal cord or aftereffects of skull trauma. Have a record of epilepsy. Receive pharmacological treatment for other diseases that may modify the autonomic function. Have a record of myocardial infarction. History of alcohol abuse or drug addiction. History of emotional instability, unstable psychiatric disorders or are under treatment for such disorders. Have previously implanted pacemakers, cardiodefibrillators or CRT systems. Are included or intend to participate in another study of devices during the course of this study. Have a clinical condition that may limit life expectancy to < 36 months. Use of Antiarrhythmic drugs, except Beta Blockers

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reveal XT plus SOC<br>Standard of care treatment plus the Reveal XT Implantable Cardiac Monitor. Treatment will follow the same schedule of the standard of care arm regarding exam, ECG and Holter every 6 months, and an Echo, Chest X-Ray and Stress test every 12 months. The addition will be device interrogation at every 6 month exam. Participation will last 36 months. | Device: Implantable Cardiac Monitor<br>* 9529 Reveal XT Implantable Cardiac Monitor as well as the use of 9539 Reveal XT Patient Assistant.<br>* Other names: 9539 Reveal XT Patient Assistant;|
| Active Comparator: Standard of Care<br>Standard of care arm as described by exam, ECG and Holter every 6 months, and an Echo, Chest X-Ray and Stress test every 12 months. Participation will last 36 months. | Procedure: Standard of Care<br>* Standard of care arm including exam, ECG and Holter every 6 months, and an Echo, Chest X-Ray and Stress test every 12 months.<br>* Other names: SOC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the time to the physician's decision to treat for electrical disorders (brady/tachyarrhythmias) between the two randomized groups. | The primary endpoint is time to the first decision to implant a device (IPG, CRT-P, ICD or CRT-D) or prescribe anti-arrhythmic drugs. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summarize the recorded arrhythmic events stored within the ICM (bradyarrhythmia and tachyarrhythmia. | Compute summary statistics for arrhythmic events recorded during follow-up, whether or not related to symptoms, for all patients in the ICM arm, including the total number, distribution (e.g., minimum, maximum, median, quartiles, and standard deviation), number per patient year, number of patients having events and percentage of patients having events. Summary statistics for bradyarrhythmia and tachyarrhythmia events will also be computed separately. | 36 months | 
| Compute the time duration spent in arrhythmias for ICM patients. | Compute the total duration each ICM patient spends in, 1) atrial arrhythmias and 2) ventricular arrhythmias during the entire follow-up period, and their corresponding distribution (e.g., minimum, maximum, median, quartiles, standard deviation). Compute the average duration each patient spends in an, 1) atrial arrhythmia event, and 2) a ventricular arrhythmia event, and the corresponding distributions. | 36 months | 
| Compute the incidence of symptomatic arrhythmias in patients with an ICM | Compute the incidence rate of symptomatic arrhythmias in patients with an ICM, overall, and for bradyarrhythmias and tachyarrhythmias separately. | 36 months | 
| Compare the time to the physician's decision to treat with components of the composite primary endpoint between randomization arms. | Individually compare the time to the physicians' decision to treat with the following between the two randomization arms: A device of any type (IPG, CRT-P, ICD or CRT-D) A pacemaker (IPG) Anti-arrhythmic drug therapy A defibrillator (ICD or CRT-D) or prescribe anti-arrhythmic drug therapy | 36 months | 
| Compare the mortality rate between randomization arms. | Compare the mortality rate between randomization arms. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chagas Disease, Chagasic, Reveal XT, Implantable Cardiac Monitor, ICM