Subclinical AtrIal FibrilLation and StrokE PreveNtion Trial (SILENT)

SILENT - Subclinical AtrIal FibrilLation and StrokE PreveNtion Trial

Introduction: Patients with atrial fibrillation (AF) have a substantial risk of stroke and systemic embolism. Subclinical AF is often suspected to be the cause of stroke in these patients. The detection of asymptomatic AF episodes is a challenge and the real rate of occurrence of these episodes remains unknown. The rate of stroke is high among patients who have received a pacemaker and this device can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented AF. The net benefit of anticoagulant treatment is well established in patients with clinical AF but data about anticoagulation in subclinical AF setting is unknown. The aim of this study is to assess the impact of anticoagulant therapy on subclinical AF, directed by cardiac implantable electronic device (CIED) intensive monitoring, on the incidence of stroke and systemic embolism and correlate the AF episodes detected by CIED with thromboembolic events. Methods: This is a prospective, randomized, unicentric, parallel clinical study in patients with atrioventricular pacemaker, defibrillator, or cardiac resynchronization therapy devices in sinus rhythm and CHADS2 score (an index of the risk of stroke in patients with atrial fibrillation, range from 0 to 6) ≥ 2 . Patients will be randomized to the intervention group - intensive monitoring arm (Group I) or control group - routine schedule arm (Group II) in a 1:1 ratio. Time to inclusion will be 24 months and all patients will be followed up for a period of 36 months. Group I, patients will be submitted to device data collection every 2 months, while in Group II, patients will be managed conventionally. Patients from Group I with episodes of subclinical AF will receive anticoagulant therapy, as well as patients with clinical AF of both arms. Device data from Group II patients will not be analyzed until they achieve the primary endpoint. Primary endpoint: stroke or systemic embolism. Secondary endpoints: subclinical AF rate, total mortality, cardiovascular mortality, myocardial infarction, cardiovascular hospitalization, and bleeding rates. Expected outcome: It is expected that anticoagulation therapy of subclinical AF directed by CIED intensive monitoring will reduce the incidence of stroke and systemic embolism comparing to patients with non-diagnosed subclinical AF.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Anticoagulant

Detailed Description

Patients with atrial fibrillation (AF) have a substantial risk of stroke and systemic embolism. Subclinical AF is often suspected to be the cause of stroke in these patients. The detection of asymptomatic AF episodes is a challenge and the real rate of occurrence of these episodes remains unknown. The rate of stroke is high among patients who have received a pacemaker and this device can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented AF. The net benefit of anticoagulant treatment is well established in patients with clinical AF but data about anticoagulation for subclinical AF settings is unknown. The aim of this study is to assess the impact of anticoagulant therapy on subclinical AF, directed by cardiac implantable electronic device (CIED) intensive monitoring, on the incidence of stroke and systemic embolism and correlate the AF episodes detected by CIED with thromboembolic events. Methods: This is a prospective, randomized, unicentric, parallel clinical study in patients with an atrioventricular pacemaker, defibrillator, or cardiac resynchronization therapy devices in sinus rhythm and CHADS2 score (an index of the risk of stroke in patients with atrial fibrillation, range from 0 to 6) ≥ 2 . Patients will be randomized to the intervention group - intensive monitoring arm (Group I) or control group - routine schedule arm (Group II) in a 1:1 ratio. Time to inclusion will be 24 months and all patients will be followed up for a period of 36 months. Group I, patients will be submitted to device data collection every 2 months, while in Group II, patients will be managed conventionally. Patients from Group I with episodes of subclinical AF will receive anticoagulant therapy, as well as patients with clinical AF of both arms. Device data from Group II patients will not be analyzed until they achieve the primary endpoint. Primary endpoint: stroke or systemic embolism. Secondary endpoints: subclinical AF rate, total mortality, cardiovascular mortality, myocardial infarction, cardiovascular hospitalization, and bleeding rates. Expected outcome: It is expected that anticoagulation therapy of subclinical AF directed by CIED intensive monitoring will reduce the incidence of stroke and systemic embolism comparing to patients with non-diagnosed subclinical AF.

• Study Type: Interventional
• Enrollment (Anticipated): 2054
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Martino Martinelli Filho, PhD, MD; Phone Number: +551126615515; Email: martino@incor.usp.br
• Study Contact Backup: Name: Sergio F Siqueira, Eng; Phone Number: +5511973083052; Email: siqueira@incor.usp.br

Study Locations

• Brazil
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-900
      • Recruiting
      • Martino Martinelli Filho
      • Contact: Sergio F Siqueira, Eng; Phone Number: +5511973083052; Email: siqueira@incor.usp.br
      • Contact: Martino MM Martinelli Filho, PHD; Phone Number: 5517 55 11 2661 5517; Email: martino.filho@incor.usp.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >= 18 years
• CHADS2 score >=2
• Sinus rhythm
• Cardiac Implantable Electronic Device

Exclusion Criteria:

• Atrial fibrillation
• Severe heart valve disease
• Anticoagulation therapy
• Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: anticoagulant; Prescription of oral anticoagulation for patients with silent AF (detected by the pacemaker).	Drug: Anticoagulant; Anticoagulant treatment will be started in case of subclinical atrial fibrillation (>5,5 hours per day) be diagnosed by cardiac implantable electronic device at intervention group, or clinical atrial fibrillation in both groups.; Other Names: Oral Anticoagulant
No Intervention: Control; Patients with silent FA detected only by the pacemaker will no receive oral anticoagulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke	Occurrence of stroke	36 months
Systemic embolism	Occurrence of systemic embolism	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subclinical AF rate	Rate subclinical AF documentation by pacemaker	36 months
Total mortality	All cause mortality	36 months
Cardiovascular mortality	Adjudicated cardiovascular mortality	36 months
Myocardial infarction	Occurrence of myocardial infarction	36 months
Cardiovascular hospitalization	Adjudicated cardiovascular hospitalization	36 months
Bleeding rates	Occurrence of bleeding	36 months

Collaborators and Investigators

• Sponsor: InCor Heart Institute
• Investigators: Study Director: Sergio F Siqueira, Eng, Biomedical Eng

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2015
• Primary Completion (Anticipated): October 31, 2025
• Study Completion (Anticipated): October 31, 2025

Study Registration Dates

• First Submitted: September 24, 2013
• First Submitted That Met QC Criteria: December 3, 2013
• First Posted (Estimate): December 9, 2013

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 27, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: stroke; atrial fibrillation; anticoagulant; pacemaker
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Anticoagulants
• Other Study ID Numbers: SILENT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No