Ivabradine for Rate Control in Permanent Atrial Fibrillation

Ivabradine may be useful as a rate controlling agent in atrial fibrillation without negative effects on hemodynamics and inotropy. The objective in this proof of concept study is to investigate the hypothesis that ivabradine will slow the ventricular response in patients with permanent atrial fibrillation and previously-implanted pacemakers.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Atrial Fibrillation, Persistent
• Intervention / Treatment: Drug: Ivabradine

Detailed Description

In a simple cross-over study, the investigators will evaluate the impact of oral Ivabradine on exercise treadmill test, percent pacing as stored in pacemaker diagnostics, and 6 minute walk test.

Aim/Hypotheses

• To determine if the addition of Ivabradine to baseline cardiac medications slows mean and maximum heart rates in permanent atrial fibrillation

• Ivabradine will lower mean and maximum heart rates on treadmill exercise test, without lowering blood pressure
• Ivabradine will increase percent pacing, and lower rates over time as shown on pacemaker diagnostic data
• Ivabradine will improve exertional symptoms and exercise tolerance due to atrial fibrillation as measured by the Borg's scale during a six-minute walk test.

Study Design

1. Patients with permanent atrial fibrillation will undergo baseline exercise treadmill test, measurement of heart rates and percent pacing from pacemaker diagnostics, and a 6 minute walk test with symptomatic assessment of dyspnea using the Borg's scale score.
2. Oral Ivabradine will be started at 5 mg twice daily, and up-titrated to a maximum dose of 7.5 mg twice daily at 7 days if percent pacing has not increased significantly or rates have not slowed more than 20bpm.
3. Exercise treadmill test, measurement of heart rates and percent pacing from pacemaker diagnostics, and a 6 minute walk test with symptomatic assessment of dyspnea using the Borg's scale score will be repeated at 2 weeks.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06405
      • Yale New Haven Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with stable blood pressures with permanent atrial fibrillation and implanted pacemaker pacing less than 50% of the time, with or without concomitant beta blocker or calcium channel blocker use

Exclusion Criteria:

• Patients with uncontrolled hypertension will be excluded
• To eliminate confounding effects, patients on Digoxin therapy will be excluded
• Patients on anti-arrhythmic therapy
• Patients with pre-excitation on EKG
• Patients who pace > 50% of the time
• Patients with severe Child-Pugh C hepatic impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ivabradine; Patients with permanent atrial fibrillation and previously implanted pacemakers who will be started on ivabradine.	Drug: Ivabradine; Ivabradine will be started and titrated to heart rate slowing of 20 bpm or greater, or an increase in pacing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate in Daily Life	Average ventricular heart rate derived using pacemaker interrogation over 2 weeks	2 weeks
Percent Pacing in Daily Life	Average percent pacing derived using pacemaker interrogation over 2 weeks	2 weeks
Heart Rate on Treadmill	Average ventricular heart rate will be recorded after the patient exercises on a treadmill using a heart rate monitor	2 weeks
Symptoms and Exercise Tolerance	Patients will undergo a 6 minute walk test, and symptoms and distance walked as measured by standard 6 minute walk protocol	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	Blood pressures will be monitored using a blood pressure cuff with the patient at rest for 10 minutes	2 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Rachel Lampert, MD, Yale University; Study Director: Hyon Jae Lee, MD, Yale New Haven Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2019
• Primary Completion (Actual): September 17, 2019
• Study Completion (Actual): September 17, 2019

Study Registration Dates

• First Submitted: May 31, 2019
• First Submitted That Met QC Criteria: June 13, 2019
• First Posted (Actual): June 14, 2019

Study Record Updates

• Last Update Posted (Actual): July 2, 2021
• Last Update Submitted That Met QC Criteria: June 30, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 2000022064

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No