Rate Control Versus Rhythm Control For Postoperative Atrial Fibrillation

The purpose of this study is to compare the therapeutic strategies of rate control versus rhythm control in cardiac surgery patients who develop in-hospital postoperative atrial fibrillation or atrial flutter (AF). In patients who develop AF during hospitalization after cardiac surgery, the hypothesis is that a strategy of rhythm control will reduce days in hospital within 60 days of the occurrence of AF compared to a strategy of rate control.

Study Overview

• Status: Completed
• Conditions: Postoperative Atrial Fibrillation
• Intervention / Treatment: Drug: Amiodarone; Procedure: DC-cardioversion; Drug: Rate Control

Detailed Description

The purpose of the research is to compare two strategies for treating atrial fibrillation or atrial flutter, both of which are referred to as AF, after cardiac surgery. AF is the most common complication after cardiac surgery. AF is when the upper chambers of the heart (atria) experience disorganized electrical activity which causes the heart beat to be irregular. The two treatment strategies to be used in this study are called rhythm control and rate control. The rhythm control strategy will attempt to bring the heart beat back to a regular rhythm using treatments known and approved to control heart rhythm. The rate control strategy will attempt to bring the heart rate to less than 100 beats per minute at rest using medications known and recommended to control heart rate. Both strategies are commonly used to treat AF. All of the medications that will be used in this study are the standard of care for use in patients experiencing AF. This research seeks to determine whether rhythm control is better than rate control in patients with AF after cardiac surgery.

• Study Type: Interventional
• Enrollment (Actual): 523
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hôpital du Sacré-Coeur de Montréal
    • Montreal, Quebec, Canada, H2W 1T8
      • Centre Hospitalier de l'Universite de Montreal
    • Montréal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Bethesda, Maryland, United States, 20814
      • NIH Heart Center at Suburban Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health Services
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Einstein Heart Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Plano, Texas, United States, 75093
      • Baylor Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health Systems
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Enrollment Inclusion Criteria:

• Age > 18 years
• Undergoing heart surgery for coronary artery bypass (on-pump or off-pump CABG) and/or valve repair or replacement (excluding mechanical valves), including re-operations
• Hemodynamically stable

Randomization Inclusion Criteria

• AF that persists for > 60 minutes or recurrent (more than one) episodes of AF up to 7 days after surgery during the index hospitalization.

Exclusion Criteria:

• LVAD insertion or heart transplantation
• Maze procedure
• TAVR
• History of or planned mechanical valve replacement
• Correction of complex congenital cardiac defect (excluding bicuspid aortic valve, atrial septal defect or PFO)
• History of AF or AFL
• History of AF or AFL ablation
• Contraindications to warfarin or amiodarone
• Need for long-term anticoagulation
• Concurrent participation in an interventional (drug or device) trial

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: Rhythm control; Rhythm Control in post-operative AF Amiodarone and/or DC-cardioversion Amiodarone Initial Dose; Oral: 400 mg po TID for 3 days is recommended; For patients incapable of taking oral: 150 mg IV bolus over 10 min, then 1 mg/min over 6 hours followed by 0.5 mg/min over 18 hours Maintenance Dose; Oral: at least 200 mg/day to be continued until 60 days after randomization; If drug cannot be given orally or via NG tube: 0.5 mg/min administered through central line (e.g., PICC) until oral dosing is started DC-Cardioversion - frequency and duration determined by medical professional as medically needed	Drug: Amiodarone; Amiodarone Initial Dose; Oral: 400 mg po TID for 3 days is recommended; For patients incapable of taking oral: 150 mg IV bolus over 10 min, then 1 mg/min over 6 hours followed by 0.5 mg/min over 18 hours Maintenance Dose; Oral: at least 200 mg/day to be continued until 60 days after randomization; If drug cannot be given orally or via NG tube: 0.5 mg/min administered through central line (e.g., PICC) until oral dosing is started; Other Names: Cordarone; Procedure: DC-cardioversion; DC-Cardioversion - frequency and duration determined by medical professional as medically needed; Other Names: Direct Current Cardioversion
Active Comparator: Rate control; Rate Control in post-operative AF Beta-blocker and/or Calcium channel blockers and/or Digoxin Dose, frequency and duration determined by medical professional as medically needed	Drug: Rate Control; Beta-blocker and/or Calcium channel blockers and/or Digoxin - Dose, frequency and duration determined by medical professional as medically needed; Other Names: Digoxin; Beta-blocker; Calcium channel blockers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Days in Hospital	The total number of days in hospital for any hospitalization that occurs within 60 days of randomization to AF treatment strategy.	Within 60 days of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Conversion to Sustained, Stable Non-AF Rhythm		Up to index hospital discharge or 7 days post surgery, whichever came first
Heart Rhythm Comparison	Compare heart rhythm (number of patients in sustained, stable non-AF rhythm) between treatment arms at hospital discharge	Hospital discharge
Heart Rhythm Comparison	Compare heart rhythm (patients in sustained, stable non-AF rhythm) between treatment arms at 30 days after randomization	30 days after randomization
Heart Rhythm Comparison	Compare heart rhythm (number of patients in sustained, stable non-AF rhythm) between treatment arms at 60 days after randomization	60 days after randomization
Length of Stay (Index Hospitalization)	Overall length of stay for the index hospitalization	Within 60 days post surgery
Length of Stay (Rehospitalization, Including ED Visits)	Compare length of stay between groups for any cause and AF-related hospitalizations, including ED visits	Within 60 days of randomization
Outpatient Interventions	Compare frequency of outpatient visits between groups for any cause and AF-related causes	Within 60 days of randomization
AF- or Treatment-related Events		Within 60 days of randomization
Cost (Hospital)	Compare cost of index hospitalization and cost of rehospitalizations (including ED visits) between groups	Within 60 days of randomization

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Canadian Institutes of Health Research (CIHR); National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Study Chair: Richard Wiesel, MD, Cardiothoracic Surgical Trials Network; Study Chair: Patrick T O'Gara, MD, Cardiothoracic Surgical Trials Network

Publications and helpful links

General Publications

• Afifi A. CTS trials network: Rate control vs rhythm control for atrial fibrillation after cardiac surgery - Do bitter pills have blessed effects? Glob Cardiol Sci Pract. 2016 Jun 30;2016(2):e201615. doi: 10.21542/gcsp.2016.15.
• Gillinov AM, Bagiella E, Moskowitz AJ, Raiten JM, Groh MA, Bowdish ME, Ailawadi G, Kirkwood KA, Perrault LP, Parides MK, Smith RL 2nd, Kern JA, Dussault G, Hackmann AE, Jeffries NO, Miller MA, Taddei-Peters WC, Rose EA, Weisel RD, Williams DL, Mangusan RF, Argenziano M, Moquete EG, O'Sullivan KL, Pellerin M, Shah KJ, Gammie JS, Mayer ML, Voisine P, Gelijns AC, O'Gara PT, Mack MJ; CTSN. Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery. N Engl J Med. 2016 May 19;374(20):1911-21. doi: 10.1056/NEJMoa1602002. Epub 2016 Apr 4.

Helpful Links

• Cardiothoracic Surgical Trials Network Website

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: May 5, 2014
• First Submitted That Met QC Criteria: May 5, 2014
• First Posted (Estimate): May 7, 2014

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: February 28, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Cardiac surgery; Mitral valve surgery; Heart surgery; Coronary artery bypass; Cardiac arrhythmia; Atrial flutter; Valve surgery; Aortic valve surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Calcium-Regulating Hormones and Agents; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Potassium Channel Blockers; Digoxin; Amiodarone; Calcium Channel Blockers
• Other Study ID Numbers: GCO 08-1078-00007; 5U01HL088942-08 (U.S. NIH Grant/Contract)