Lenient Rate Control Versus Strict Rate Control for Atrial Fibrillation. The Danish Atrial Fibrillation Randomised Clinical Trial (DanAF)

Lenient Rate Control Versus Strict Rate Control for Atrial Fibrillation. The Danish Atrial Fibrillation (DanAF) Randomised Clinical Trial

Atrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. The comparable effects of a lenient rate control strategy and a strict rate control strategy in patients with atrial fibrillation are uncertain and only one trial has assessed this previously in patients with permanent atrial fibrillation.

The investigators will therefore undertake a randomised, superiority trial at four hospitals in Denmark.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Atrial Fibrillation, Persistent; Atrial Fibrillation Chronic
• Intervention / Treatment: Other: Rate control

• Study Type: Interventional
• Enrollment (Anticipated): 350
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joshua Feinberg, MD; Phone Number: +45 59484530; Email: jorf@regionsjaelland.dk

Study Locations

• Denmark
  • Holbæk, Denmark, 4300
    • Recruiting
    • Holbæk Hospital
    • Contact: Joshua B Feinberg, MD; Phone Number: 004550587215
    • Principal Investigator: Ilan Raymond, MD
  • Hvidovre, Denmark, 2650
    • Not yet recruiting
    • Hvidovre University Hospital
    • Principal Investigator: Ulrik Dixen, Prof
  • Odense, Denmark, 5000
    • Not yet recruiting
    • Odense University Hospital
    • Principal Investigator: Axel Brandes, prof.
  • Roskilde, Denmark, 4000
    • Not yet recruiting
    • Zealand University Hospital - Roskilde
    • Principal Investigator: Ole D Pedersen, DMSc
    • Sub-Investigator: Uffe Gang, MD

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:

1. Participants with atrial fibrillation (ECG confirmed and diagnosed by the treatment provider) who at inclusion have either persistent (defined as atrial fibrillation for more than 7days) or permanent atrial fibrillation (only rate control is considered going forward).
2. Rate control must be accepted as being the primary management strategy going forward. Consideration towards whether rhythm control is more appropriate must be considered, especially given the results of the Early treatment of Atrial fibrillation for Stroke prevention Trial (EAST).
3. Informed consent.
4. Adult (18 years or older).

Exclusion Criteria:

1. No informed consent.
2. Initial heart rate under 80 bpm at rest (assessed via ECG before randomisation).
3. Less than 3 weeks of anticoagulation with new oral anticoagulants or 4 weeks with efficient warfarin if indicated.
4. If the treating physician deems that the participant is not fit to be randomised into both groups based on an individual assessment. Such a decision will be made before randomisation by the treating physician. This can e.g. be participants dependent on a high ventricular rate to maintain a sufficient cardiac output. Such participants could be participants with heart failure, participants with a hemodynamically significant valve dysfunction, or severely dehydrated participants.
5. Participants who are haemodynamically unstable and therefore require immediate electrical cardioversion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lenient rate control; Treating physicians will target a resting heart rate between 80 and 110 beats per minute on a 12-lead resting ECG measured over 1 minute after 5 minutes of rest.	Other: Rate control; Treatment will be provided according to current guidelines and as such the algorithm for treatment will be differentiated based on the status of left ventricular ejection fraction. For participants with reduced left ventricular ejection fraction, beta-blockers (metoprolol and bisoprolol) will be the primary therapy. Secondary therapies may include digoxin or amiodarone. For participants with preserved left ventricular ejection fraction, the primary therapy will be beta-blockers (metoprolol and bisoprolol) or non-dihydropyridine calcium-channel blockers (verapamil) with secondary therapy consisting of digoxin or amiodarone. Pacing therapies, alone or with atrioventricular node ablation, are utilised as indicated in the view of the treating physician.
ACTIVE_COMPARATOR: Strict rate control; Treating physicians will target a resting heart rate a mean resting heart rate < 80 bpm on a 12-lead resting ECG measured over 1 minute after 5 minutes of rest.	Other: Rate control; Treatment will be provided according to current guidelines and as such the algorithm for treatment will be differentiated based on the status of left ventricular ejection fraction. For participants with reduced left ventricular ejection fraction, beta-blockers (metoprolol and bisoprolol) will be the primary therapy. Secondary therapies may include digoxin or amiodarone. For participants with preserved left ventricular ejection fraction, the primary therapy will be beta-blockers (metoprolol and bisoprolol) or non-dihydropyridine calcium-channel blockers (verapamil) with secondary therapy consisting of digoxin or amiodarone. Pacing therapies, alone or with atrioventricular node ablation, are utilised as indicated in the view of the treating physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Short Form-36 (SF-36) physical component score	After 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Days alive outside hospital	After 6 months
Atrial Fibrillation Effect on Quality of Life (AFEQT)	After 1 year
Short Form-36 (SF-36) mental component score	1 year
Serious adverse events	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate		1 year
Cardiac mortality		1 year
All-cause mortality	Mortality regardless of cause.	1 year
All-cause mortality	Mortality regardless of cause.	2 year
All-cause mortality	Mortality regardless of cause.	After 3 years
Composite of all-cause mortality, stroke, myocardial infarction and cardiac arrest.		1 year
Composite of all-cause mortality, stroke, myocardial infarction and cardiac arrest.		2 year
Composite of all-cause mortality, stroke, myocardial infarction and cardiac arrest.		After 3 years
Cardiac mortality		2 year
Cardiac mortality		After 3 years
Stroke	ICD-10 codes I60-I63.	1 year
Stroke	ICD-10 codes I60-I63.	2 year
Stroke	ICD-10 codes I60-I63.	After 3 years
Hospitalisation for worsening of heart failure		1 year
Hospitalisation for worsening of heart failure		2 year
Hospitalisation for worsening of heart failure		After 3 years
Number of hospital admissions		1 year
Number of hospital admissions		2 year
Number of hospital admissions		After 3 years
Six-minute walking distance		1 year
Six-minute walking distance		2 year
Six-minute walking distance		After 3 years
Physical activity measured using a trial accelerometer or similar		1 year
Physical activity measured using a trial accelerometer or similar		2 year
Physical activity measured using a trial accelerometer or similar		After 3 years
Presence of sleep apnoea		1 year
Presence of sleep apnoea		2 year
Presence of sleep apnoea		After 3 years
Heart rate		2 year
Heart rate		After 3 years
Healthcare costs		1 year
Healthcare costs		2 year
Healthcare costs		After 3 years
Various biomarkers		1 year
Various biomarkers		2 year
Various biomarkers		After 3 years
Switch to rhythm control strategy		1 year
Switch to rhythm control strategy		2 year
Switch to rhythm control strategy		After 3 years
Implantation of a pacemaker or cardioverter-defibrillator		1 year
Implantation of a pacemaker or cardioverter-defibrillator		2 year
Implantation of a pacemaker or cardioverter-defibrillator		After 3 years
The questionnaire WorkQ		1 year
The questionnaire WorkQ		2 year
The questionnaire WorkQ		After 3 years
Echocardiography - Left ventricle dimensions		After 1 year
Echocardiography - Left ventricle dimensions		After 2 years
Echocardiography - Left ventricle dimensions		After 3 years
Echocardiography - systolic and diastolic function		After 1 year
Echocardiography - systolic and diastolic function		After 2 years
Echocardiography - systolic and diastolic function		After 3 years
Echocardiography - Right ventricle dimension		After 1 year
Echocardiography - Right ventricle dimension		After 2 years
Echocardiography - Right ventricle dimension		After 3 years
Echocardiography - Atrial dimensions		After 1 year
Echocardiography - Atrial dimensions		After 2 years
Echocardiography - Atrial dimensions		After 3 years
Echocardiography - pulmonary pressure		After 1 year
Echocardiography - pulmonary pressure		After 2 years
Echocardiography - pulmonary pressure		After 3 years
Short Form-36 (SF-36) physical component score		After 2 years
Short Form-36 (SF-36) physical component score		After 3 years
Days alive outside hospital		After 1 year
Days alive outside hospital		After 2 years
Days alive outside hospital		After 3 years
Atrial Fibrillation Effect on Quality of Life (AFEQT)		After 2 years
Atrial Fibrillation Effect on Quality of Life (AFEQT)		After 3 years
Short Form-36 (SF-36) mental component score		After 2 years
Short Form-36 (SF-36) mental component score		After 3 years
Serious adverse events		After 2 years
Serious adverse events		After 3 years

Collaborators and Investigators

• Sponsor: Holbaek Sygehus
• Collaborators: Odense University Hospital; Zealand University Hospital; Hvidovre University Hospital
• Investigators: Principal Investigator: Joshua Feinberg, MD, Holbaek University Hospital/University of Southern Denmark

Publications and helpful links

General Publications

• Feinberg JB, Olsen MH, Brandes A, Raymond L, Nielsen WB, Nielsen EE, Stensgaard-Hansen F, Dixen U, Pedersen OD, Gang UJO, Gluud C, Jakobsen JC. Lenient rate control versus strict rate control for atrial fibrillation: a protocol for the Danish Atrial Fibrillation (DanAF) randomised clinical trial. BMJ Open. 2021 Mar 31;11(3):e044744. doi: 10.1136/bmjopen-2020-044744.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 31, 2021
• Primary Completion (ANTICIPATED): March 2, 2026
• Study Completion (ANTICIPATED): March 2, 2026

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (ACTUAL): September 9, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Rate control
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: REG-078-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share anonymised data in a data repository.
• IPD Sharing Time Frame: Not possible to describe yet but will be made available within a timely manner after publication of results.
• IPD Sharing Access Criteria: Sharing will abide by the General Data Protection Regulation and the Danish data protections laws.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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