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

Primary Purpose

Atrial Fibrillation, Persistent, Atrial Fibrillation Chronic, Atrial Fibrillation

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Rate control
Sponsored by
Holbaek Sygehus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation, Persistent focused on measuring Rate control

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Holbรฆk HospitalRecruiting
  • Hvidovre University Hospital
  • Odense University Hospital
  • Zealand University Hospital - Roskilde

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Lenient rate control

Strict rate control

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Short Form-36 (SF-36) physical component score

Secondary Outcome Measures

Days alive outside hospital
Atrial Fibrillation Effect on Quality of Life (AFEQT)
Short Form-36 (SF-36) mental component score
Serious adverse events

Full Information

First Posted
August 26, 2020
Last Updated
March 15, 2022
Sponsor
Holbaek Sygehus
Collaborators
Odense University Hospital, Hvidovre University Hospital, Zealand University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04542785
Brief Title
Lenient Rate Control Versus Strict Rate Control for Atrial Fibrillation. The Danish Atrial Fibrillation Randomised Clinical Trial
Acronym
DanAF
Official Title
Lenient Rate Control Versus Strict Rate Control for Atrial Fibrillation. The Danish Atrial Fibrillation (DanAF) Randomised Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 31, 2021 (Actual)
Primary Completion Date
March 2, 2026 (Anticipated)
Study Completion Date
March 2, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Holbaek Sygehus
Collaborators
Odense University Hospital, Hvidovre University Hospital, Zealand University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Persistent, Atrial Fibrillation Chronic, Atrial Fibrillation
Keywords
Rate control

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
Outcome assessors will be blinded. Participants will not be informed of the heart rate target or actual heart rate. Treatment providers managing the heart rate target will not be blinded as the intervention requires information of the heart rate. Other treatment providers will not be informed of the heart rate target.
Allocation
Randomized
Enrollment
350 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lenient rate control
Arm Type
Experimental
Arm Description
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.
Arm Title
Strict rate control
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Rate control
Intervention Description
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.
Primary Outcome Measure Information:
Title
Short Form-36 (SF-36) physical component score
Time Frame
After 1 year
Secondary Outcome Measure Information:
Title
Days alive outside hospital
Time Frame
After 6 months
Title
Atrial Fibrillation Effect on Quality of Life (AFEQT)
Time Frame
After 1 year
Title
Short Form-36 (SF-36) mental component score
Time Frame
1 year
Title
Serious adverse events
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
All-cause mortality
Description
Mortality regardless of cause.
Time Frame
1 year
Title
All-cause mortality
Description
Mortality regardless of cause.
Time Frame
2 year
Title
All-cause mortality
Description
Mortality regardless of cause.
Time Frame
After 3 years
Title
Composite of all-cause mortality, stroke, myocardial infarction and cardiac arrest.
Time Frame
1 year
Title
Composite of all-cause mortality, stroke, myocardial infarction and cardiac arrest.
Time Frame
2 year
Title
Composite of all-cause mortality, stroke, myocardial infarction and cardiac arrest.
Time Frame
After 3 years
Title
Cardiac mortality
Time Frame
1 year
Title
Cardiac mortality
Time Frame
2 year
Title
Cardiac mortality
Time Frame
After 3 years
Title
Stroke
Description
ICD-10 codes I60-I63.
Time Frame
1 year
Title
Stroke
Description
ICD-10 codes I60-I63.
Time Frame
2 year
Title
Stroke
Description
ICD-10 codes I60-I63.
Time Frame
After 3 years
Title
Hospitalisation for worsening of heart failure
Time Frame
1 year
Title
Hospitalisation for worsening of heart failure
Time Frame
2 year
Title
Hospitalisation for worsening of heart failure
Time Frame
After 3 years
Title
Number of hospital admissions
Time Frame
1 year
Title
Number of hospital admissions
Time Frame
2 year
Title
Number of hospital admissions
Time Frame
After 3 years
Title
Six-minute walking distance
Time Frame
1 year
Title
Six-minute walking distance
Time Frame
2 year
Title
Six-minute walking distance
Time Frame
After 3 years
Title
Physical activity measured using a trial accelerometer or similar
Time Frame
1 year
Title
Physical activity measured using a trial accelerometer or similar
Time Frame
2 year
Title
Physical activity measured using a trial accelerometer or similar
Time Frame
After 3 years
Title
Presence of sleep apnoea
Time Frame
1 year
Title
Presence of sleep apnoea
Time Frame
2 year
Title
Presence of sleep apnoea
Time Frame
After 3 years
Title
Heart rate
Time Frame
1 year
Title
Heart rate
Time Frame
2 year
Title
Heart rate
Time Frame
After 3 years
Title
Healthcare costs
Time Frame
1 year
Title
Healthcare costs
Time Frame
2 year
Title
Healthcare costs
Time Frame
After 3 years
Title
Various biomarkers
Time Frame
1 year
Title
Various biomarkers
Time Frame
2 year
Title
Various biomarkers
Time Frame
After 3 years
Title
Switch to rhythm control strategy
Time Frame
1 year
Title
Switch to rhythm control strategy
Time Frame
2 year
Title
Switch to rhythm control strategy
Time Frame
After 3 years
Title
Implantation of a pacemaker or cardioverter-defibrillator
Time Frame
1 year
Title
Implantation of a pacemaker or cardioverter-defibrillator
Time Frame
2 year
Title
Implantation of a pacemaker or cardioverter-defibrillator
Time Frame
After 3 years
Title
The questionnaire WorkQ
Time Frame
1 year
Title
The questionnaire WorkQ
Time Frame
2 year
Title
The questionnaire WorkQ
Time Frame
After 3 years
Title
Echocardiography - Left ventricle dimensions
Time Frame
After 1 year
Title
Echocardiography - Left ventricle dimensions
Time Frame
After 2 years
Title
Echocardiography - Left ventricle dimensions
Time Frame
After 3 years
Title
Echocardiography - systolic and diastolic function
Time Frame
After 1 year
Title
Echocardiography - systolic and diastolic function
Time Frame
After 2 years
Title
Echocardiography - systolic and diastolic function
Time Frame
After 3 years
Title
Echocardiography - Right ventricle dimension
Time Frame
After 1 year
Title
Echocardiography - Right ventricle dimension
Time Frame
After 2 years
Title
Echocardiography - Right ventricle dimension
Time Frame
After 3 years
Title
Echocardiography - Atrial dimensions
Time Frame
After 1 year
Title
Echocardiography - Atrial dimensions
Time Frame
After 2 years
Title
Echocardiography - Atrial dimensions
Time Frame
After 3 years
Title
Echocardiography - pulmonary pressure
Time Frame
After 1 year
Title
Echocardiography - pulmonary pressure
Time Frame
After 2 years
Title
Echocardiography - pulmonary pressure
Time Frame
After 3 years
Title
Short Form-36 (SF-36) physical component score
Time Frame
After 2 years
Title
Short Form-36 (SF-36) physical component score
Time Frame
After 3 years
Title
Days alive outside hospital
Time Frame
After 1 year
Title
Days alive outside hospital
Time Frame
After 2 years
Title
Days alive outside hospital
Time Frame
After 3 years
Title
Atrial Fibrillation Effect on Quality of Life (AFEQT)
Time Frame
After 2 years
Title
Atrial Fibrillation Effect on Quality of Life (AFEQT)
Time Frame
After 3 years
Title
Short Form-36 (SF-36) mental component score
Time Frame
After 2 years
Title
Short Form-36 (SF-36) mental component score
Time Frame
After 3 years
Title
Serious adverse events
Time Frame
After 2 years
Title
Serious adverse events
Time Frame
After 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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). 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). Informed consent. Adult (18 years or older). Exclusion Criteria: No informed consent. Initial heart rate under 80 bpm at rest (assessed via ECG before randomisation). Less than 3 weeks of anticoagulation with new oral anticoagulants or 4 weeks with efficient warfarin if indicated. 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. Participants who are haemodynamically unstable and therefore require immediate electrical cardioversion
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joshua Feinberg, MD
Phone
+45 59484530
Email
jorf@regionsjaelland.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua Feinberg, MD
Organizational Affiliation
Holbaek University Hospital/University of Southern Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Holbรฆk Hospital
City
Holbรฆk
ZIP/Postal Code
4300
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua B Feinberg, MD
Phone
004550587215
First Name & Middle Initial & Last Name & Degree
Ilan Raymond, MD
Facility Name
Hvidovre University Hospital
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulrik Dixen, Prof
Facility Name
Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Axel Brandes, prof.
Facility Name
Zealand University Hospital - Roskilde
City
Roskilde
ZIP/Postal Code
4000
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ole D Pedersen, DMSc
First Name & Middle Initial & Last Name & Degree
Uffe Gang, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
33789853
Citation
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.
Results Reference
derived

Learn more about this trial

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

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