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Rate Control in Atrial Fibrillation II (RATAFII)

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ClinicalTrials.gov Identifier: NCT02695992
Recruitment Status : Recruiting
First Posted : March 2, 2016
Last Update Posted : March 21, 2019
Sponsor:
Collaborators:
Vestre Viken Hospital Trust
Helse Sor-Ost
Information provided by (Responsible Party):
Sara Reinvik Ulimoen, Asker & Baerum Hospital

Tracking Information
First Submitted Date  ICMJE April 28, 2015
First Posted Date  ICMJE March 2, 2016
Last Update Posted Date March 21, 2019
Study Start Date  ICMJE February 2016
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2016)
  • Levels of NT-proBNP [ Time Frame: 4 weeks ]
    Levels of NT-proBNP will be measured at baseline and after 4 weeks to assess change
  • Levels of NT-proBNP [ Time Frame: 6 months ]
    Levels of NT-proBNP will be measured after 6 months
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02695992 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2018)
  • Exercise capacity defined as peak VO2 [ Time Frame: 4 weeks ]
    Exercise capacity will be assessed by cardiopulmonary exercise test at baseline and after 4 weeks to assess change
  • Exercise capacity defined as peak VO2 [ Time Frame: 6 months ]
    Exercise capacity will be assessed by cardiopulmonary exercise test after 6 months
  • Ventricular heart rate [ Time Frame: 4 weeks ]
    Ventricular heart rate will be assessed by ECG at rest and during exercise. Will be measured at baseline and after 4 weeks to assess change
  • Ventricular heart rate [ Time Frame: 6 months ]
    Ventricular heart rate will be assessed by ECG at rest and during exercise. Will be measured after 6 months.
  • Other biomarkers [ Time Frame: 4 weeks ]
    Levels of other biomarkers such as hs-troponins, hs-CRP will be measured at baseline and after 4 weeks to assess change
  • Other biomarkers [ Time Frame: 6 months ]
    Levels of other biomarkers such as hs-troponins, hs-CRP will be measured after 6 months.
  • Symptoms [ Time Frame: 4 weeks ]
    Symptoms will be assessed using a validated, self-administered questionnaire, the Symptom Checklist - Frequency and Severity (SCL). This will be filled out at baseline and 4 weeks to assess change.
  • Symptoms [ Time Frame: 6 months ]
    Symptoms will be assessed using a validated, self-administered questionnaire, the Symptom Checklist - Frequency and Severity (SCL). This will be filled out at 6 months.
  • Quality of life in SF-36 [ Time Frame: 4 weeks ]
    The SF-36 (Short Form 36 Health Survey) questionnaire assessing quality of life will be filled out at baseline and 4 weeks to assess change.
  • Quality of life in SF-36 [ Time Frame: 6 months ]
    The SF-36 questionnaire assessing quality of life will be filled out at 6 months.
  • Echocardiographic measures - Standard parasternal long axis and three apical views recordings. [ Time Frame: 4 weeks ]
    Will be done in the end expiratory phase with the subjects in supine lateral position. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Standard parasternal long axis and three apical views recordings. [ Time Frame: 6 months ]
    Will be done in the end expiratory phase with the subjects in supine lateral position. Measured at 6 months.
  • Echocardiographic measures - Left ventricular dimension, septal and posterior wall thickness. [ Time Frame: 4 weeks ]
    Will be measured as recommended by American Society of Echocardiography. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left ventricular dimension, septal and posterior wall thickness. [ Time Frame: 6 months ]
    Will be measured as recommended by American Society of Echocardiography. Measured at 6 months.
  • Echocardiographic measures - Left ventricular mass. [ Time Frame: 4 weeks ]
    Will be measured as recommended by American Society of Echocardiography. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left ventricular mass. [ Time Frame: 6 months ]
    Will be measured as recommended by American Society of Echocardiography. Measured at 6 months.
  • Echocardiographic measures - Left ventricular and left atrial maximal and minimal volumes. [ Time Frame: 4 weeks ]
    Will be calculated by 2D biplane and 4-chamber and 2D long axis views. (ml/m2). Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left ventricular and left atrial maximal and minimal volumes. [ Time Frame: 6 months ]
    Will be calculated by 2D biplane and 4-chamber and 2D long axis views. (ml/m2). Measured at 6 months.
  • Echocardiographic measures - Left ventricular ejection fraction will also be calculated. [ Time Frame: 4 weeks ]
    Using the modified Simpsons rule. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left ventricular ejection fraction will also be calculated. [ Time Frame: 6 months ]
    Using the modified Simpsons rule. Measured at 6 months.
  • Echocardiographic measures - Transmitral flow and pulmonary venous flow. [ Time Frame: 4 weeks ]
    Will be assessed by pulsed Doppler. Tissue Doppler imaging-derived indices will be recorded at the base of the septal and lateral mitral annulus. (cm/s). Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Transmitral flow and pulmonary venous flow. [ Time Frame: 6 months ]
    Will be assessed by pulsed Doppler. Tissue Doppler imaging-derived indices will be recorded at the base of the septal and lateral mitral annulus. (cm/s). Measured at 6 months.
  • Echocardiographic measures - Global and regional longitudinal left ventricular strain. [ Time Frame: 4 weeks ]
    Will be analysed by a semi-automated speckle tracking technique. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Global and regional longitudinal left ventricular strain. [ Time Frame: 6 months ]
    Will be analysed by a semi-automated speckle tracking technique.Measured at 6 months.
  • Echocardiographic measures - Left atrial deformation for assessment of global as well as regional left atrial strain. [ Time Frame: 4 weeks ]
    Will be analysed by a semi-automated speckle tracking technique. Characterizing both reservoir and conduit function. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left atrial deformation for assessment of global as well as regional left atrial strain. [ Time Frame: 6 months ]
    Will be analysed by a semi-automated speckle tracking technique. Characterizing both reservoir and conduit function. Measured at 6 months.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2016)
  • Exercise capacity defined as peak VO2 [ Time Frame: 4 weeks ]
    Exercise capacity will be assessed by cardiopulmonary exercise test at baseline and after 4 weeks to assess change
  • Exercise capacity defined as peak VO2 [ Time Frame: 6 months ]
    Exercise capacity will be assessed by cardiopulmonary exercise test after 6 months
  • Ventricular heart rate [ Time Frame: 4 weeks ]
    Ventricular heart rate will be assessed by ECG at rest and during exercise. Will be measured at baseline and after 4 weeks to assess change
  • Ventricular heart rate [ Time Frame: 6 months ]
    Ventricular heart rate will be assessed by ECG at rest and during exercise. Will be measured after 6 months.
  • Other biomarkers [ Time Frame: 4 weeks ]
    Levels of other biomarkers such as hs-troponins, hs-CRP will be measured at baseline and after 4 weeks to assess change
  • Other biomarkers [ Time Frame: 6 months ]
    Levels of other biomarkers such as hs-troponins, hs-CRP will be measured after 6 months.
  • Symptoms [ Time Frame: 4 weeks ]
    Symptoms will be assessed using a validated, self-administered questionnaire, the Symptom Checklist - Frequency and Severity (SCL). This will be filled out at baseline and 4 weeks to assess change.
  • Symptoms [ Time Frame: 6 months ]
    Symptoms will be assessed using a validated, self-administered questionnaire, the Symptom Checklist - Frequency and Severity (SCL). This will be filled out at 6 months.
  • Quality of life [ Time Frame: 4 weeks ]
    The SF-36 (Short Form 36 Health Survey) questionnaire assessing quality of life will be filled out at baseline and 4 weeks to assess change.
  • Quality of life [ Time Frame: 6 months ]
    The SF-36 questionnaire assessing quality of life will be filled out at 6 months.
  • Echocardiographic measures - Standard parasternal long axis and three apical views recordings. [ Time Frame: 4 weeks ]
    Will be done in the end expiratory phase with the subjects in supine lateral position. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Standard parasternal long axis and three apical views recordings. [ Time Frame: 6 months ]
    Will be done in the end expiratory phase with the subjects in supine lateral position. Measured at 6 months.
  • Echocardiographic measures - Left ventricular dimension, septal and posterior wall thickness. [ Time Frame: 4 weeks ]
    Will be measured as recommended by American Society of Echocardiography. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left ventricular dimension, septal and posterior wall thickness. [ Time Frame: 6 months ]
    Will be measured as recommended by American Society of Echocardiography. Measured at 6 months.
  • Echocardiographic measures - Left ventricular mass. [ Time Frame: 4 weeks ]
    Will be measured as recommended by American Society of Echocardiography. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left ventricular mass. [ Time Frame: 6 months ]
    Will be measured as recommended by American Society of Echocardiography. Measured at 6 months.
  • Echocardiographic measures - Left ventricular and left atrial maximal and minimal volumes. [ Time Frame: 4 weeks ]
    Will be calculated by 2D biplane and 4-chamber and 2D long axis views. (ml/m2). Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left ventricular and left atrial maximal and minimal volumes. [ Time Frame: 6 months ]
    Will be calculated by 2D biplane and 4-chamber and 2D long axis views. (ml/m2). Measured at 6 months.
  • Echocardiographic measures - Left ventricular ejection fraction will also be calculated. [ Time Frame: 4 weeks ]
    Using the modified Simpsons rule. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left ventricular ejection fraction will also be calculated. [ Time Frame: 6 months ]
    Using the modified Simpsons rule. Measured at 6 months.
  • Echocardiographic measures - Transmitral flow and pulmonary venous flow. [ Time Frame: 4 weeks ]
    Will be assessed by pulsed Doppler. Tissue Doppler imaging-derived indices will be recorded at the base of the septal and lateral mitral annulus. (cm/s). Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Transmitral flow and pulmonary venous flow. [ Time Frame: 6 months ]
    Will be assessed by pulsed Doppler. Tissue Doppler imaging-derived indices will be recorded at the base of the septal and lateral mitral annulus. (cm/s). Measured at 6 months.
  • Echocardiographic measures - Global and regional longitudinal left ventricular strain. [ Time Frame: 4 weeks ]
    Will be analysed by a semi-automated speckle tracking technique. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Global and regional longitudinal left ventricular strain. [ Time Frame: 6 months ]
    Will be analysed by a semi-automated speckle tracking technique.Measured at 6 months.
  • Echocardiographic measures - Left atrial deformation for assessment of global as well as regional left atrial strain. [ Time Frame: 4 weeks ]
    Will be analysed by a semi-automated speckle tracking technique. Characterizing both reservoir and conduit function. Will be measured at baseline and after 4 weeks to assess change
  • Echocardiographic measures - Left atrial deformation for assessment of global as well as regional left atrial strain. [ Time Frame: 6 months ]
    Will be analysed by a semi-automated speckle tracking technique. Characterizing both reservoir and conduit function. Measured at 6 months.
Current Other Pre-specified Outcome Measures
 (submitted: February 25, 2016)
  • Blood pressure [ Time Frame: 4 weeks ]
    Blood pressure will be measured at baseline and after 4 weeks to assess change
  • Blood pressure [ Time Frame: 6 months ]
    Blood pressure will be measured after 6 months
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Rate Control in Atrial Fibrillation II
Official Title  ICMJE Rate Control in Atrial Fibrillation II
Brief Summary

The RATAF II study is a randomized, prospective, parallel group study, designed to compare the effects of two different drug regimens for rate control in permanent AF (atrial fibrillation). We will investigate on the difference in effects on exercise capacity, biomarkers (NT-proBNP (N-terminal pro-brain natriuretic peptide), troponins, hs-CRP), heart rate, echocardiographic measurements and symptoms.

Our main hypothesis is that six months' treatment with the calcium channel blocker diltiazem will lower NT-proBNP and increase exercise capacity (peak VO2) compared to treatment with the beta blocker metoprolol in permanent AF.

Detailed Description

Atrial fibrillation is a common cardiac disease, with increasing incidence and prevalence. There are two main treatment strategies for this arrhythmia, rhythm control and rate control. As rate control is easier to achieve and no major difference in outcome has been found between these two strategies, it is considered a reasonable initial treatment for the majority of AF patients.

Reduced exercise capacity is the most prevalent symptom in patients with permanent AF. In the first Rate control in Atrial Fibrillation (RATAF) study, we demonstrated that calcium channel blockers preserved exercise capacity, reduced arrhythmia-related symptoms and lowered levels of NT-proBNP - whereas the beta blockers reduced the exercise capacity, did not reduce arrhythmia-related symptoms and increased NT-proBNP.

These findings are relevant to a large proportion of patients with permanent AF, suggesting that calcium channel blockers should be the first drug of choice for rate control in patients without heart failure or coronary heart disease. Our results challenge the current widespread use of beta blockers in this setting. However, as the follow up time in the RATAF study was only 3 weeks, it is not clear if these effects are sustained over time. Furthermore, we do not know the mechanisms for the differential effects on exercise capacity, arrhythmia related symptoms and NT-proBNP levels.

In the RATAF II study we will investigate whether the effects on NT-proBNP levels, exercise capacity and symptoms are sustained over time, and explore potential mechanisms that may explain the difference in these effects. The study will provide new insights and results relevant for everyday clinical practice and be of importance for a large and growing group of patients.

A total of 240 patients will be included. Eligible patients will be recruited from the out-patient clinics at the participation hospitals and through advertisements in local newspapers. After inclusion and a wash-out period of 14 days free from drugs affecting the heart rate, patients will be examined by echocardiography, 12-lead ECG (electrocardiography), 24h Holter monitoring, maximal cardiopulmonary exercise test and venous blood sampling at rest, at maximal exercise and after recovery. Perceived arrhythmia related symptoms, quality of life and level of physical activity will be assessed using self-administered questionnaires.

Participants will be randomized through a computer-generated randomization list, to receive one of the study drug regimens; metoprolol 100 mg o.d. or diltiazem 360 mg o.d. The investigators and study personnel will be blinded with regard to allocated study drug. The participants themselves will know what study drug they are assigned. Also, study personnel not involved in examinations will also be able to acquire knowledge concerning assigned study drug, to ensure the process of dosage in the startup phase, assess adverse events (AE) and side effects throughout the study.

Examinations will be repeated after four weeks and six months. All examinations will be performed at the Department of Medical Research, Baerum Hospital to ensure standardized procedures.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Atrial Fibrillation
  • Permanent Atrial Fibrillation
Intervention  ICMJE
  • Drug: Metoprolol
    Dosage 100 mg o.d.
    Other Name: Selo-Zok Metoprolol Astra Zeneca depot
  • Drug: Diltiazem
    Dosage 360 mg o.d.
    Other Name: Cardizem Diltiazem Uno depot
Study Arms  ICMJE
  • Active Comparator: Metoprolol
    Metoprolol, extended release tablets. 100 mg daily
    Intervention: Drug: Metoprolol
  • Active Comparator: Diltiazem
    Diltiazem, extended release tablets. 360 mg daily
    Intervention: Drug: Diltiazem
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 25, 2016)
240
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Above 18 years of age
  • Symptomatic, permanent AF of at least three months duration
  • Resting heart rate ≥80 bpm
  • Signed informed consent

Exclusion Criteria:

  • Congestive heart failure
  • Ischemic heart disease
  • Hypotension (Systolic blood pressure <100 mmHg)
  • Treatment with class I or III antiarrhythmic drugs
  • Severe hepatic or renal failure
  • Pregnancy or lactation
  • Hypersensitivity or contradictions to study drugs
  • Atrio-ventricular conduction disturbances
  • Thyrotoxicosis
  • Life limiting disease or substance abuse which may affect participation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sara Reinvik Ulimoen, MD PhD 0047 41511811 sara.ulimoen@gmail.com
Contact: Katrine Enge, MD 0047 91622668 katrine.enge@gmail.com
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02695992
Other Study ID Numbers  ICMJE 240415
2015-001918-98 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sara Reinvik Ulimoen, Asker & Baerum Hospital
Study Sponsor  ICMJE Asker & Baerum Hospital
Collaborators  ICMJE
  • Vestre Viken Hospital Trust
  • Helse Sor-Ost
Investigators  ICMJE
Principal Investigator: Sara Reinvik Ulimoen, MD PhD Vestre Viken HF Baerum Hospital
PRS Account Asker & Baerum Hospital
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP