- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00133211
Radiofrequency Ablation (RFA) Versus Antiarrhythmic Drug Treatment in Paroxysmal Atrial Fibrillation (MANTRA-PAF)
Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation: A Randomized Prospective Multicentre Study (MANTRA-PAF)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Introduction:
Atrial fibrillation is by far the most common heart arrhythmia and is even increasing in prevalence and incidence. Approximately 10% of all cardiologic hospitalizations are due to atrial fibrillation. Several studies have shown older patients with paroxysmal or persistent atrial fibrillation and with minor symptoms related to the arrhythmia do equally well on a frequency control as compared to a rhythm control strategy. However, some of this lack of difference in outcome may be because the benefits by achieving sinus rhythm are outbalanced by the risk of medication with presently known antiarrhythmic drugs together with the only modest efficacy of these drugs. Non-pharmacological treatment of atrial fibrillation has drawn increasing interest over the last decade, and especially percutaneous catheter based ablation strategies have been in focus with promising results on the symptomatic level in several series of patients. Different technologies have been in use with very few comparative studies. Most important, no study has been published so far on a consecutive series of patients with atrial fibrillation randomized to either a pharmacological or an ablative strategy. Also important is that the majority of studies have been single-centre based prone to a multitude of potential selection biases.
Hypothesis:
Pulmonary vein isolation by transvenous radiofrequency ablation is superior to present time antiarrhythmic drug therapy with regard to long-term suppression of atrial fibrillation (symptomatic and asymptomatic) as well as to procedure/treatment related side effects.
Purpose:
The present study is designed to test whether catheter based radiofrequency ablation is superior to optimized antiarrhythmic medical therapy in suppressing long-term relapse of symptomatic and/or asymptomatic atrial fibrillation in patients who are not already in chronic pharmaceutical antiarrhythmic therapy. Secondary end points are: mortality, thromboembolic events, hospitalization due to disturbance in heart rhythm, proarrhythmic events, procedure/treatment related side effects, health economics and quality of life. Comparison will be made after two years follow-up and a register follow-up will take place after additional 3 years (a total of at least five years of follow-up).
Consecutive patients fulfilling the inclusion criteria will be informed about the study by a study-responsible electrophysiologist or his/her substitute. After informed consent the patient will be randomized to either antiarrhythmic drug treatment or to catheter ablation. All patients undergo transthoracic echocardiography before randomization.
A register of all patients informed about (i.e. fulfilling the inclusion criteria) but for one or more reasons not included in the study will be established.
Primary endpoint:
Atrial fibrillation burden (see below), symptomatic and asymptomatic combined. Atrial fibrillation burden will be calculated from one-week Holter monitoring at 3, 6, 12, 18 and 24 months, respectively, after treatment (first RF-procedure or AAD-initiation).
Secondary endpoints:
- Mortality
- Complications (including thromboembolic events, major bleeding episodes, pro-arrhythmic events, and treatment related side effects)
- QOL
- Health economics (including number of DC-conversions, cardiovascular hospitalizations (type, length and number of antiarrhythmic drugs))
- Chronic atrial fibrillation (constant atrial fibrillation during one-week Holter monitoring at 24 months follow-up, together with atrial fibrillation during the immediately foregoing 8 weeks)
- Time to first recurrence (after 3 months blanking period)
- Left ventricular systolic function (transthoracic echo)
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Aarhus, Denmark, 8200
- Department of cardiology
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients ≤ 70 years of age
- Paroxysmal atrial fibrillation patients who are considered as being candidates for antiarrhythmic drug therapy initiation
- Patients who have had at least two episodes of symptomatic paroxysmal atrial fibrillation in the foregoing 6 months can be included. The atrial fibrillation episodes may be persistent (need DC- or AAD-conversion) with a duration of less than 7 days.
Exclusion Criteria:
- Previous or ongoing chronic treatment with class IC or class III antiarrhythmic drugs
- Intolerance/contraindication to class IC and class III antiarrhythmic drugs (i.e. intolerance/contraindication to only one of the two groups is not excluding the patient)
- Previous atrial fibrillation ablation
- Severely increased left atrial size
- Left ventricular ejection fraction below 0.40 (during sinus rhythm or atrial fibrillation with RR-intervals above 600 ms) or "eye-balled" reduction of systolic function to less than "moderately decreased".
- Contraindication to anticoagulation treatment with vitamin K antagonists
- Expected surgery for structural heart disease within the follow-up period Significant mitral valve disease
- New York Heart Association (NYHA) III-IV
- Planned pregnancy within the follow-up period
- Secondary atrial fibrillation (e.g. post-surgery, infections, hyperthyroidism)
- Age < 18 years
- Patient does not want to participate.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 2
|
Pulmonary vein isolation
|
Active Comparator: 1
Antiarrythmic drug treatment
|
Pulmonary vein isolation
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Atrial fibrillation burden
Time Frame: Two years
|
Two years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Quality of life
Time Frame: 2 years
|
2 years
|
mortality
Time Frame: 2 years
|
2 years
|
complications to treatment
Time Frame: 2 years
|
2 years
|
Health economics
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jens Cosedis Nielsen, MD, DMSc, Aarhus University Hospital Skejby
Publications and helpful links
General Publications
- Nielsen JC, Johannessen A, Raatikainen P, Hindricks G, Walfridsson H, Pehrson SM, Englund A, Hartikainen J, Mortensen LS, Hansen PS; MANTRA-PAF Investigators. Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation: 5-year outcome in a randomised clinical trial. Heart. 2017 Mar;103(5):368-376. doi: 10.1136/heartjnl-2016-309781. Epub 2016 Aug 26.
- Walfridsson H, Walfridsson U, Nielsen JC, Johannessen A, Raatikainen P, Janzon M, Levin LA, Aronsson M, Hindricks G, Kongstad O, Pehrson S, Englund A, Hartikainen J, Mortensen LS, Hansen PS. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial. Europace. 2015 Feb;17(2):215-21. doi: 10.1093/europace/euu342. Epub 2015 Jan 6.
- Aronsson M, Walfridsson H, Janzon M, Walfridsson U, Nielsen JC, Hansen PS, Johannessen A, Raatikainen P, Hindricks G, Kongstad O, Pehrson S, Englund A, Hartikainen J, Mortensen LS, Levin LA. The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from a MANTRA-PAF substudy. Europace. 2015 Jan;17(1):48-55. doi: 10.1093/europace/euu188. Epub 2014 Oct 23.
- Cosedis Nielsen J, Johannessen A, Raatikainen P, Hindricks G, Walfridsson H, Kongstad O, Pehrson S, Englund A, Hartikainen J, Mortensen LS, Hansen PS. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med. 2012 Oct 25;367(17):1587-95. doi: 10.1056/NEJMoa1113566.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- sks2005psh01
- NCT00133211
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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