Clinical trial NCT01298986: Atrial Fibrillation Ablation The Hybrid Approach Versus Traditional Management
Official title: Atrial Fibrillation Ablation The Hybrid Approach Versus Traditional Management
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Ablation of Atrial Fibrillation
Keywords: atrial fibrillation ablation procedures
Lead sponsor: Inova Health Care Services
Sponsor class: OTHER
First posted: 2011-02-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rationale: To determine the most beneficial ablation methodology for individual patients with paroxysmal or persistent atrial fibrillation (defined by the Heart Rhythm Society) as surgeons and electrophysiologists work together on a convergent procedure (hybrid) to place the epicardial and endocardial ablation lines.

Objectives: Catheter and surgical ablation are being offered today to patients with drug refractory and symptomatic atrial fibrillation. This study is designed to assess the most efficient ablation approach in patients with paroxysmal and persistent atrial fibrillation. In patients with left atrium size of less than 5.0 cm, a Hybrid approach (pulmonary vein isolation performed surgically will be combined with right and left atrial flutter lines performed using a transcatheter approach) will be compared to percutaneous catheter ablation to isolate the pulmonary veins and apply the left and right atrial flutter lines with removal of LA appendage. In the group of patients with left atrial size 5.0-6.0 cm the Hybrid approach is going to be compared to the minimally invasive Cox-Maze III procedure.

Our hypotheses with regard to the rate of return to sinus rhythm off antiarrhythmic drugs at 6 months will demonstrate that the Hybrid approach is going to be a: superior to percutaneous catheter ablation in the less than 5 cm left atrial group and b: non-inferior when compared to the Cox-Maze III procedure in the 5-6 cm left atrial cm group.

We hypothesize that the safety of all procedures will show no differences and that there will be no differences in clinical complications between groups.

Detailed description: Study Type: This is an experimental study in which patients who present with either paroxysmal or persistent atrial fibrillation will be randomized based on their left atrial size (≤ 5.0 or \> 5.0 but \< 6.1 cm) to receive a hybrid ablation approach vs percutaneous catheter where in both procedures ablation will include pulmonary vein isolation with a left and right atrial flutter line for patients with a left atrium ≤ 5.0 cm. and hybrid approach will be compared to the Cox Maze III procedure for patients with a left atrium \> 5.0 \< 6.1 cm .

Study Design: One hundred and fifty two patients (n=152) with persistent or paroxysmal atrial fibrillation who present for surgical or catheter ablation intervention are to be enrolled. The study will take place at the Inova Heart and Vascular Institute in Falls Church, VA in the specially designed hybrid surgical suite in the cardiovascular operating area. We expect enrollment to take (two years study duration). Patients will be included if they present for ablation with paroxysmal or persistent atrial fibrillation as defined by the Heart Rhythm Society and their left atrium is \< 6.1 cm (volume). Patients will be excluded if they present with long standing persistent atrial fibrillation as defined by the Heart Rhythm Society, require other cardiac surgery, are unable to take anticoagulation or require prescribed anti arrhythmic medication for reason other than atrial fibrillation, have a left atrium measuring greater than 6.0 cm (volume),have had previous catheter ablation for atrial fibrillation (Do not exclude for prior AVNRT) or a pacemaker, are less than 18 years of age, are unable or unwilling to be followed according to set protocol to include implantation of a heart monitor 6 weeks prior to their ablation procedure.

Study Methodology: This is an experimental study in which patients who present with either paroxysmal or persistent atrial fibrillation will be randomized based on their left atrial size.

For patients with a left atrium size of less than 5.0 cm, a Hybrid approach (pulmonary vein isolation performed surgically will be combined with right and left atrial flutter lines performed using a transcatheter approach) will be compared to percutaneous catheter ablation to isolate the pulmonary veins and apply the left and right atrial flutter lines. In the group of patients with left atrial size of 5.0-6.0 cm the Hybrid approach is going to be compared to the minimally invasive Cox-Maze III procedure (Figure 1). Each patient regardless of procedure will have their left atrial appendage closed. All patients will receive an internal event monitor (Reveal XT) which will be placed 6 weeks before their procedure to establish atrial fibrillation burden. All patients will also be given a health related quality of life and a symptom frequency and severity tool to fill out prior to their ablation and at 3 and 6 months post ablation.

The primary outcome will be the rate of return to sinus rhythm as defined by the Heart Rhythm Society Guidelines (sinus rhythm maintained off anti arrhythmic medications and any monitored atrial arrhythmia greater than 30 seconds will be considered a recurrence) at 6 months and atrial fibrillation burden

The secondary outcomes will include:

Number and type of procedural complications Number of embolic strokes The number of major bleeding events as defined by the need to receive a transfusion for the amount of blood lost and or hemorrhagic stroke while receiving anticoagulation therapy.

Reported improvement in patients' self reported health related quality of life and their symptom frequency and severity at 3 and 6 months

Statistical Methodology: Since this is a proof of concept study without any prior literature to obtain margins, we used the current rate of return to sinus rhythm as our margins to determine sample size. This is fully explained in section 4.2. Based on these calculations, 152 patients will be randomized as described above. Descriptive statistics will be used to characterize the patient population. T-tests and ANOVAs will be used to look for differences between groups within the continuous data. Chi square, Fisher's Exact test and/or McNemar's Test will be used to look for differences among categorical variables. For all analyses, a two-sided p value \<0.05 will be used to determine significance.

To analyze the primary objective, the percentage of patients in each group who return to normal sinus rhythm will be calculated. Chi square analysis, or logistic regression if covariates are required, will be used to test for differences in the odds of returning to normal sinus rhythm between the treatment groups in both arms of the study. Chi square and/or logistic regression will also be used to assess the secondary aim regarding complications between the treatment groups. For the left atrial size \> 5.0 but \< 6.1 cm arm of the study, testing for non-inferiority of complication rates will be conducted using the treatment effect and 95% confidence intervals. These will be compared against the 10% non-inferiority margins, to assess whether the treatment effect and 95% confidence interval fall entirely within the margins. Lastly, repeated measures analysis of variance (ANOVA) will be conducted to examine the secondary aim regarding change in health-related quality of life by treatment groups.

Eligibility criteria: Inclusion Criteria:

1. Patients will be included if they present for ablation with paroxysmal or persistent atrial fibrillation as defined by the Heart Rhythm Society and their left atrium is \< 6.1 cm (volume)
2. Patients must be symptomatic with their AF as noted by their inability to perform their daily activities due to shortness of breath, fatigue, palpitations or other debilitating symptoms
3. Paroxysmal atrial fibrillation is defined as atrial fibrillation that resolves on its own within 7 days of onset
4. Persistent atrial fibrillation is defined as atrial fibrillation that does not resolve on its own and requires medical intervention to include medication therapy and/or electric cardioversion

Exclusion Criteria:

1. Patients will be excluded if they present with long standing persistent atrial fibrillation as defined by the Heart Rhythm Society
2. All patients with MV +2 mitral regurgitation will be excluded
3. Require other cardiac surgery procedures will be excluded
4. Are unable to take anticoagulation
5. Are unable to take any prescribed anti arrhythmic medication
6. Have a left atrium measuring greater than 6.0 cm (volume)
7. Have had previous catheter ablation for atrial fibrillation
8. Have had previous pace maker implantation
9. Are less than 18 years of age
10. Do not speak English and no translation can be provided
11. Are unable or unwilling to be followed according to set protocol to include obtaining an internally heart monitor 6 weeks prior to their ablation procedure

Primary outcomes:
measure: Return to sinus rhythm rate
timeFrame: 2-3 years
Secondary outcomes:
measure: Post procedure morbidities
timeFrame: up to 6 months post procedure
Other outcomes:
Locations:
Study officials:
affiliation: Inova Fairfax Hospital
name: Niv Ad, MD
role: PRINCIPAL_INVESTIGATOR
References: