Clinical Trial Details

Overview

Research Study Summary

nMARQ™ Pulmonary Vein Isolation System for the Treatment of Paroxysmal Atrial Fibrillation reMARQable

Purpose

Catheter ablation has been used for over a decade to treat AF patients to achieve PVI. Significant catheter design improvements (e.g., irrigated encircling catheters) focus upon improving physicians’ abilities to achieve finite entrance block following PVI. The primary intent of this study is to generate clear and sufficient safety and effectiveness data for PMA approval on the use of both the nMARQ™ Circular- and nMARQ™ Crescent-shaped Irrigated RF ablation Catheters, in achieving PVI, when used in conjunction with the nMARQ™ Multi-channel RF Generator.

The 2012 HRS/EHRA/ECAS Expert Consensus Statement points out that the “concordance of the clinical trial data revealing the superiority of ablation over drugs for symptomatic paroxysmal AF recurrences” and the difficulties of subject enrollment and study management in conducting drug versus ablation studies, have led to widespread support of more relevant study designs, which compare a “novel device” to one that is already approved for use.19 The design of this protocol, a comparison of the nMARQ™ Catheter System [nMARQ™] versus the already marketed THERMOCOOL® Navigational Family of catheters [TC], reflects the same approach as supported by global experts for industry-sponsored clinical trials that assess new technology for catheter ablation.

Anticoagulation leading up to, during, and following ablation treatment, can influence subject outcomes, particularly stroke. Therefore, this protocol will require a specific regimen for anticoagulation (Section 9.3.1) throughout the study period based on current recommendations and standards of practice. These requirements will include (i) a wafarin treatment regimen; (ii) a need to keep the pre-ablation International Normalized Ratio (INR) >2.0; (iii) appropriate use of heparin during the procedure to maintain an Activated Clotting Time (ACT) ≥325 seconds; (iv) giving heightened attention to continuous flushing of sheaths; and, (v) maintaining a vigilant awareness of risks of air embolism.

Efforts to achieve PVI with current catheter designs may present technical challenges for some operators in creating long contiguous ablation lines. Currently available RF catheters are used to ablate single targets (areas of potential) at a time in patients with AF; however, long contiguous lesions, which are formed by making multiple, consecutive single lesions, are often required to achieve PVI. Placement of additional RF lesions in the left and right atria has been investigated by a number of research centers34, 31, 53, 54 (e.g., a line of block between the left inferior PV and the mitral annulus); however, there is no consensus on the necessity, quantity, or anatomical placement of these extra RF lesions. Given that the nMARQ™ irrigated RF ablation catheters were designed specifically to create long continuous lesions, this trial will evaluate the relative ability of physicians to achieve PVI with confirmed entrance block.

The primary purpose of this randomized, controlled study is to establish the overall safety and effectiveness of the nMARQ™ PVI System for the radiofrequency catheter ablation treatment of symptomatic, drug refractory, paroxysmal atrial fibrillation. A key focus within the full safety assessment of the nMARQ™ System will be the frequency of occurrence, clinical sequelae, and duration of effect of cerebroembolic lesions associated with stroke, TIA, or silent microemboli. Other key measurements will address the duration and manner in which treated subjects remain asymptomatic.

Previous Experience with nMARQ™ PVI Ablation System Bench and Animal Studies Bench and animal testing has been performed using the nMARQ™ Circular and Crescent Irrigated Catheters and the nMARQ™ Multi-channel RF Generator. Please refer to the Report of Prior Investigations for detailed summaries of the test protocols and corresponding reports.

Circular Ablation Catheter and Crescent Ablation Catheter for the Radiofrequency Ablation of Atrial Fibrillation (AFCC-126) Feasibility Study A total of 9 subjects were enrolled in this study from December 2009 through July 2010. One subject was excluded (after signing the informed consent form) for not meeting the inclusion criteria to have a documented AF episode in the 6 months prior to enrollment. Therefore, 8 subjects are considered evaluable, 5 PAF subjects (62.5%, 5/8) and 3 Persistent AF subjects (37.5%, 3/8). The mean age at date of procedure was 59.9 ± 7.2 years and ranged from 26.7 to 70.9. Three (3) of the enrolled subjects (33.3%) were female and six (6) (66.7%) were male.

Excluding the protocol-specific arrhythmias, the most prevalent medical condition reported at baseline was atrial flutter (55.6%) followed by hypertension (33.3%).

No subject deaths, early-onset primary AEs, serious adverse events or device or procedure related adverse events were reported. Four non-serious adverse events were reported; all were unrelated to the device or procedure. Two (2) subjects required a repeat ablation procedure, both >6 months post index ablation.

No pulmonary vein stenosis (≥70% narrowing) was reported for any of the subjects treated with the investigational catheters.

All investigators responded that the catheter/tissue contact interface was ‘excellent.’ On a scale of 1 to 5, the mean rating for effectiveness of mapping and ablation for both catheters was 4 or greater. Acute success, defined as isolation of a targeted pulmonary vein using the nMARQ™ Circular or nMARQ™ Crescent Irrigated Catheter, was greater than 60% for each targeted vein (LIPV: 62.5%, LSPV: 75%, RIPV: 62.5%, RSPV: 75%).

The Circular and Crescent Irrigated Catheters, when used with the RF Generator System for the treatment of paroxysmal and persistent atrial fibrillation, performed as expected.

REVOLUTION clinical study The purpose of this study was to assess the safety and effectiveness of the nMARQ™ Circular and Crescent Mapping & Ablation catheters and the workflow of the Multi-Electrode Irrigated PV Isolation System when used for the treatment of Paroxysmal AF (PAF).

Since March 14, 2011 through July 12, 2012 (date of interim dataset compilation [REVOLUTION Interim Report 20OCT2012], enrollment ongoing), among 8 investigational sites, 149 subjects have undergone a pulmonary vein isolation (PVI) study procedure using the Biosense Webster Circular and Crescent Mapping and Ablation Catheters and Multi-Channel RF Generator. The study began with a Workflow Phase, which included the first 20 subjects enrolled. Following completion of the Workflow Phase, all subsequent subjects enrolled were included in the Main Study, which began with a Roll-in Phase (first three subjects per site).

Although 158 subjects were enrolled, three (3) were excluded and an additional 12 have missing data and were not counted in the evaluable population of the data set. There were also 6 control subjects (treated with the NAVISTAR® THERMOCOOL® catheter) who were part of the SNA subpopulation and are not part of the evaluable nMARQ™ population. Safety outcomes for the remaining 137 nMARQ™ subjects that comprise the Evaluable and Safety Cohorts are presented in the study interim report; additionally, baseline and available follow-up data and acute effectiveness results are also presented.

Statistically significant differences were not found for baseline gender or age by site (comparison among sites using Fisher’s Exact Test for categorical variables and analysis of variance for age). The primary safety endpoint was the incidence of early-onset (within seven [7] days of the index mapping and ablation procedure) primary adverse events (AEs). Among the 137 Evaluable Cohort Subjects (also the Safety Cohort because no subjects had been discontinued) plus one subject who had the study device inserted but the procedure stopped before ablation, eight (8) early-onset primary AEs occurred. Thirty-eight (38) serious AEs also occurred. Pulmonary vein (PV) stenosis was another safety outcome evaluated in this study. Of the 94 subjects with available 3-month CT/MRA scans, none had protocol-defined PV stenosis of ≥70% diameter reduction of the pulmonary vein from baseline. Fifty subjects (50/94, 53.2%) had no (0-20% narrowing) PV diameter reduction from baseline and the rest had a mild (>20 50% narrowing) reduction in PV diameter (44/94, 46.8%). Effectiveness outcomes evaluated for the interim report included acute effectiveness (confirmation of entrance block), repeat ablation, quality of life, and recurrence of documented symptomatic AF at 8 months. Confirmation of entrance block was achieved in 128/130 (98.5%) of the subjects in the Evaluable Cohort, with 23/137 (16.8%) requiring a repeat ablation. Quality of life measures at 3-, 6-, and 12-months post-ablation indicated perceived improvement in heart function impact on daily life. For the Effectiveness Cohort, the probability of freedom from documented symptomatic AF through 8 months post-ablation (primary effectiveness endpoint in this protocol) was estimated to be 69.5%.

Use of the Circular and Crescent Mapping & Ablation catheters and the Multi channel RF Generator, and the workflow of the Multi-Electrode Irrigated PV Isolation System and THERMOCOOL® catheter as part of a toolkit, raised no unanticipated safety concerns and demonstrated a favorable safety adverse event profile. The number of early-onset primary AEs was low. No strokes, deaths, or unanticipated adverse device effects were reported and quality of life and effectiveness measures had an acceptable profile. Since the study is ongoing, continued subject enrollment, evaluation, and follow-up will be conducted, with the expectation that the safety profile will be confirmed and the effectiveness profile will be more fully characterized.

To Learn more

CW ID: 216038
Date Last Changed: June 13, 2016

Clinical Trial Snapshot

Gender
Both Male and Female
Age
18 and up
Overall Status
Recruiting
Lead Sponsor
Biosense Webster, In
Duration
12 Months
Facility Type
N/A

Eligibility

Inclusion Criteria:
Candidates must meet ALL of the following criteria:
  • Patients with symptomatic paroxysmal AF who have had at least one AF episode documented within one (1) year prior to enrollment. Documentation may include ECG, transtelephonic monitor (TTM), Holter monitor (HM), or telemetry strip.
  • Patients who have failed at least one antiarrhythmic drug (AAD; class I or III, or AV nodal blocking agents such as beta blockers and calcium channel blockers) as evidenced by recurrent symptomatic AF, or intolerance to the AAD.
  • Age 18 years or older.
  • Signed Patient Informed Consent Form (ICF).
  • Able and willing to comply with all pre-, post-, and follow-up testing and requirements.
Exclusion Criteria:
Candidates will be excluded if ANY of the following criteria apply:
  • AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause.
  • Previous ablation for atrial fibrillation.
  • Patients on amiodarone at any time during the past 3 months prior to enrollment.
  • AF episodes lasting > 7 days..
  • Any cardiac surgery within the past 60 days (2 months) or valvular cardiac surgical procedure (i.e., ventriculotomy, atriotomy, and valve repair or replacement and presence of a prosthetic valve).
  • CABG procedure within the last 180 days (6 months).
  • Awaiting cardiac transplantation or other cardiac surgery within the next 365 days (12 months).
  • Documented left atrial thrombus on imaging.
  • History of a documented thromboembolic event within the past one (1) year.
  • Diagnosed atrial myxoma.
  • Presence of implanted ICD.
  • Significant pulmonary disease, (e.g., restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory system that produces chronic symptoms.
  • Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study.
  • Women who are pregnant (as evidenced by pregnancy test if subject is of child-bearing age and potential) or breast feeding.
  • Acute illness or active systemic infection or sepsis.
  • Unstable angina.
  • Myocardial infarction within the previous 60 days (2 months).
  • Left ventricular ejection fraction <40%.
  • History of blood clotting or bleeding abnormalities.
  • Contraindication to anticoagulation (i.e., heparin, dabigatran, Vitamin K Antagonists such as warfarin).
  • Life expectancy less than 365 days (12 months).
  • Enrollment in an investigational study evaluating another device or drug.
  • Uncontrolled heart Failure or NYHA Class III or IV heart failure.
  • Presence of intramural thrombus, tumor or other abnormality that precludes catheter introduction or manipulation.
  • Presence of a condition that precludes vascular access.
  • Left atrial size >50 mm.

More Info

Study Objectives
Primary Study Objectives
  • To demonstrate the safety of the nMARQ (Test) Group compared to the TC (Control) Group based on difference in proportion of early-onset (within 7 days of ablation procedure) primary adverse events, using a non-inferiority margin of 10% for subjects with symptomatic PAF.
  • To demonstrate the effectiveness of the nMARQ (Test) Group compared to the TC (Control) Group based on difference in proportion of freedom from documented, symptomatic AF/AT/AFL through 12 months post ablation follow-up using a non-inferiority margin of 15% for subjects with symptomatic PAF. Secondary Study Objective: Subpopulation Neurological Assessment (SNA) To evaluate, within a subset of the Main Study PAF population, the comparative incidence of pre- and post-ablation symptomatic and asymptomatic cerebral emboli, as determined by MRI evaluations. The presence of emboli-associated neurological deficits will also be evaluated, using the National Institute of Health Stroke Scale (NIHSS), the Montreal Cognitive Assessment (MoCA), modified Rankin Scale (mRS) and general neurological assessments.

Contact

Feather Wafford, Baptist Health Lexington Research Regulatory Coordinator
Baptist Health Clinical Research Center & Lexington Cardiac Research Foundation
1740 Nicholasville Rd
Lexington, KY 40503
Phone: 859-260-6066
Fax: 859-260-4151

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