Trial Outcomes & Findings for REVOLUTION (WFCC-133) - Treatment of Paroxysmal Atrial Fibrillation (NCT NCT01353586)

Last Updated: 2017-06-06

Results Overview

The primary safety endpoint is the incidence of early onset primary adverse events within 7 days of the mapping and ablation procedure. Primary adverse events include pericardial effusion requiring intervention, atrial perforation, pericarditis requiring intervention, cardiac tamponade, pneumothorax, death, pulmonary edema, diaphragmatic paralysis, heart block, stroke / cerebrovascular accident (CVA), hospitalization (initial and prolonged), thromboembolism, myocardial infarction (MI), transient ischemic attack (TIA), and vascular access complications. In addition, pulmonary vein stenosis and atrio-esophageal fistula that occurs greater than one week (7 days) post-procedure are deemed primary adverse event.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

186 participants

Primary outcome timeframe

Any of above events occurring within 7 days post-procedure (also including the incidence of pulmonary vein stenosis and atrio-esophageal fistula occurring > 7 days and up to one year post-procedure)

Results posted on

2017-06-06

Participant Flow

A total of 186 eligible subjects enrolled in this study across 8 sites in Europe. The first was enrolled on March 14, 2011 and was treated on March 15, 2011. The last was enrolled on October 16, 2012. The study's last 12 month follow-up visit occurred on September 27, 2013.

The Main Study consisted only of subjects treated with nMARQ ablation system, without a control arm. Later, a Subpopulation Neurological Assessment (SNA) was added to evaluate for potential cerebral micro-emboli and neurological deficits post ablation. The SNA included a comparator control arm of subjects treated with the Navistar® ThermoCool®.

Participant milestones

Participant milestones
Measure	nMARQ™ (Main Study- Single Arm) This group of subjects underwent electrophysiological mapping and radiofrequency ablation with the Biosense Webster nMARQ™ system. The Main Study (167 subjects) consists only of subjects treated with the nMARQ catheter.	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
Overall Study STARTED	167	19
Overall Study Participated in Workflow Phase	20	0
Overall Study Participated in Roll-in Phase	22	0
Overall Study Participated in SNA Substudy	19	19
Overall Study COMPLETED	160	17
Overall Study NOT COMPLETED	7	2

Reasons for withdrawal

Reasons for withdrawal
Measure	nMARQ™ (Main Study- Single Arm) This group of subjects underwent electrophysiological mapping and radiofrequency ablation with the Biosense Webster nMARQ™ system. The Main Study (167 subjects) consists only of subjects treated with the nMARQ catheter.	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
Overall Study Procedure terminated prior to ablation	3	0
Overall Study Never had insertion of study catheter	4	1
Overall Study Neurological exam not done	0	1

Baseline Characteristics

REVOLUTION (WFCC-133) - Treatment of Paroxysmal Atrial Fibrillation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	nMARQ™ (Main Study- Single Arm) n=163 Participants This group of subjects underwent electrophysiological mapping and radiofrequency ablation with the Biosense Webster nMARQ™ system. The Main Study (167 subjects) consists only of subjects treated with the nMARQ catheter.	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) n=17 Participants Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.	Total n=180 Participants Total of all reporting groups
Age, Continuous	58.7 years STANDARD_DEVIATION 10.24 • n=5 Participants	56.5 years STANDARD_DEVIATION 9.86 • n=7 Participants	58.49 years STANDARD_DEVIATION 10.0 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	3 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	112 Participants n=5 Participants	14 Participants n=7 Participants	126 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	110 Participants n=5 Participants	14 Participants n=7 Participants	124 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	53 Participants n=5 Participants	3 Participants n=7 Participants	56 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	110 Participants n=5 Participants	14 Participants n=7 Participants	124 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	53 Participants n=5 Participants	3 Participants n=7 Participants	56 Participants n=5 Participants

PRIMARY outcome

Timeframe: Any of above events occurring within 7 days post-procedure (also including the incidence of pulmonary vein stenosis and atrio-esophageal fistula occurring > 7 days and up to one year post-procedure)

Population: Safety Population as defined above

Outcome measures

Outcome measures
Measure	nMARQ™ (Main Study- Single Arm) n=163 Participants The Main Study group consists of subjects who were treated with the Biosense Webster nMARQ™ system. This group is single-arm and does not include the SNA substudy population (no comparator group).	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
The Incidence of Early Onset Primary Adverse Events	5.5 percentage of participants Interval 2.6 to 10.2	—

PRIMARY outcome

Timeframe: Evaluated from Day 91 to Day 240

Population: Effectiveness cohort: This population excludes those subjects who never underwent insertion of study catheter, those who terminated procedure prior to ablation, and those who were enrolled during the Workflow phase (20 subjects) and Roll-in phase (22 subjects). This analysis also excludes two subjects who withdrew consent post ablation.

The primary effectiveness endpoint is freedom from documented symptomatic atrial fibrillation based on electrocardiographic data through 8 months post ablation.

Outcome measures

Outcome measures
Measure	nMARQ™ (Main Study- Single Arm) n=116 Participants The Main Study group consists of subjects who were treated with the Biosense Webster nMARQ™ system. This group is single-arm and does not include the SNA substudy population (no comparator group).	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
Incidence of Freedom From Documented Symptomatic Atrial Fibrillation	71.6 percentage of participants Interval 62.4 to 79.5	—

SECONDARY outcome

Timeframe: 12 months post study procedure

Population: Safety population

This secondary safety endpoint includes non-primary serious adverse events within 7 days post-procedure and serious adverse events from 7 days to 12 months post-procedure.

Outcome measures

Outcome measures
Measure	nMARQ™ (Main Study- Single Arm) n=163 Participants The Main Study group consists of subjects who were treated with the Biosense Webster nMARQ™ system. This group is single-arm and does not include the SNA substudy population (no comparator group).	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
Incidence of Non-Primary Serious Adverse Events (SAEs) up to 12 Months Non-primary serious AEs within 7 days	0.6 percentage of participants	—
Incidence of Non-Primary Serious Adverse Events (SAEs) up to 12 Months Serious adverse events from 7 days to 12 months	15.3 percentage of participants	—

SECONDARY outcome

Timeframe: Three months after index ablation

Population: Subjects in safety analysis group who also had CT/MRI PV scan available at the 3-month post-ablation interval (144 of 160 subjects)

Incidence of narrowing of PV and stenosis at 3 months post ablation, for subjects with available CT/MRA scans at 3 months. PV Stenosis is defined as 70% or more PV diameter reduction.

Outcome measures

Outcome measures
Measure	nMARQ™ (Main Study- Single Arm) n=144 Participants The Main Study group consists of subjects who were treated with the Biosense Webster nMARQ™ system. This group is single-arm and does not include the SNA substudy population (no comparator group).	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
Assessment of Pulmonary Vein (PV) Narrowing and Stenosis at 3 Months After Index Ablation 0-20% Reduction of PV Diameter	47.2 percentage of participants with CT/MRI	—
Assessment of Pulmonary Vein (PV) Narrowing and Stenosis at 3 Months After Index Ablation 21- 50% Reduction of PV Diameter (Mild)	51.4 percentage of participants with CT/MRI	—
Assessment of Pulmonary Vein (PV) Narrowing and Stenosis at 3 Months After Index Ablation 51-70% Reduction of PV Diameter (Moderate)	1.4 percentage of participants with CT/MRI	—
Assessment of Pulmonary Vein (PV) Narrowing and Stenosis at 3 Months After Index Ablation > 70% Reduction of PV Diameter (Severe)	0.0 percentage of participants with CT/MRI	—

SECONDARY outcome

Timeframe: From 7 days to 12 months post study procedure

Population: Safety population excluding one subject without source document at site

This secondary outcome describes the acute effectiveness, which is defined as pulmonary vein isolation (PVI) documented by confirmed entrance block (with or without the use of a focal catheter).

Outcome measures

Outcome measures
Measure	nMARQ™ (Main Study- Single Arm) n=117 Participants The Main Study group consists of subjects who were treated with the Biosense Webster nMARQ™ system. This group is single-arm and does not include the SNA substudy population (no comparator group).	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
Incidence of Completion of Ablation Procedure	100 percentage of participants Interval 96.9 to 100.0	—

SECONDARY outcome

Timeframe: 6 and12 months post study procedure

Population: This analysis population is the effectiveness cohort, excluding 2 subjects who withdrew consent prior to Day 91. The effectiveness cohort includes those who received treatment with the investigational device; but does not include 20 workflow and 22 roll-in subjects.

This endpoint is defined as the absence of documented symptomatic PAF recurrence through 6 months and 12 months post index ablation procedure.

Outcome measures

Outcome measures
Measure	nMARQ™ (Main Study- Single Arm) n=116 Participants The Main Study group consists of subjects who were treated with the Biosense Webster nMARQ™ system. This group is single-arm and does not include the SNA substudy population (no comparator group).	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
Absence of Documented Symptomatic PAF Through 6 Months and 12 Months Post Procedure 6 months post ablation	73.3 percentage of participants Interval 64.3 to 81.1	—
Absence of Documented Symptomatic PAF Through 6 Months and 12 Months Post Procedure 12 months post ablation	60.3 percentage of participants Interval 50.8 to 69.3	—

SECONDARY outcome

Timeframe: 48 hours post-ablation

Population: Neurological assessment subpopulation. This population includes 19 subjects from the nMARQ main study and 17 subjects from the Thermocool control group.

Evaluation of post-ablation generation incidence of asymptomatic cerebral microembolic lesions post ablation, as documented by MRI. All microembolic lesions reported in this study are asymptomatic.

Outcome measures

Outcome measures
Measure	nMARQ™ (Main Study- Single Arm) n=19 Participants The Main Study group consists of subjects who were treated with the Biosense Webster nMARQ™ system. This group is single-arm and does not include the SNA substudy population (no comparator group).	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) n=17 Participants Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
Subpopulation Neurological Assessments (SNA) Endpoint 1 - Incidence of Cerebral Embolic (ACE) Lesions Post Ablation	21.1 percentage of subjects with ACE Lesion	5.9 percentage of subjects with ACE Lesion

SECONDARY outcome

Timeframe: 48 hours post-ablation

Population: Neurological assessment subpopulation. This population includes 19 subjects from the nMARQ main study and 17 subjects from the Thermocool control group.

All SNA subjects were to be evaluated by expert neurologists for existing neurological deficits prior to ablation procedure. After procedure, those subjects were also to be assessed for new neurological deficits.

Outcome measures

Outcome measures
Measure	nMARQ™ (Main Study- Single Arm) n=19 Participants The Main Study group consists of subjects who were treated with the Biosense Webster nMARQ™ system. This group is single-arm and does not include the SNA substudy population (no comparator group).	NAVISTAR® THERMOCOOL® (SNA Subpopulation Only) n=17 Participants Version 3.0 of the Clinical Investigation Plan added a Subpopulation Neurological Assessments (SNA) designed to evaluate post-ablation generation of cerebral microemboli and associated neurological deficits. These assessments were done in a prospective, non-randomized manner, comparing subjects treated with the nMARQ system against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. Per study design, the data from the NAVISTAR® THERMOCOOL® subpopulation would be used for SNA analysis only. The data in this column are presented for transparency; but cannot be compared statistically against the data from the Main Study group.
Subpopulation Neurological Assessments (SNA) Endpoint 2 - Incidence of New Neurological Findings Post Ablation	0 percentage of participants	0 percentage of participants

Adverse Events

nMARQ™ System (Main Study)

Serious events: 31 serious events

Other events: 65 other events

Deaths: 0 deaths

NAVISTAR® THERMOCOOL® (SNA Subpopulation Only)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Kendra McInnis, Manager, Clinical Operations

Biosense Webster, Inc

Phone: 909-839-7284

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee There IS an agreement between the Principal Investigator (PI)/Institution and the Sponsor (or its agents) that restricts the PI's rights to discuss, present or publish trial results after the trial is completed. Please contact Biosense Webster, Inc. for additional information.
Publication restrictions are in place

Restriction type: OTHER