STOP Persistent AF

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03012841
• Collaborator: (none)
• Enrollment: 186
• Locations: 25
• Arm: 1
• Actual Duration (Months): 29.4
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To demonstrate safety and effectiveness of the Arctic Front Advance™ and Freezor MAX® Cardiac CryoAblation Catheters for the treatment of drug refractory recurrent symptomatic persistent atrial fibrillation (AF).

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Device: Arctic Front Advance Cardiac CryoAblation Catheter	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 186 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Arctic Front Advance Cardiac CryoAblation Catheter and Freezor MAX Cardiac CryoAblation CatheterArctic Front Advance Cardiac CryoAblation Catheter and Freezor MAX Cardiac CryoAblation Catheter
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: STOP Persistent AF
• Actual Study Start Date: Mar 2, 2017
• Actual Primary Completion Date: Aug 13, 2019
• Actual Study Completion Date: Aug 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Subjects enrolled and treated with Arctic Front Advance Cardiac CryoAblation Catheter	Device: Arctic Front Advance Cardiac CryoAblation Catheter; Cryoablation; Other Names: Freezor MAX Cardiac CryoAblation Catheter

Outcome Measures

Primary Outcome Measures

1. Percent of Subjects Free From Treatment Failure at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure. [12 Months]

   Treatment failure is defined as any of the following components: Acute procedural failure Documented AF/atrial tachycardia (AT)/atrial flutter (AFL) after the 90 day blanking period A reablation for the treatment of recurrent AF/AT/AFL after the 90 day blanking period Class I or III antiarrhythmic drug (AAD) dose increase from the historic maximum ineffective dose (prior to the ablation procedure) or initiation of a new Class I or III AAD after the 90 day blanking period. Ablation using radiofrequency (RF) in the left atrium Blanking period is defined as the first 90 days after the index ablation procedure. Acute procedural failure is defined as: Inability to isolate all accessible targeted pulmonary veins (minimally assessed for entrance block and, where assessable, exit block) during the index procedure Left atrial non-PVI ablations including but not limited to, ablation of linear lesions complex fractionated electrograms or non-PV triggers

2. Percent of Subjects Free From a Primary Safety Event at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure. [12 months]

   A primary safety event is defined as a serious procedure-related or serious system-related adverse event including the following: Transient ischemic attack (within 7 days of ablation procedure) Cerebrovascular accident (within 7 days of ablation procedure) Major bleeding that requires transfusion (within 7 days of ablation procedure) Cardiac perforation, tamponade or pericardial effusion (within 7 days of ablation procedure) Pulmonary vein stenosis (> 75% reduction within 12-months of ablation procedure) Myocardial infarction (within 7 days of ablation procedure) Phrenic nerve injury (unresolved at 12-months) Atrio-esophageal fistula (within 12-months of ablation procedure) Death (within 7 days of ablation procedure)

Secondary Outcome Measures

1. Change in Quality of Life Between Baseline and 12 Months: Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) [Baseline and 12 months]

   Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire completed at baseline and 12 month visits. The AFEQT instrument yields scores from 0 (representing the worst possible debilitation from AF) to 100 (representing no reduction in quality of life from AF).

2. Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Physical Component [Baseline and 12 months]

   Medical Outcome Study Short Form-12 (SF-12) questionnaire completed at baseline and 12 month visits. The SF-12 instrument has two composite scores, one for physical health and one for mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life).

3. Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Mental Component [Baseline and 12 months]

   Medical Outcome Study Short Form-12 (SF-12) questionnaire completed at baseline and 12 month visits. The SF-12 instrument has two composite scores, one for physical health and one for mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documentation of symptomatic persistent AF: Defined as having a continuous episode lasting longer than 7 days but less than 6 months documented by consecutive ECG recordings OR Defined as having a continuous episode lasting longer than 7 days but less than 6 months documented by an ECG recording and one doctor note indicating patient had symptoms consistent with AF

• Failure or intolerance of at least one Class I or III antiarrhythmic drug

• Age 18 or older (or older than 18 if required by local law)

Exclusion Criteria:

• Left atrial diameter > 5.0 cm (anteroposterior)

• Prior left atrial ablation or surgical procedure (including left atrial appendage closures)

• Presence or likely implant of a permanent pacemaker, biventricular pacemaker, loop recorder, or any type of implantable cardiac defibrillator (with or without biventricular pacing function) within 12 months

• Presence of any pulmonary vein stents

• Presence of any pre-existing pulmonary vein stenosis

• Pre-existing hemidiaphragmatic paralysis

• Presence of any cardiac valve prosthesis

• +3 and +4 mitral valve regurgitation or stenosis

• Any cardiac surgery, myocardial infarction, percutaneous coronary intervention (PCI) / percutaneous transluminal coronary angioplasty (PTCA) or coronary artery stenting which occurred during the 3 month interval preceding the consent date

• Unstable angina

• New York Heart Association (NYHA) Class III or IV congestive heart failure and/or documented left ventricular ejection fraction (LVEF) less than or equal to 35% measure by acceptable cardiac testing (e.g. Transthoracic echocardiogram (TTE))

• Primary pulmonary hypertension

• Rheumatic heart disease

• Thrombocytosis, thrombocytopenia

• Any condition contraindicating chronic anticoagulation

• Active systemic infection

• Hypertrophic cardiomyopathy

• Cryoglobulinemia

• Uncontrolled hyperthyroidism

• Any cerebral ischemic event (strokes or transient ischemic attacks (TIAs)) which occurred during the 6 month interval preceding the consent date

• Any woman known to be pregnant or breastfeeding, or any woman of child bearing potential who is not on a reliable form of birth regulation method or abstinence

• Life expectancy less than one year

• Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of the study not pre-approved by Medtronic

• Known allergies or hypersensitivities to adhesives

• Known drug or alcohol dependency

• Unwilling or unable to comply fully with study procedures and follow-up

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner-University Medical Center Phoenix	Phoenix	Arizona	United States	85006
2	Colorado Heart and Vascular	Lakewood	Colorado	United States	80228
3	Medical Center of the Rockies	Loveland	Colorado	United States	80538
4	Cardiac Arrhythmia Service	Boca Raton	Florida	United States	33432
5	Saint Vincent's Medical Center	Jacksonville	Florida	United States	32204
6	Northwestern University	Chicago	Illinois	United States	60611
7	NorthShore University Health System	Evanston	Illinois	United States	60201-1718
8	The Johns Hopkins Hospital	Baltimore	Maryland	United States	21287-0005
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	St. Luke's Health System	Kansas City	Missouri	United States	64111
11	Englewood Hospital & Medical Center	Englewood	New Jersey	United States	07631-1808
12	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
13	Northwell Health (Lenox Hill Hospital and Staten Island University Hospital)	New York	New York	United States	10075-1851
14	Asheville Cardiology Associates	Asheville	North Carolina	United States	28803
15	Doylestown Health Cardiology	Doylestown	Pennsylvania	United States	18901
16	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-8802
17	Baylor Research Institute	Dallas	Texas	United States	75226
18	Virginia Mason Medical Center	Seattle	Washington	United States	98101
19	Swedish Medical Center	Seattle	Washington	United States	98122
20	Victoria Cardiac Arrhythmia Trials	Victoria	British Columbia	Canada	V8T 1Z4
21	London Health Sciences Centre	London	Ontario	Canada	N6A 5A5
22	Institut Universitaire de Cardiologie et de Pneumologie de Québec	Quebec		Canada	G1V 4G5
23	Tokyo Medical and Dental University	Bunkyō	Tokyo	Japan	113-8519
24	Jikei University Hospital	Tokyo		Japan
25	Yokohama City Minato Red Cross Hospital	Yokohama		Japan	231-8682

Sponsors and Collaborators

• Medtronic Cardiac Rhythm and Heart Failure

Investigators

• Principal Investigator: Hugh Calkins, MD, Johns Hopkins University
• Principal Investigator: Vivek Reddy, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

• Statistical Analysis Plan - Jul 8, 2019
• Study Protocol: Version 4 - Nov 10, 2016
• Study Protocol: Version 5 - Apr 17, 2017
• Study Protocol: Version 6 - Dec 1, 2017

More Information

Publications

None provided.

• Responsible Party: Medtronic Cardiac Rhythm and Heart Failure
• ClinicalTrials.gov Identifier: NCT03012841
• Other Study ID Numbers: STOP Persistent AF
• First Posted: Jan 6, 2017
• Last Update Posted: Oct 8, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Atrial Fibrillation

Study Results

Participant Flow

Arm/Group Title	Modified Intent to Treat (mITT) Group	Not Treated
Arm/Group Description	Subjects enrolled and treated with Arctic Front Advance Cardiac CryoAblation Catheter	Subjects enrolled, but not treated with an Arctic Front Advance Cryoablation catheter.
Period Title: Overall Study
STARTED	165	21
COMPLETED	145	0
NOT COMPLETED	20	21

Baseline Characteristics

Arm/Group Title	Modified Intent to Treat Group (mITT)
Arm/Group Description	Subjects enrolled and treated with Arctic Front Advance Cardiac CryoAblation Catheter
Overall Participants	165
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (9)
Sex: Female, Male (Count of Participants)
Female	49 29.7%
Male	116 70.3%
Race/Ethnicity, Customized (Count of Participants)
White or Caucasian	142 86.1%
Japanese	15 9.1%
Black	2 1.2%
Filipino	1 0.6%
Other Asian	1 0.6%
Subject/physician chose not to provide	4 2.4%
Region of Enrollment (participants) [Number]
Canada	30 18.2%
United States	120 72.7%
Japan	15 9.1%
Time from Persistent Atrial Fibrillation (AF) Onset (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	0.6 (1.4)
Duration of Longest Persistent AF Episode (days) [Median (Full Range) ]
Median (Full Range) [days]	60.9

Outcome Measures

1. Primary Outcome

Title	Percent of Subjects Free From Treatment Failure at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure.
Description	Treatment failure is defined as any of the following components: Acute procedural failure Documented AF/atrial tachycardia (AT)/atrial flutter (AFL) after the 90 day blanking period A reablation for the treatment of recurrent AF/AT/AFL after the 90 day blanking period Class I or III antiarrhythmic drug (AAD) dose increase from the historic maximum ineffective dose (prior to the ablation procedure) or initiation of a new Class I or III AAD after the 90 day blanking period. Ablation using radiofrequency (RF) in the left atrium Blanking period is defined as the first 90 days after the index ablation procedure. Acute procedural failure is defined as: Inability to isolate all accessible targeted pulmonary veins (minimally assessed for entrance block and, where assessable, exit block) during the index procedure Left atrial non-PVI ablations including but not limited to, ablation of linear lesions complex fractionated electrograms or non-PV triggers
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modified Intent to Treat Group (mITT)
Arm/Group Description	Subjects enrolled and treated with Arctic Front Advance Cardiac CryoAblation Catheter
Measure Participants	165
Number (95% Confidence Interval) [percentage of participants]	54.8 33.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modified Intent to Treat Group (mITT)
	Comments
	Type of Statistical Test	Superiority
	Comments	The formal alternative hypothesis test for the primary effectiveness objective was that the Kaplan-Meier estimator of treatment success at 12 months (365 days) was greater than 40%, against the null hypothesis that it was less than or equal to 40%.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Exact binomial
	Comments	Exact binomial p-value is shown, but the confidence intervals reported are calculated from Greenwood's approximation of the standard error.
Method of Estimation	Estimation Parameter	Kaplan-Meier (product-limit) estimator
	Estimated Value	54.8
	Confidence Interval	(2-Sided) 95%; 46.7 to 62.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percent of Subjects Free From a Primary Safety Event at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure.
Description	A primary safety event is defined as a serious procedure-related or serious system-related adverse event including the following: Transient ischemic attack (within 7 days of ablation procedure) Cerebrovascular accident (within 7 days of ablation procedure) Major bleeding that requires transfusion (within 7 days of ablation procedure) Cardiac perforation, tamponade or pericardial effusion (within 7 days of ablation procedure) Pulmonary vein stenosis (> 75% reduction within 12-months of ablation procedure) Myocardial infarction (within 7 days of ablation procedure) Phrenic nerve injury (unresolved at 12-months) Atrio-esophageal fistula (within 12-months of ablation procedure) Death (within 7 days of ablation procedure)
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modified Intent to Treat Group (mITT)
Arm/Group Description	Subjects enrolled and treated with Arctic Front Advance Cardiac CryoAblation Catheter
Measure Participants	165
Number (95% Confidence Interval) [percentage of participants]	0.6 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modified Intent to Treat Group (mITT)
	Comments
	Type of Statistical Test	Superiority
	Comments	The formal alternative hypothesis tested for the primary safety objective was that the Kaplan-Meier estimator of the proportion of subjects with primary safety events at 12 months (365 days) was less than 13%, against the null hypothesis that it was greater than or equal to 13%.
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Exact binomial
	Comments	Exact binomial p-value is shown, but the confidence intervals reported are calculated from Greenwood's approximation of the standard error.
Method of Estimation	Estimation Parameter	Kaplan-Meier (product-limit) estimator
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; 0.1 to 4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in Quality of Life Between Baseline and 12 Months: Atrial Fibrillation Effect on QualiTy-of-life (AFEQT)
Description	Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire completed at baseline and 12 month visits. The AFEQT instrument yields scores from 0 (representing the worst possible debilitation from AF) to 100 (representing no reduction in quality of life from AF).
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Treated subjects completing at least 50% of questions on AFEQT questionnaires at both baseline and 12-month visits

Arm/Group Title	Treated 12-month Completers
Arm/Group Description	Subjects enrolled and treated with Arctic Front Advance Cardiac CryoAblation Catheter who had complete QoL questionnaires at baseline and follow-up
Measure Participants	141
Mean (95% Confidence Interval) [score on a scale]	25.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modified Intent to Treat Group (mITT)
	Comments	The formal alternative hypothesis tested was that the mean 12-month change in AFEQT composite scores was greater than 0, against the null the hypothesis that it was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	A Hommel multiple testing procedure was utilized to maintain overall alpha of 0.025 for the 3 hypotheses tested for the secondary objective.
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	25.8
	Confidence Interval	(2-Sided) 95%; 22.1 to 29.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Physical Component
Description	Medical Outcome Study Short Form-12 (SF-12) questionnaire completed at baseline and 12 month visits. The SF-12 instrument has two composite scores, one for physical health and one for mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life).
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Treated subjects fully completing SF-12 questionnaires at both baseline and 12-month visits

Arm/Group Title	Treated 12-month Completers
Arm/Group Description	Subjects enrolled and treated with Arctic Front Advance Cardiac CryoAblation Catheter who had complete QoL questionnaires at baseline and follow-up
Measure Participants	142
Mean (95% Confidence Interval) [score on a scale]	5.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modified Intent to Treat Group (mITT)
	Comments	The formal alternative hypothesis tested was that the mean 12-month change in SF-12 physical composite scores was greater than 0, against the null the hypothesis that it was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	A Hommel multiple testing procedure was utilized to maintain overall alpha of 0.025 for the 3 hypotheses tested for the secondary objective.
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.0
	Confidence Interval	(2-Sided) 95%; 3.5 to 6.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Mental Component
Description	Medical Outcome Study Short Form-12 (SF-12) questionnaire completed at baseline and 12 month visits. The SF-12 instrument has two composite scores, one for physical health and one for mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life).
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Treated subjects fully completing SF-12 questionnaires at both baseline and 12-month visits

Arm/Group Title	Treated 12-month Completers
Arm/Group Description	Subjects enrolled and treated with Arctic Front Advance Cardiac CryoAblation Catheter who had complete QoL questionnaires at baseline and follow-up
Measure Participants	142
Mean (95% Confidence Interval) [score on a scale]	4.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modified Intent to Treat Group (mITT)
	Comments	The formal alternative hypothesis tested was that the mean 12-month change in SF-12 mental composite scores was greater than 0, against the null the hypothesis that it was equal to 0.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	A Hommel multiple testing procedure was utilized to maintain overall alpha of 0.025 for the 3 hypotheses tested for the secondary objective.
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.9
	Confidence Interval	(2-Sided) 95%; 3.2 to 6.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	All adverse events were collected between subject consent (enrollment) and study completion (1 year post study cryoablation procedure)
Arm/Group Title	Enrolled Subjects
Arm/Group Description	All enrolled and consented subjects
All Cause Mortality
	Enrolled Subjects
	Affected / at Risk (%)	# Events
Total	0/186 (0%)
Serious Adverse Events
	Enrolled Subjects
	Affected / at Risk (%)	# Events
Total	34/186 (18.3%)
Blood and lymphatic system disorders
Anaemia	2/186 (1.1%)	2
Cardiac disorders
Atrial fibrillation	10/186 (5.4%)	11
Acute myocardial infarction	1/186 (0.5%)	1
Angina pectoris	1/186 (0.5%)	1
Atrial tachycardia	1/186 (0.5%)	1
Cardiac failure	1/186 (0.5%)	1
Cardiac failure acute	1/186 (0.5%)	1
Cardiac failure congestive	1/186 (0.5%)	1
Pericarditis	1/186 (0.5%)	1
Gastrointestinal disorders
Crohn's disease	1/186 (0.5%)	1
Odynophagia	1/186 (0.5%)	1
Vomiting	1/186 (0.5%)	1
General disorders
Puncture site haematoma	1/186 (0.5%)	1
Hepatobiliary disorders
Cholecystitis chronic	1/186 (0.5%)	1
Infections and infestations
Bacterial sepsis	1/186 (0.5%)	1
Bronchitis	1/186 (0.5%)	1
Diverticulitis	1/186 (0.5%)	1
Herpes zoster	1/186 (0.5%)	1
Labyrinthitis	1/186 (0.5%)	1
Pneumonia	1/186 (0.5%)	1
Urinary tract infection	1/186 (0.5%)	1
Injury, poisoning and procedural complications
Vascular pseudoaneurysm	2/186 (1.1%)	2
Postoperative ileus	1/186 (0.5%)	1
Ureteric injury	1/186 (0.5%)	1
Metabolism and nutrition disorders
Fluid retention	1/186 (0.5%)	1
Hyponatremia	1/186 (0.5%)	1
Musculoskeletal and connective tissue disorders
Neck mass	1/186 (0.5%)	1
Osteoarthritis	1/186 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/186 (0.5%)	1
Lung neoplasm malignant	1/186 (0.5%)	1
Squamous cell carcinoma of the tongue	1/186 (0.5%)	1
Nervous system disorders
Hemiparesis	1/186 (0.5%)	1
Renal and urinary disorders
Acute kidney injury	1/186 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/186 (0.5%)	1
Pneumothorax	1/186 (0.5%)	1
Respiratory failure	1/186 (0.5%)	1
Vascular disorders
Aortic perforation	1/186 (0.5%)	1
Hypertension	1/186 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Enrolled Subjects
	Affected / at Risk (%)	# Events
Total	52/186 (28%)
Cardiac disorders
Atrial fibrillation	44/186 (23.7%)	62
Atrial flutter	20/186 (10.8%)	24

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Principle Investigator (PI) agrees they will not independently discuss or publish trial results until a multi-center publication is released. If a multi-center publication is not released within one year after completion of the Study at all Study sites, PIs will have the right to publish the results of and information pertaining to their activities. Any such Publication must be submitted to Medtronic for review and comment at least sixty (60) days prior to submission or presentation.