Cryoablation System FIM/CE Mark Study

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03723070
• Collaborator: Cryterion Medical, Inc. (Industry)
• Enrollment: 88
• Locations: 4
• Arm: 1
• Actual Duration (Months): 31.3
• Patients Per Site: 22
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Multi-center, open label, prospective clinical study to establish the acute safety and performance of the Cryterion Cardiac Cryoablation System

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Device: The Cryterion Cardiac Cryoablation System	N/A

Detailed Description

This is a single-arm, open-label clinical study using a cryoablation balloon device to isolate pulmonary veins during an atrial fibrillation ablation procedure. Cryo is a scientifically proven energy source used to create a thermal injury during endocardial ablation. The investigational device uses current technology with minor design modifications and will be studied to validate similarities in the safety and performance parameters compared to literature.

Study Design

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Non-randomized study designed to validate the safety and performance of the Cryterion Cardiac Cryoablation System when used as intendedNon-randomized study designed to validate the safety and performance of the Cryterion Cardiac Cryoablation System when used as intended
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cryterion Cardiac Cryoablation System CE Mark Study
• Actual Study Start Date: May 15, 2018
• Actual Primary Completion Date: Dec 22, 2020
• Actual Study Completion Date: Dec 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PV Cryoablation Ablation of the ostium of the pulmonary veins (PV) as a means to electrically isolate the veins in the treatment of atrial fibrillation. A cryoablation balloon will be inserted into the left atrium and cryo applications will be administered to create an endocardial thermal injury by using the Cryterion Cardiac Cryoablation System	Device: The Cryterion Cardiac Cryoablation System; Cryoablation System that includes a Balloon Catheter, Circular Mapping Catheter, Steerable Sheath and Cryoablation Console. In combination, components of the System will be inserted into the left atrium and a thermal injury at the PV ostium will be created to electrically isolate the veins

Outcome Measures

Primary Outcome Measures

1. Primary Safety Outcome: Percentage of Participants With Procedure Related Adverse Events OR Device Related Adverse Events OR Serious Adverse Device Effects [12 months]

   Percentage of participants with procedure related adverse events OR device related adverse events OR Serious Adverse device effects including: Death, Myocardial Infarction, Cardiac perforation/pericardial tamponade, Cerebral Infarct or systemic embolism, Major bleeding requiring transfusion of blood products, Mitral or tricuspid valvular damage, phrenic nerve damage causing persistent diaphragmatic paralysis, Symptomatic pulmonary vein stenosis, atrio-esophageal fistula, Air embolism leading to life-threatening event, other serious adverse device effects (SADEs)

2. Acute Procedural Success [Following the last cryo-application for each of the targeted veins, during the index procedure. Mean procedure time was 118 minutes.]

   Percentage of patients achieving pulmonary vein isolation defined as entrance and exit block for each of the targeted pulmonary veins following the last ablation application.

3. 12 Month Treatment Success - Percentage of Subjects Free From Arrhythmias at 12 Months [12 months]

   A treatment failure is defined as a subject being an acute procedural failure, having more than one repeat procedure during the 90-day blanking period or having a documented, symptomatic episode(s) of atrial fibrillation or atrial tachycardia, between 91 and 365 days post index procedure. Occurrence or recurrence of a right atrial arrhythmia is not considered a treatment failure post the 90-day blanking period

Secondary Outcome Measures

1. Secondary Safety Outcome: Number of Procedure-related or Device Related Adverse Events. [12 months]

   All procedure-related or device related adverse events with causal relationship

2. Percentage of Subjects With Isolation Immediately Post Ablation and With Reconnection During the Entrance/Exit Block Testing [30 minutes]

   Percentage of subjects that present PV isolation immediately after ablation but show reconnection after 30 minutes during entrance/exit block testing. This outcome is only measured in subjects that were enrolled under the protocol that required a 30 minute waiting period between isolation and verification of isolation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Inclusion Criteria:

• Currently scheduled for a de novo ablation of atrial fibrillation (AF) defined as AF with self-terminating episodes lasting no longer than 7 continuous days (PAF)

Main Exclusion Criteria:

• In the opinion of the Investigator, any known contraindication to an AF ablation, Transesophageal Echocardiogram (TEE). or anticoagulation

• Any duration of continuous AF lasting longer than 7 days

• History of previous left atrial ablation or surgical treatment for Atrial Fibrillation/Atrial Flutter/Atrial Tachycardia (AF/AFL/AT)

• More than four (4) electrical cardioversions in the year prior to enrollment excluding cardioversions performed within 24 hours of arrhythmia onset.

• Significant structural heart disease or implanted cardiac devices

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Hospital Centre Split	Split		Croatia
2	Catharina Ziekenhuis	Eindhoven		Netherlands
3	Erasmus MC	Rotterdam		Netherlands
4	Auckland City Hospital	Auckland		New Zealand

Sponsors and Collaborators

• Boston Scientific Corporation
• Cryterion Medical, Inc.

Investigators

• Study Director: Sarfaraz Taher, Boston Scientific Corporation

Study Documents (Full-Text)

• Study Protocol - Sep 4, 2019
• Statistical Analysis Plan - Mar 1, 2021

More Information

Publications

None provided.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT03723070
• Other Study ID Numbers: CEM-A02-02
• First Posted: Oct 29, 2018
• Last Update Posted: Jul 19, 2021
• Last Verified: Jun 1, 2021

• 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: No
• Additional relevant MeSH terms: Atrial Fibrillation

Study Results

Participant Flow

Arm/Group Title	PV Cryoablation
Arm/Group Description	Ablation of the ostium of the pulmonary veins (PV) as a means to electrically isolate the veins in the treatment of atrial fibrillation. A cryoablation balloon will be inserted into the left atrium and cryo applications will be administered to create an endocardial thermal injury by using the Cryterion Cardiac Cryoablation System The Cryterion Cardiac Cryoablation System: Cryoablation System that includes a Balloon Catheter, Circular Mapping Catheter, Steerable Sheath and Cryoablation Console. In combination, components of the System will be inserted into the left atrium and a thermal injury at the PV ostium will be created to electrically isolate the veins
Period Title: Overall Study
STARTED	88
COMPLETED	79
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	PV Cryoablation
Arm/Group Description	Ablation of the ostium of the pulmonary veins (PV) as a means to electrically isolate the veins in the treatment of atrial fibrillation. A cryoablation balloon will be inserted into the left atrium and cryo applications will be administered to create an endocardial thermal injury by using the Cryterion Cardiac Cryoablation System The Cryterion Cardiac Cryoablation System: Cryoablation System that includes a Balloon Catheter, Circular Mapping Catheter, Steerable Sheath and Cryoablation Console. In combination, components of the System will be inserted into the left atrium and a thermal injury at the PV ostium will be created to electrically isolate the veins
Overall Participants	88
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (11)
Sex: Female, Male (Count of Participants)
Female	34 38.6%
Male	54 61.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	81 92%
More than one race	0 0%
Unknown or Not Reported	6 6.8%
Region of Enrollment (participants) [Number]
New Zealand	15 17%
Netherlands	9 10.2%
Croatia	64 72.7%

Outcome Measures

1. Primary Outcome

Title	Primary Safety Outcome: Percentage of Participants With Procedure Related Adverse Events OR Device Related Adverse Events OR Serious Adverse Device Effects
Description	Percentage of participants with procedure related adverse events OR device related adverse events OR Serious Adverse device effects including: Death, Myocardial Infarction, Cardiac perforation/pericardial tamponade, Cerebral Infarct or systemic embolism, Major bleeding requiring transfusion of blood products, Mitral or tricuspid valvular damage, phrenic nerve damage causing persistent diaphragmatic paralysis, Symptomatic pulmonary vein stenosis, atrio-esophageal fistula, Air embolism leading to life-threatening event, other serious adverse device effects (SADEs)
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PV Cryoablation
Arm/Group Description	Ablation of the ostium of the pulmonary veins (PV) as a means to electrically isolate the veins in the treatment of atrial fibrillation. A cryoablation balloon will be inserted into the left atrium and cryo applications will be administered to create an endocardial thermal injury by using the Cryterion Cardiac Cryoablation System The Cryterion Cardiac Cryoablation System: Cryoablation System that includes a Balloon Catheter, Circular Mapping Catheter, Steerable Sheath and Cryoablation Console. In combination, components of the System will be inserted into the left atrium and a thermal injury at the PV ostium will be created to electrically isolate the veins
Measure Participants	88
Count of Participants [Participants]	50 56.8%

2. Primary Outcome

Title	Acute Procedural Success
Description	Percentage of patients achieving pulmonary vein isolation defined as entrance and exit block for each of the targeted pulmonary veins following the last ablation application.
Time Frame	Following the last cryo-application for each of the targeted veins, during the index procedure. Mean procedure time was 118 minutes.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PV Cryoablation
Arm/Group Description	Ablation of the ostium of the pulmonary veins (PV) as a means to electrically isolate the veins in the treatment of atrial fibrillation. A cryoablation balloon will be inserted into the left atrium and cryo applications will be administered to create an endocardial thermal injury by using the Cryterion Cardiac Cryoablation System The Cryterion Cardiac Cryoablation System: Cryoablation System that includes a Balloon Catheter, Circular Mapping Catheter, Steerable Sheath and Cryoablation Console. In combination, components of the System will be inserted into the left atrium and a thermal injury at the PV ostium will be created to electrically isolate the veins
Measure Participants	88
Count of Participants [Participants]	87 98.9%

3. Primary Outcome

Title	12 Month Treatment Success - Percentage of Subjects Free From Arrhythmias at 12 Months
Description	A treatment failure is defined as a subject being an acute procedural failure, having more than one repeat procedure during the 90-day blanking period or having a documented, symptomatic episode(s) of atrial fibrillation or atrial tachycardia, between 91 and 365 days post index procedure. Occurrence or recurrence of a right atrial arrhythmia is not considered a treatment failure post the 90-day blanking period
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

In total, 88 subjects were enrolled. Six subjects ended the study at the one month follow-up visit and were therefore not eligible for the analysis. Of the 3 subjects that were withdrawn prior to study completion, one subject experienced a recurrence before being withdrawn and was therefore included in the analysis. The two other subjects were event free at time of study withdrawal.

Arm/Group Title	PV Cryoablation
Arm/Group Description	Ablation of the ostium of the pulmonary veins (PV) as a means to electrically isolate the veins in the treatment of atrial fibrillation. A cryoablation balloon will be inserted into the left atrium and cryo applications will be administered to create an endocardial thermal injury by using the Cryterion Cardiac Cryoablation System The Cryterion Cardiac Cryoablation System: Cryoablation System that includes a Balloon Catheter, Circular Mapping Catheter, Steerable Sheath and Cryoablation Console. In combination, components of the System will be inserted into the left atrium and a thermal injury at the PV ostium will be created to electrically isolate the veins
Measure Participants	80
Count of Participants [Participants]	58 65.9%

4. Secondary Outcome

Title	Secondary Safety Outcome: Number of Procedure-related or Device Related Adverse Events.
Description	All procedure-related or device related adverse events with causal relationship
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Causally related to procedure

Arm/Group Title	PV Cryoablation
Arm/Group Description	Ablation of the ostium of the pulmonary veins (PV) as a means to electrically isolate the veins in the treatment of atrial fibrillation. A cryoablation balloon will be inserted into the left atrium and cryo applications will be administered to create an endocardial thermal injury by using the Cryterion Cardiac Cryoablation System The Cryterion Cardiac Cryoablation System: Cryoablation System that includes a Balloon Catheter, Circular Mapping Catheter, Steerable Sheath and Cryoablation Console. In combination, components of the System will be inserted into the left atrium and a thermal injury at the PV ostium will be created to electrically isolate the veins
Measure Participants	88
Number [Adverse Events]	12

5. Secondary Outcome

Title	Percentage of Subjects With Isolation Immediately Post Ablation and With Reconnection During the Entrance/Exit Block Testing
Description	Percentage of subjects that present PV isolation immediately after ablation but show reconnection after 30 minutes during entrance/exit block testing. This outcome is only measured in subjects that were enrolled under the protocol that required a 30 minute waiting period between isolation and verification of isolation.
Time Frame	30 minutes

Outcome Measure Data

Analysis Population Description

Out of 88 subjects enrolled in the study, 54 subjects have been enrolled under the protocol requiring a 30 minute waiting period between pulmonary vein isolation and entrance/exit block testing. All subjects for whom at least one additional application was performed minimally 30 minutes after the previous ablation, were considered having a potential reconnection during entrance/exit block testing.

Arm/Group Title	PV Cryoablation
Arm/Group Description	Ablation of the ostium of the pulmonary veins (PV) as a means to electrically isolate the veins in the treatment of atrial fibrillation. A cryoablation balloon will be inserted into the left atrium and cryo applications will be administered to create an endocardial thermal injury by using the Cryterion Cardiac Cryoablation System The Cryterion Cardiac Cryoablation System: Cryoablation System that includes a Balloon Catheter, Circular Mapping Catheter, Steerable Sheath and Cryoablation Console. In combination, components of the System will be inserted into the left atrium and a thermal injury at the PV ostium will be created to electrically isolate the veins
Measure Participants	54
Count of Participants [Participants]	7 8%

Adverse Events

Time Frame	12 months
Arm/Group Title	PV Cryoablation
Arm/Group Description	Ablation of the ostium of the pulmonary veins (PV) as a means to electrically isolate the veins in the treatment of atrial fibrillation. A cryoablation balloon will be inserted into the left atrium and cryo applications will be administered to create an endocardial thermal injury by using the Cryterion Cardiac Cryoablation System The Cryterion Cardiac Cryoablation System: Cryoablation System that includes a Balloon Catheter, Circular Mapping Catheter, Steerable Sheath and Cryoablation Console. In combination, components of the System will be inserted into the left atrium and a thermal injury at the PV ostium will be created to electrically isolate the veins
All Cause Mortality
	PV Cryoablation
	Affected / at Risk (%)	# Events
Total	0/88 (0%)
Serious Adverse Events
	PV Cryoablation
	Affected / at Risk (%)	# Events
Total	6/88 (6.8%)
Cardiac disorders
Atrial Arrhythmia	1/88 (1.1%)	1
Gastrointestinal disorders
Hematochezia	1/88 (1.1%)	1
Cholecystitis	1/88 (1.1%)	1
Cholelithiasis	1/88 (1.1%)	1
Nervous system disorders
Episodic aphasia	1/88 (1.1%)	1
Vascular disorders
Embolism in right femoral artery	1/88 (1.1%)	1
Other (Not Including Serious) Adverse Events
	PV Cryoablation
	Affected / at Risk (%)	# Events
Total	56/88 (63.6%)
Blood and lymphatic system disorders
Hypersaturation with warfarin	1/88 (1.1%)	1
Cardiac disorders
Angina/Chest pain	4/88 (4.5%)	5
Pericardial effusion	1/88 (1.1%)	1
Adverse reaction - hypotension	3/88 (3.4%)	3
Palpitations	27/88 (30.7%)	38
Atrial Arrhythmia	10/88 (11.4%)	11
Syncope	1/88 (1.1%)	1
Diziness	2/88 (2.3%)	2
Chest Pain	3/88 (3.4%)	3
Dyspnea	1/88 (1.1%)	1
Fatigue/Weakness	3/88 (3.4%)	3
Inability to palpate peripheral arterial pulse	1/88 (1.1%)	1
CVA	1/88 (1.1%)	1
Endocrine disorders
Elevated level Thyroid function (T4)	1/88 (1.1%)	1
Type 2 Diabetes Mellitus	1/88 (1.1%)	1
Eye disorders
Cataract	1/88 (1.1%)	1
Conjunctavitis	1/88 (1.1%)	1
Gastrointestinal disorders
Adverse reaction Anesthesia/sedation	2/88 (2.3%)	2
Adverse reaction - gastrointestinal	3/88 (3.4%)	3
Gastritis	1/88 (1.1%)	1
Dysphagia	1/88 (1.1%)	1
Odynophagia	1/88 (1.1%)	1
Polipectomy	1/88 (1.1%)	1
Heartburn	1/88 (1.1%)	1
Constipation	1/88 (1.1%)	1
Diarrhoea	1/88 (1.1%)	1
Polyp in acsending colon	1/88 (1.1%)	1
Tooth Pain	1/88 (1.1%)	1
General disorders
Adverse reactions	1/88 (1.1%)	1
Adverse Reaction - Urticaria	1/88 (1.1%)	1
Adverse Reaction - Medication	1/88 (1.1%)	1
Hipoechogenic lesion in left breast	1/88 (1.1%)	1
Infections and infestations
Fever - Virus	3/88 (3.4%)	3
Infection	1/88 (1.1%)	2
Pharyngitis	1/88 (1.1%)	1
sinusitis	1/88 (1.1%)	1
Injury, poisoning and procedural complications
Sore Throat post procedure	1/88 (1.1%)	1
Musculoskeletal and connective tissue disorders
Back Pain	2/88 (2.3%)	2
Ankle Injury	1/88 (1.1%)	1
Muskuloskeletal	3/88 (3.4%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Follicular lymphoma	1/88 (1.1%)	1
Nervous system disorders
Nerve (weakness, palsy)	4/88 (4.5%)	4
Adverse reaction - neurological	1/88 (1.1%)	1
Shinlges	1/88 (1.1%)	1
Renal and urinary disorders
Urinary Infection	1/88 (1.1%)	1
Positive urine culture	1/88 (1.1%)	1
Benign renal cyst L) kidney	1/88 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Adverse reaction - pulmonary	1/88 (1.1%)	1
Skin and subcutaneous tissue disorders
Post surgical wound discomfort	2/88 (2.3%)	2
Hematoma	3/88 (3.4%)	3
Haematoma of the right upper arm	1/88 (1.1%)	1
Vascular disorders
Minor oozing/bleeding	3/88 (3.4%)	3
Epistaxis	1/88 (1.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.