Trial Outcomes & Findings for FIRE AND ICE: Comparative Study of Two Ablation Procedures in Patients With Atrial Fibrillation (NCT NCT01490814)

NCT ID: NCT01490814

Last Updated: 2018-11-02

Results Overview

Number of subjects reporting a primary efficacy endpoint

Recruitment status

COMPLETED

Study phase

Target enrollment

769 participants

Primary outcome timeframe

33 months

Results posted on

2018-11-02

Participant Flow

769 subjects were enrolled; 7 subjects exited prior to randomization, 762 were randomized

Participant milestones

Participant milestones
Measure	Cryoballoon Ablation Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Overall Study STARTED	378	384
Overall Study COMPLETED	374	376
Overall Study NOT COMPLETED	4	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Cryoballoon Ablation Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Overall Study Inclusion/Exclusion Criteria Violation	3	3
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	0	5

Baseline Characteristics

FIRE AND ICE: Comparative Study of Two Ablation Procedures in Patients With Atrial Fibrillation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cryoballoon Ablation n=374 Participants Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 Participants Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Total n=750 Participants Total of all reporting groups
Age, Continuous	59.9 years STANDARD_DEVIATION 9.8 • n=93 Participants	60.1 years STANDARD_DEVIATION 9.2 • n=4 Participants	60.0 years STANDARD_DEVIATION 9.5 • n=27 Participants
Sex: Female, Male Female	153 Participants n=93 Participants	140 Participants n=4 Participants	293 Participants n=27 Participants
Sex: Female, Male Male	221 Participants n=93 Participants	236 Participants n=4 Participants	457 Participants n=27 Participants
Years since first PAF diagnosis	4.6 years STANDARD_DEVIATION 5.1 • n=93 Participants	4.7 years STANDARD_DEVIATION 5.3 • n=4 Participants	4.6 years STANDARD_DEVIATION 5.2 • n=27 Participants

PRIMARY outcome

Timeframe: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

Number of subjects reporting a primary efficacy endpoint

Outcome measures

Outcome measures
Measure	Cryoballoon Ablation n=374 Participants Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 Participants Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Number of Subjects With Recurrence of Atrial Arrhythmias or Prescription of Anti-arrhythmic Drug or Re-ablation After a Blanking Period of Three Months After the Initial Ablation Procedure	138 Participants	143 Participants

PRIMARY outcome

Timeframe: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

Outcome measures

Outcome measures
Measure	Cryoballoon Ablation n=374 Participants Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 Participants Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Number of Subjects With a Primary Safety Event. A Primary Safety Event Includes a Composite of Death (Including Cardiovascular Death), All-cause Stroke/Transient Ischemic Attack (TIA) and Serious Adverse Events of Special Interest. No primary safety event	334 Participants	325 Participants
Number of Subjects With a Primary Safety Event. A Primary Safety Event Includes a Composite of Death (Including Cardiovascular Death), All-cause Stroke/Transient Ischemic Attack (TIA) and Serious Adverse Events of Special Interest. Death	2 Participants	0 Participants
Number of Subjects With a Primary Safety Event. A Primary Safety Event Includes a Composite of Death (Including Cardiovascular Death), All-cause Stroke/Transient Ischemic Attack (TIA) and Serious Adverse Events of Special Interest. All-cause stroke or TIA	2 Participants	2 Participants
Number of Subjects With a Primary Safety Event. A Primary Safety Event Includes a Composite of Death (Including Cardiovascular Death), All-cause Stroke/Transient Ischemic Attack (TIA) and Serious Adverse Events of Special Interest. Atrial Arrhythmia	8 Participants	13 Participants
Number of Subjects With a Primary Safety Event. A Primary Safety Event Includes a Composite of Death (Including Cardiovascular Death), All-cause Stroke/Transient Ischemic Attack (TIA) and Serious Adverse Events of Special Interest. Non-arrhythmia-related Serious Adverse Event	28 Participants	36 Participants

SECONDARY outcome

Timeframe: 33 months

Population: Subjects randomized and received ablation. Modified intent-to-treat (mITT) population.

Outcome measures

Outcome measures
Measure	Cryoballoon Ablation n=374 Participants Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 Participants Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
All-cause Death	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

Outcome measures

Outcome measures
Measure	Cryoballoon Ablation n=374 Participants Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 Participants Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Arrhythmia-related Death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Through the initial ablation procedure

Population: Subjects randomized and received ablation. Modified intent-to-treat (mITT) population.

Outcome measures

Outcome measures
Measure	Cryoballoon Ablation n=374 Participants Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 Participants Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Total Procedure Duration	124.4 minutes Standard Deviation 39.0	140.9 minutes Standard Deviation 54.9

SECONDARY outcome

Timeframe: Fluoroscopy meter time through the initial ablation procedure

Population: Subjects randomized and received ablation procedure. Modified intent-to-treat (mITT) population

Outcome measures

Outcome measures
Measure	Cryoballoon Ablation n=374 Participants Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 Participants Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Total Time of Fluoroscopy	16.6 minutes Standard Deviation 17.8	21.7 minutes Standard Deviation 13.9

SECONDARY outcome

Timeframe: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

Outcome measures

Outcome measures
Measure	Cryoballoon Ablation n=374 Participants Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 Participants Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Number of Subjects Reporting a Cardiovascular Hospitalization Over the Duration of the Study.	89 Participants	135 Participants

SECONDARY outcome

Timeframe: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

The total number of cardiovascular hospitalizations reported over the duration of the study.

Outcome measures

Outcome measures
Measure	Cryoballoon Ablation n=374 Participants Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 Participants Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Number of Cardiovascular Hospitalizations	139 number of cardiovascular hospitalization	203 number of cardiovascular hospitalization

Adverse Events

Cryoballoon Ablation

Serious events: 129 serious events

Other events: 0 other events

Deaths: 0 deaths

Radiofrequency Ablation

Serious events: 158 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Ralf Meyer

Medtronic

Phone: +49215981490

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Cryoballoon Ablation n=374 participants at risk Electrical isolation of the pulmonary veins: Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.	Radiofrequency Ablation n=376 participants at risk Electrical isolation of pulmonary veins: Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	0.53% 2/374 • Number of events 2 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Injury, poisoning and procedural complications ACCIDENT	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
General disorders ADVERSE DRUG REACTION	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Injury, poisoning and procedural complications ANESTHETIC COMPLICATION PULMONARY	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Cardiac disorders ANGINA PECTORIS	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Cardiac disorders ANGINA UNSTABLE	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Psychiatric disorders ANXIETY	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Vascular disorders AORTIC ANEURYSM	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Vascular disorders AORTIC DISSECTION	0.27% 1/374 • Number of events 2 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Investigations ARTERIOGRAM CORONARY	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Vascular disorders ARTERIOVENOUS FISTULA	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.80% 3/376 • Number of events 3 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Vascular disorders ARTERITIS	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Respiratory, thoracic and mediastinal disorders ASPIRATION	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
General disorders ASTHENIA	0.53% 2/374 • Number of events 2 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.53% 2/376 • Number of events 2 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Cardiac disorders ATRIAL FIBRILLATION	14.4% 54/374 • Number of events 69 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	22.9% 86/376 • Number of events 110 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Cardiac disorders ATRIAL FLUTTER	2.1% 8/374 • Number of events 10 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	3.2% 12/376 • Number of events 13 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Congenital, familial and genetic disorders ATRIAL SEPTAL DEFECT	0.27% 1/374 • Number of events 2 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Cardiac disorders ATRIAL TACHYCARDIA	1.3% 5/374 • Number of events 6 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	1.9% 7/376 • Number of events 7 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Cardiac disorders ATRIOVENTRICULAR BLOCK SECOND DEGREE	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Reproductive system and breast disorders BENIGN PROSTATIC HYPERPLASIA	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.53% 2/376 • Number of events 2 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BENIGN SALIVARY GLAND NEOPLASM	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Hepatobiliary disorders BILIARY COLIC	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Surgical and medical procedures BRACHYTHERAPY TO UTERUS	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Cardiac disorders BRADYCARDIA	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BRONCHIAL NEOPLASM BENIGN	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Infections and infestations BRONCHITIS	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Musculoskeletal and connective tissue disorders BURSITIS	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CARCINOID TUMOUR OF THE CAECUM	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Surgical and medical procedures CARDIAC ABLATION	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Cardiac disorders CARDIAC FAILURE	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Cardiac disorders CARDIAC TAMPONADE	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	1.1% 4/376 • Number of events 4 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Nervous system disorders CEREBELLAR INFARCTION	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Nervous system disorders CEREBRAL HEMORRHAGE	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Injury, poisoning and procedural complications CERVICAL VERTEBRAL FRACTURE	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
General disorders CHEST PAIN	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Respiratory, thoracic and mediastinal disorders CHOKING	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.00% 0/376 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Surgical and medical procedures CHOLECYSTECTOMY	0.00% 0/374 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.
Hepatobiliary disorders CHOLECYSTITIS	0.27% 1/374 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.	0.27% 1/376 • Number of events 1 • The duration of the study. Mean follow-up was 1.5 years, maximum follow-up was 33 months.