Trial Outcomes & Findings for Hydrogel Endovascular Aneurysm Treatment Trial (NCT NCT01407952)

Last Updated: 2019-06-27

Results Overview

Defined as any progression on the Raymond-Roy (RR) Aneurysm Occlusion Scale. The RR scale is such that 1=complete occlusion, 2=residual neck, and 3=residual aneurysm.

Recruitment status

COMPLETED

Study phase

Target enrollment

600 participants

Primary outcome timeframe

post surgery to 24 months

Results posted on

2019-06-27

Participant Flow

Participant milestones

Participant milestones
Measure	HydroCoil Embolic System Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Overall Study STARTED	297	303
Overall Study COMPLETED	251	266
Overall Study NOT COMPLETED	46	37

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Hydrogel Endovascular Aneurysm Treatment Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HydroCoil Embolic System n=297 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=303 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils	Total n=600 Participants Total of all reporting groups
Age, Continuous	56.5 years STANDARD_DEVIATION 11.5 • n=5 Participants	56.9 years STANDARD_DEVIATION 10.3 • n=7 Participants	56.7 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	238 Participants n=5 Participants	236 Participants n=7 Participants	474 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	67 Participants n=7 Participants	126 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	243 Participants n=5 Participants	247 Participants n=7 Participants	490 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=5 Participants	48 Participants n=7 Participants	98 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	32 Participants n=5 Participants	27 Participants n=7 Participants	59 Participants n=5 Participants
Race (NIH/OMB) White	243 Participants n=5 Participants	247 Participants n=7 Participants	490 Participants n=5 Participants
Race (NIH/OMB) More than one race	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: post surgery to 24 months

Defined as any progression on the Raymond-Roy (RR) Aneurysm Occlusion Scale. The RR scale is such that 1=complete occlusion, 2=residual neck, and 3=residual aneurysm.

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=251 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=266 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Number of Patients With Aneurysm Recurrence Post Surgery	11 participants	41 participants

SECONDARY outcome

Timeframe: at operation

Population: Participants with both imaging data (to determine aneurysm size), and coil information (length, number, and type used)

Packing density as measured by volumetric filling of the aneurysm

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=238 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=237 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Packing Density	32.5 density as expressed as a percentage Standard Deviation 14.8	24.7 density as expressed as a percentage Standard Deviation 10.2

SECONDARY outcome

Timeframe: 24 months

Population: Based on participants with any post procedural follow-up.

modified rankin scale is a measure of neurological disability, which ranges from 0=no symptoms to 5=severe disability (6=dead).

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=287 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=292 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Clinical Outcome: Modified Rankin Scale (mRS) No symptoms (mRS=0)	181 Participants	178 Participants
Clinical Outcome: Modified Rankin Scale (mRS) No significant disability (mRS=1)	60 Participants	63 Participants
Clinical Outcome: Modified Rankin Scale (mRS) Slight disability (mRS=2)	24 Participants	28 Participants
Clinical Outcome: Modified Rankin Scale (mRS) Moderate disability (mRS=3)	13 Participants	10 Participants
Clinical Outcome: Modified Rankin Scale (mRS) Moderately severe disability (mRS=4)	2 Participants	0 Participants
Clinical Outcome: Modified Rankin Scale (mRS) Severe disability (mRS=5)	0 Participants	4 Participants
Clinical Outcome: Modified Rankin Scale (mRS) Expired (mRS=6)	7 Participants	9 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat population

number of participants who experienced any peri-procedural or post-procedural Adverse Event noted to be related to the procedure or device.

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=297 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=303 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Number of Participants With Adverse Events Related to the Procedure and/or the Device by Participant at Any Time in the Study.	64 Participants	75 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat population

total number of Adverse Events per person that were noted to be related to the procedure and device during the study

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=297 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=303 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. Three events	1 Participants	4 Participants
Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. No events	233 Participants	228 Participants
Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. One event	44 Participants	63 Participants
Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. Two events	19 Participants	8 Participants

SECONDARY outcome

Timeframe: 24 months

all-cause mortality at any time during study follow-up

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=297 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=303 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Number of Patients Who Expired During the Study (Mortality Rate)	7 Participants	9 Participants

SECONDARY outcome

Timeframe: at procedure

Population: Raymond-Roy Scale recorded at procedure

Raymond-Roy (RR) Scale=1 at procedure The RR scale is such that 1=complete occlusion, 2=residual neck, and 3=residual aneurysm.

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=281 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=290 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Number of Participants With Initial Complete Occlusion	50 Participants	82 Participants

SECONDARY outcome

Timeframe: 24 months

Population: participants with available followup

During the 24 month follow-up, if Aneurysm needed to be re-treated.

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=251 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=266 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Number of Patients Who Needed Re-treatment of Target Aneurysm	13 Participants	22 Participants

SECONDARY outcome

Timeframe: 24 months

Per the Adverse event log, if a hemorrhage or rupture occurred that was noted to be related to the procedure or device at any point during the 24 month follow-up (not during the operation).

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=297 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=303 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Number of Participants Experiencing a Hemorrhage From Target Aneurysm Post Surgery	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 24 months

Occlusion (in)stability was determined by progression on the Meyers scale. The Meyer scale is a 6-point grading scale based on the percentage of the aneurysm filled by contrast on DSA. Grade zero indicates complete and total aneurysm occlusion without remnant or in-terstitial filling within the aneurysm. Grade 1 represents greater than 90%volumetric occlusion of the aneurysm based on planar imaging assessment; grade 2, 70%-89% aneurysm occlusion; grade 3,50%-69%; grade 4, 25%-49%; and grade 5, less than 25% volumetric aneurysm occlusion.

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=251 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=266 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Number of Participants Who Progressed on the Meyers Scale	33 Participants	71 Participants

SECONDARY outcome

Timeframe: 24 months

Major recurrence is defined as progression on the Raymond-Roy (RR) Scale to 3, or if initial RR was 3, then progression on the Meyers scale. Minor recurrence was defined as a progression on the RR scale to 2. The RR scale is a 3 point measure of occlusion, 1=total, 2=residual neck, and 3=residual aneurysm. The Meyer scale is a 6-point grading scale based on the percentageof the aneurysm filled by contrast on DSA. Grade zero indicates complete and total aneurysm occlusion without remnant or in-terstitial filling within the aneurysm. Grade 1 represents \>90%volumetric occlusion of the aneurysm based on planar imaging assessment; grade 2, 70%-89% aneurysm occlusion; grade 3,50%-69%; grade 4, 25%-49%; and grade 5, \<25% volumetric aneurysm occlusion.

Outcome measures

Outcome measures
Measure	HydroCoil Embolic System n=251 Participants Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=266 Participants Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. Major recurrence	32 Participants	55 Participants
Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. Minor recurrence	2 Participants	14 Participants
Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. No major/minor recurrence	217 Participants	197 Participants

Adverse Events

HydroCoil Embolic System

Serious events: 61 serious events

Other events: 118 other events

Deaths: 7 deaths

Control

Serious events: 69 serious events

Other events: 140 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	HydroCoil Embolic System n=297 participants at risk Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=303 participants at risk Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Nervous system disorders Headache	12.8% 38/297 • Number of events 49 • Adverse event data was collected until 18-24 month visit.	16.5% 50/303 • Number of events 53 • Adverse event data was collected until 18-24 month visit.
Vascular disorders Vasospasm	5.1% 15/297 • Number of events 15 • Adverse event data was collected until 18-24 month visit.	5.9% 18/303 • Number of events 18 • Adverse event data was collected until 18-24 month visit.
Eye disorders Visual Disturbance	5.7% 17/297 • Number of events 17 • Adverse event data was collected until 18-24 month visit.	9.9% 30/303 • Number of events 31 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Parasthesia	2.7% 8/297 • Number of events 9 • Adverse event data was collected until 18-24 month visit.	4.6% 14/303 • Number of events 14 • Adverse event data was collected until 18-24 month visit.
General disorders Other	23.6% 70/297 • Number of events 105 • Adverse event data was collected until 18-24 month visit.	28.4% 86/303 • Number of events 111 • Adverse event data was collected until 18-24 month visit.

Additional Information

Bernard Bendok, MD

Mayo Clinic

Phone: 3129269441

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	HydroCoil Embolic System n=297 participants at risk Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950) HydroCoil Embolic System: HydroCoil Embolic System	Control n=303 participants at risk Aneurysm treatment using bare platinum coil(s) Control (bare platinum coils): bare platinum coils
Surgical and medical procedures Air embolism	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Altered mental status	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Amaurosis fugax	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Blood and lymphatic system disorders Anemia	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.66% 2/303 • Number of events 2 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Aneurysm, left ICA ophthalmic	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Vascular disorders Aortic dissection	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Respiratory, thoracic and mediastinal disorders Apnea	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Vascular disorders Arteriovenous fistula	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Cardiac disorders Arrythmia	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.66% 2/303 • Number of events 2 • Adverse event data was collected until 18-24 month visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Cardiac disorders Cardiac Arrest	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Cardiac disorders Cardiomyopathy, non-schemic	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Vascular disorders Carotid artery dissection	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.66% 2/303 • Number of events 2 • Adverse event data was collected until 18-24 month visit.
Renal and urinary disorders Cerebral salt wasting	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Surgical and medical procedures Coil herniation	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Surgical and medical procedures Coil prolapse	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Concussion	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Cardiac disorders Coronary artery disease	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Confusion	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Cranial nerve palsy	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Psychiatric disorders Depression	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Musculoskeletal and connective tissue disorders Fracture left-femur	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Surgical and medical procedures Groin hematoma	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Headache	1.3% 4/297 • Number of events 5 • Adverse event data was collected until 18-24 month visit.	1.7% 5/303 • Number of events 5 • Adverse event data was collected until 18-24 month visit.
Eye disorders Hemianopsia	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.66% 2/303 • Number of events 2 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Hemorrhage, intraventicular	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Hydrocephalus	2.7% 8/297 • Number of events 9 • Adverse event data was collected until 18-24 month visit.	1.3% 4/303 • Number of events 4 • Adverse event data was collected until 18-24 month visit.
Vascular disorders Hypertensive urgency	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Intracranial aneurysm, ruptured	1.0% 3/297 • Number of events 3 • Adverse event data was collected until 18-24 month visit.	2.0% 6/303 • Number of events 6 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Intracranial hemorrhage, non-specified	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Intracranial hemorrhage, subarachnoid	0.67% 2/297 • Number of events 2 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Intracranial, hemorrhage, subdural	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.66% 2/303 • Number of events 2 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Intracranial hypertension	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Infections and infestations Leukocytosis	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Loss of consciousness	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Memory loss	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Infections and infestations Meningitis	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Gastrointestinal disorders Nausea	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Paresis	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.66% 2/303 • Number of events 2 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Parasthesia	0.67% 2/297 • Number of events 2 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Cardiac disorders Pericardial effusion	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.67% 2/297 • Number of events 2 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 2 • Adverse event data was collected until 18-24 month visit.
Vascular disorders Psedudoaneurysm, cerebral	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.99% 3/303 • Number of events 3 • Adverse event data was collected until 18-24 month visit.
Vascular disorders Retroperitonial hemorrhage	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Eye disorders Scotoma	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Seizure	2.4% 7/297 • Number of events 9 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Infections and infestations Sepsis	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Stroke	5.1% 15/297 • Number of events 16 • Adverse event data was collected until 18-24 month visit.	3.6% 11/303 • Number of events 11 • Adverse event data was collected until 18-24 month visit.
Nervous system disorders Transient ischemic attach	0.00% 0/297 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Surgical and medical procedures Procedural Thrombosis	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Infections and infestations Urinary tract infection	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.
Vascular disorders Vasospasm	3.7% 11/297 • Number of events 16 • Adverse event data was collected until 18-24 month visit.	5.6% 17/303 • Number of events 19 • Adverse event data was collected until 18-24 month visit.
Ear and labyrinth disorders Vertigo	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.33% 1/303 • Number of events 1 • Adverse event data was collected until 18-24 month visit.
Eye disorders Visual disturbance	0.34% 1/297 • Number of events 1 • Adverse event data was collected until 18-24 month visit.	0.00% 0/303 • Adverse event data was collected until 18-24 month visit.