Pivotal Study of the FRED Stent System in the Treatment of Intracranial Aneurysms

• Sponsor: Microvention-Terumo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01801007
• Collaborator: (none)
• Enrollment: 145
• Locations: 24
• Arm: 1
• Duration (Months): 54
• Patients Per Site: 6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of the MicroVention Flow Redirection Intraluminal Device (FRED) system when used in the treatment of wide-necked intracranial aneurysms.

Condition or Disease	Intervention/Treatment	Phase
Intracranial Aneurysms	Device: Flow Re-Direction Endoluminal Device (FRED)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 145 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: FREDFRED
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pivotal Study of the MicroVention Flow Re-Direction Endoluminal Device (FRED) Stent System in the Treatment of Intracranial Aneurysms
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Jan 1, 2018
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Flow Re-Direction Endoluminal Device	Device: Flow Re-Direction Endoluminal Device (FRED)

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Complete Occlusion of the Target Aneurysm and ≤50% Stenosis of the Parent Artery and an Alternative Treatment of the Target Intracranial Aneurysm (IA) Had Not Been Performed Within 12 Months [12 months]

   The primary effectiveness endpoint has three components: 1) complete occlusion of the target aneurysm assessed by a core laboratory utilizing the Raymond-Roy Scale 2) ≤ 50% stenosis of the parent artery at the target (IA) using the Warfarin-Aspirin Symptomatic Intracranial Disease(WASID) criterion which is defined as greater than 50% luminal loss, 3) alternative treatment of the target IA is defined as re-treatment of the target aneurysm with an alternative treatment modality including open repair, endovascular placement of an additional stent or treatment of In-stent Stenosis observed. The Raymond-Roy Occlusion Classification has 3 responses, where Grade I is complete occlusion, no flow of contrast seen in the sac, Grade II is partial occlusion, some flow in the neck or sac, and Grade III is incomplete occlusion, apparent flow into the sac. Grade 1 indicates the best outcome.

2. Percentage of Participants Who Experience Neurological Death or Major Ipsilateral Stroke Measured by the Modified Rankin Scale (mRS) and the National Institute of Health Stroke Scale (NIHSS) [12 months]

   A major stroke is defined as a new neurological event that persists for > 24 hours and results in a ≥ 4 points increase in the NIHSS score compared to baseline or compared to any subsequent lower score. A major ipsilateral stroke is defined as that occurring within the vascular distribution of the stented artery. Neurologic death is defined as a death which has been adjudicated by the independent clinical events committee to have directly resulted from a neurologic cause.The NIHSS score ranges from 0 (no stroke symptoms) to 42 (severe stroke). mRS is 6 point assessment scale used to assess disability in patients who have suffered a stroke and is compared over time to check for recovery and degree of continued disability. The mRS score ranges from 0 (no disability) to 6 (death).

Secondary Outcome Measures

1. Percentage of Participants With Complete Occlusion of the Target Aneurysm on 12-month Angiography (Raymond-Roy 1) [12 months]

   Complete occlusion of the target aneurysm assessed by a core laboratory. The Raymond-Roy class is an angiographic classification scheme for grading the occlusion (closure) of endovascularly treated intracranial aneurysms: class I: complete obliteration, class II: residual neck, class III: residual aneurysm.

2. Percentage of Participants With ≥ 50% In-Stent Stenosis (ISS) at the Target Intracranial Aneurysm (IA) at 12 Months as Assessed by Angiography at the Independent Core Laboratory [12 months]

   Stenosis of the parent artery at the target IA using the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) criterion which is defined as greater than 50% luminal loss

3. Percentage of Participants in Whom an Unplanned Alternative Treatment of the Target IA Had Not Been Performed Within 12 Months [12 months]

   Re-treatment of the target aneurysm with an alternative treatment modality including open repair, endovascular placement of an additional stent or treatment of In-stent Stenosis observed

4. Percentage of Participants With Clinically Acceptable (90-100%) Occlusion of the Target Aneurysm, ≤ 50% Stenosis of the Parent Artery at the Target IA, and an Unplanned Alternative Treatment of the Target IA Had Not Been Performed [12 months]

   This endpoint has three components: 1) clinically acceptable occlusion of the target aneurysm assessed by a core laboratory as percent occlusion (90%-100%) 2) ≤ 50% stenosis of the parent artery at the target IA using the WASID criterion which is defined as greater than 50% luminal loss, 3) alternative treatment of the target IA is defined as re-treatment of the target aneurysm with an alternative treatment modality including open repair, endovascular placement of an additional stent or treatment of In-stent Stenosis observed. The Raymond-Roy scale has 3 responses, where Grade I is complete occlusion, no flow of contrast seen in the sac, Grade II is partial occlusion, some flow in the neck or sac, and Grade III is incomplete occlusion, apparent flow into the sac.

5. Percentage of Participants With Unsuccessful Delivery of the FRED [Index Procedure]

   Inability to deliver a FRED device to the target location

6. Percentage of Participants That Had Procedure Related Serious Adverse Events With the FRED System [12 months]

   A serious adverse event is any medical experience regardless of its relationship to the study treatment that occurs during participant enrollment in this trial that results in any of the following: (1) inpatient hospitalization or prolongation of a hospitalization; (b) persistent or significant disability or incapacity; (c) death of the study participant, or (d) necessitates an intervention to prevent a permanent impairment of a body function or permanent damage to a body structure. Procedure related events were associated with the index procedure, antiplatelet therapy, or follow up angiography.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant whose age ≥ 22 and ≤75 years

• Participant has single target aneurysm located in the internal carotid artery

• Participant sign and date an IRB/EC approved informed consent prior initiation of any study procedures

Exclusion Criteria:

• Participant who suffers from an intracranial hemorrhage in the last 30 days

• Participant who suffers from a subarachnoid hemorrhage in the last 60 days

• Participant with symptomatic extracranial mass or currently undergoing radiation therapy for tumor of the head and neck region

• Participant who is pregnant or breastfeeding

• Participant has an arteriovenous malformation (AVM) in the area of the target aneurysm

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
2	Swedish Medical Center / RIA	Englewood	Colorado	United States	80113
3	Lyerly Neurosurgery	Jacksonville	Florida	United States	32207
4	Emory University	Atlanta	Georgia	United States	30322
5	Northwestern University	Chicago	Illinois	United States	60611
6	Rush University Medical Center	Chicago	Illinois	United States	60612
7	Norton Neuroscience Institute	Louisville	Kentucky	United States	40202
8	The Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
9	Tufts Medical Center	Boston	Massachusetts	United States	02111
10	Abbott Northwestern Hospital	Minneapolis	Minnesota	United States	55407
11	Mayo Clinic	Rochester	Minnesota	United States	55903
12	Washington University	Saint Louis	Missouri	United States	63110
13	Capital Health Hospital	Trenton	New Jersey	United States	08638
14	Albany Medical Center	Albany	New York	United States	12208
15	University at Buffalo	Buffalo	New York	United States	14203
16	North Shore University Hospital	Manhasset	New York	United States	11030
17	Mount Sinai Health System	New York	New York	United States	10019
18	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
19	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
20	Medical University of South Carolina	Charleston	South Carolina	United States	29425
21	Methodist University Hospital	Memphis	Tennessee	United States	38104
22	Baylor Saint Luke Medical Center	Houston	Texas	United States	77030
23	The Methodist Hospital	Houston	Texas	United States	77030
24	Institute of Biomedical Research and Innovation	Kobe		Japan	650-0047

Sponsors and Collaborators

• Microvention-Terumo, Inc.

Investigators

• Principal Investigator: Cameron McDougall, MD, Johns Hopkins University

Study Documents (Full-Text)

• Statistical Analysis Plan - Jul 13, 2018
• Study Protocol - Nov 14, 2016

More Information

Publications

None provided.

• Responsible Party: Microvention-Terumo, Inc.
• ClinicalTrials.gov Identifier: NCT01801007
• Other Study ID Numbers: CL12001; G120111
• First Posted: Feb 28, 2013
• Last Update Posted: Mar 8, 2021
• Last Verified: Feb 1, 2021

• Additional relevant MeSH terms: Intracranial Aneurysm; Aneurysm

Study Results

Participant Flow

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Period Title: Overall Study
STARTED	145
COMPLETED	134
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Overall Participants	145
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (11.5)
Sex: Female, Male (Count of Participants)
Female	129 89%
Male	16 11%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 13.1%
Not Hispanic or Latino	126 86.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%
Asian	7 4.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	24 16.6%
White	104 71.7%
More than one race	0 0%
Unknown or Not Reported	9 6.2%
Region of Enrollment (Count of Participants)
United States	139 95.9%
Japan	6 4.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Occlusion of the Target Aneurysm and ≤50% Stenosis of the Parent Artery and an Alternative Treatment of the Target Intracranial Aneurysm (IA) Had Not Been Performed Within 12 Months
Description	The primary effectiveness endpoint has three components: 1) complete occlusion of the target aneurysm assessed by a core laboratory utilizing the Raymond-Roy Scale 2) ≤ 50% stenosis of the parent artery at the target (IA) using the Warfarin-Aspirin Symptomatic Intracranial Disease(WASID) criterion which is defined as greater than 50% luminal loss, 3) alternative treatment of the target IA is defined as re-treatment of the target aneurysm with an alternative treatment modality including open repair, endovascular placement of an additional stent or treatment of In-stent Stenosis observed. The Raymond-Roy Occlusion Classification has 3 responses, where Grade I is complete occlusion, no flow of contrast seen in the sac, Grade II is partial occlusion, some flow in the neck or sac, and Grade III is incomplete occlusion, apparent flow into the sac. Grade 1 indicates the best outcome.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Participants that had 12 month angiographic assessment of vessel stenosis

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Measure Participants	139
Number [percentage of participants]	57.0 39.3%

2. Primary Outcome

Title	Percentage of Participants Who Experience Neurological Death or Major Ipsilateral Stroke Measured by the Modified Rankin Scale (mRS) and the National Institute of Health Stroke Scale (NIHSS)
Description	A major stroke is defined as a new neurological event that persists for > 24 hours and results in a ≥ 4 points increase in the NIHSS score compared to baseline or compared to any subsequent lower score. A major ipsilateral stroke is defined as that occurring within the vascular distribution of the stented artery. Neurologic death is defined as a death which has been adjudicated by the independent clinical events committee to have directly resulted from a neurologic cause.The NIHSS score ranges from 0 (no stroke symptoms) to 42 (severe stroke). mRS is 6 point assessment scale used to assess disability in patients who have suffered a stroke and is compared over time to check for recovery and degree of continued disability. The mRS score ranges from 0 (no disability) to 6 (death).
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Measure Participants	145
Count of Participants [Participants]	9 6.2%

3. Secondary Outcome

Title	Percentage of Participants With Complete Occlusion of the Target Aneurysm on 12-month Angiography (Raymond-Roy 1)
Description	Complete occlusion of the target aneurysm assessed by a core laboratory. The Raymond-Roy class is an angiographic classification scheme for grading the occlusion (closure) of endovascularly treated intracranial aneurysms: class I: complete obliteration, class II: residual neck, class III: residual aneurysm.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Participants that had 12 month angiographic assessment of aneurysm occlusion and vessel stenosis.

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Measure Participants	140
Count of Participants [Participants]	88 60.7%

4. Secondary Outcome

Title	Percentage of Participants With ≥ 50% In-Stent Stenosis (ISS) at the Target Intracranial Aneurysm (IA) at 12 Months as Assessed by Angiography at the Independent Core Laboratory
Description	Stenosis of the parent artery at the target IA using the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) criterion which is defined as greater than 50% luminal loss
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Participants that had 12 month angiographic assessment of vessel stenosis.

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Measure Participants	139
Count of Participants [Participants]	6 4.1%

5. Secondary Outcome

Title	Percentage of Participants in Whom an Unplanned Alternative Treatment of the Target IA Had Not Been Performed Within 12 Months
Description	Re-treatment of the target aneurysm with an alternative treatment modality including open repair, endovascular placement of an additional stent or treatment of In-stent Stenosis observed
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Participants that had 12 months angiographic assessment and vessel stenosis.

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Measure Participants	140
Count of Participants [Participants]	132 91%

6. Secondary Outcome

Title	Percentage of Participants With Clinically Acceptable (90-100%) Occlusion of the Target Aneurysm, ≤ 50% Stenosis of the Parent Artery at the Target IA, and an Unplanned Alternative Treatment of the Target IA Had Not Been Performed
Description	This endpoint has three components: 1) clinically acceptable occlusion of the target aneurysm assessed by a core laboratory as percent occlusion (90%-100%) 2) ≤ 50% stenosis of the parent artery at the target IA using the WASID criterion which is defined as greater than 50% luminal loss, 3) alternative treatment of the target IA is defined as re-treatment of the target aneurysm with an alternative treatment modality including open repair, endovascular placement of an additional stent or treatment of In-stent Stenosis observed. The Raymond-Roy scale has 3 responses, where Grade I is complete occlusion, no flow of contrast seen in the sac, Grade II is partial occlusion, some flow in the neck or sac, and Grade III is incomplete occlusion, apparent flow into the sac.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Participants that had 12 month angiographic assessment of vessel stenosis.

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Measure Participants	139
Count of Participants [Participants]	100 69%

7. Secondary Outcome

Title	Percentage of Participants With Unsuccessful Delivery of the FRED
Description	Inability to deliver a FRED device to the target location
Time Frame	Index Procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Measure Participants	145
Count of Participants [Participants]	2 1.4%

8. Secondary Outcome

Title	Percentage of Participants That Had Procedure Related Serious Adverse Events With the FRED System
Description	A serious adverse event is any medical experience regardless of its relationship to the study treatment that occurs during participant enrollment in this trial that results in any of the following: (1) inpatient hospitalization or prolongation of a hospitalization; (b) persistent or significant disability or incapacity; (c) death of the study participant, or (d) necessitates an intervention to prevent a permanent impairment of a body function or permanent damage to a body structure. Procedure related events were associated with the index procedure, antiplatelet therapy, or follow up angiography.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
Measure Participants	145
Count of Participants [Participants]	40 27.6%

Adverse Events

Time Frame	12 months
Arm/Group Title	Flow Re-Direction Endoluminal Device
Arm/Group Description	The FRED Stent System is intended to be used in the treatment of wide-necked Intracranial Aneurysms.
All Cause Mortality
	Flow Re-Direction Endoluminal Device
	Affected / at Risk (%)	# Events
Total	2/145 (1.4%)
Serious Adverse Events
	Flow Re-Direction Endoluminal Device
	Affected / at Risk (%)	# Events
Total	63/145 (43.4%)
Blood and lymphatic system disorders
Anemia	1/145 (0.7%)	1
Cardiac disorders
Arrhythmia	2/145 (1.4%)	3
Eye disorders
Visual impairment	2/145 (1.4%)	2
Vision blurred	1/145 (0.7%)	1
Gastrointestinal disorders
Gastric haemorrhage	1/145 (0.7%)	1
Gastric perforation	1/145 (0.7%)	1
Gastrointestinal haemorrhage	1/145 (0.7%)	1
Pancreatitis	1/145 (0.7%)	1
Retroperitoneal haematoma	1/145 (0.7%)	1
Small intestinal obstruction	1/145 (0.7%)	1
General disorders
Chest pain	1/145 (0.7%)	1
Device deployment issue	1/145 (0.7%)	1
Device dislocation	1/145 (0.7%)	1
Device failure	6/145 (4.1%)	6
Device malfunction	1/145 (0.7%)	1
Device occlusion	1/145 (0.7%)	1
In-stent cerebral artery stenosis	1/145 (0.7%)	1
Puncture site haemorrhage	1/145 (0.7%)	1
Thrombosis in device	10/145 (6.9%)	10
Infections and infestations
Abdominal abscess	1/145 (0.7%)	1
Appendicitis	1/145 (0.7%)	1
Cellulitis	1/145 (0.7%)	1
Cellulitis staphylococcal	1/145 (0.7%)	1
Endocarditis	1/145 (0.7%)	1
Pneumonia	2/145 (1.4%)	2
Sepsis	1/145 (0.7%)	1
Urinary tract infection	2/145 (1.4%)	2
Injury, poisoning and procedural complications
Gastrointestinal anastomotic leak	1/145 (0.7%)	1
Head injury	1/145 (0.7%)	1
Vascular pseudoaneurysm	1/145 (0.7%)	1
Investigations
Visual field tests abnormal	1/145 (0.7%)	1
Metabolism and nutrition disorders
Dehydration	1/145 (0.7%)	1
Musculoskeletal and connective tissue disorders
Exostosis	1/145 (0.7%)	1
Muscular weakness	2/145 (1.4%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/145 (0.7%)	1
Large cell lung cancer metastatic	1/145 (0.7%)	1
Nervous system disorders
Blindness	1/145 (0.7%)	1
Cerebral haemorrhage	3/145 (2.1%)	3
Cerebral hypoperfusion	1/145 (0.7%)	1
Cerebrovascular accident	6/145 (4.1%)	6
Encephalopathy	1/145 (0.7%)	1
Eyelid ptosis	1/145 (0.7%)	1
Generalised tonic-clonic seizure	1/145 (0.7%)	1
Headache	1/145 (0.7%)	1
Hydrocephalus	1/145 (0.7%)	1
Intracranial pressure increased	1/145 (0.7%)	1
Ischaemic stroke	4/145 (2.8%)	4
Mental impairment	1/145 (0.7%)	1
Paraesthesia	1/145 (0.7%)	1
Posterior reversible encephalopathy syndrome	1/145 (0.7%)	1
Radiculitis	1/145 (0.7%)	1
Seizure	2/145 (1.4%)	2
Transient ischaemic attack	5/145 (3.4%)	5
Psychiatric disorders
Delirium	1/145 (0.7%)	1
Depression	1/145 (0.7%)	1
Renal and urinary disorders
Acute kidney injury	1/145 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/145 (0.7%)	1
Atelectasis	1/145 (0.7%)	1
Pneumonia aspiration	1/145 (0.7%)	1
Pulmonary embolism	2/145 (1.4%)	2
Pulmonary oedema	1/145 (0.7%)	1
Respiratory failure	1/145 (0.7%)	1
Surgical and medical procedures
Aneurysm repair	11/145 (7.6%)	11
Angioplasty	1/145 (0.7%)	1
Stent placement	1/145 (0.7%)	1
Vascular disorders
Aneurysm	1/145 (0.7%)	1
Arterial stenosis	1/145 (0.7%)	1
Carotid artery stenosis	1/145 (0.7%)	1
Cerebral vasoconstriction	1/145 (0.7%)	1
Deep vein thrombosis	1/145 (0.7%)	1
Femoral artery occlusion	1/145 (0.7%)	1
Haematoma	1/145 (0.7%)	1
Vascular wall hypertrophy	1/145 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Flow Re-Direction Endoluminal Device
	Affected / at Risk (%)	# Events
Total	61/145 (42.1%)
Eye disorders
Visual impairment	11/145 (7.6%)	16
Infections and infestations
Urinary tract infection	9/145 (6.2%)	9
Nervous system disorders
Headache	43/145 (29.7%)	45
Vascular disorders
Haematoma	9/145 (6.2%)	9
Vasospasm	16/145 (11%)	17

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Investigators must inform and submit to sponsor all manuscripts or abstracts at least 30 days prior to submitting the proposed Publication to a publisher or other third party.