The Penumbra Liberty Trial: Safety and Effectiveness in the Treatment of Wide-Neck Intracranial Aneurysms

• Sponsor: Penumbra Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01636453
• Collaborator: (none)
• Enrollment: 120
• Locations: 3
• Arm: 1
• Duration (Months): 51
• Patients Per Site: 40
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

To assess the safety and effectiveness of the Penumbra Liberty Stent System as adjunctive treatment to embolic coils for wide-neck, saccular, intracranial aneurysms in the internal carotid artery (ICA). The Liberty Stent System is an implantable device comprised of a stent and delivery system designed as an adjunct to embolic coils in the treatment of wide-neck, saccular, intracranial aneurysms. It has three components: an implant, an introducer sheath and a delivery wire assembly. The implant component is made of superelastic and biocompatible nitinol tubular material. Patients presenting with wide-neck, saccular, intracranial aneurysms in the internal carotid artery (ICA) from the cavernous segment to the carotid terminus (including the paraclinoid, ophthalmic, hypophyseal and posterior communicating segments) will receive stent assisted coiling by the Penumbra Liberty Stent with any approved embolic coils currently on the market. Wide-neck aneurysms are defined by a neck ≥4mm or a dome-to-neck ratio <2. Each patient will be followed and assessed for 2, 6 and 12 months after enrollment.

Condition or Disease	Intervention/Treatment	Phase
Wide-neck, Saccular Intracranial Aneurysms	Device: Stent assisted coiling with the Liberty Stent	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Penumbra Liberty Trial: Safety and Effectiveness in the Treatment of Wide-Neck Intracranial Aneurysms
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liberty Stent arm Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months	Device: Stent assisted coiling with the Liberty Stent; Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Raymond Class I Complete Obliteration at 12 Months [At 12 months post-implant]

   Complete aneurysmal obliteration is defined by the method of Raymond et al. (Class I) (Stroke 2001;32:1998-2004).

2. Number of Neurological Deaths or Major Ipsilateral Strokes at 12 Months Post Treatment. [At 12 months post-implant]

Secondary Outcome Measures

1. Number of Ipsilateral Ischemic Strokes [At 12 months post-implant]

   Defined as episodes of focal or global neurological dysfunction due to brain or retinal infarction in the same hemisphere of the target aneurysm with signs and symptoms that persist for 24 hours or longer. When appropriate, non contrast CT scans will be used to eliminate hemorrhagic strokes

2. Number of Participants With Device-related Serious Adverse Events [During the procedure]

   The number of participants with device-related Serious Adverse Events as a measure of safety of the procedure and device. The FDA definitions for Serious Adverse Events are used.

3. Number of Device Deployment Failures [During the procedure]

   Defined by the failure of the device to deploy or failure to correctly position the device over the aneurysm

4. Number of Device Migrations [12 months post-implant]

   Migration is defined as movement of the Liberty stent by more than 5 mm as documented by the 12 month angiogram when compared to its immediate post-implant position.

5. Number of Participants With Aneurysm Raymond Class I Occlusion Grading [At 12 months post-implant]

   Raymond Class I Occlusion grading defined as complete obliteration of the aneurysm at 12 months.

6. Number of Intracranial Hemorrhages [At 12 months post-implant]

   Inclusive of subarachnoid, intraventricular or intraparenchymal hemorrhages (symptomatic or asymptomatic). Symptomatic is defined as a 4 point or more increase in the National Institutes of Health Stroke Scale (NIHSS) from baseline. The NIHSS ranges from 1 to 42, with higher scores indicating greater severity of stroke.

7. Number of Participants With Functional Outcome as Defined by the Modified Rankin Scale (mRS) 0-2 [At 12 months post-implant]

   The Modified Rankin Scale measures functional ability on a scale from 0-5, with 0 indicating no symptoms at all and 5 indicating severe disability.

8. All Cause Mortality (Number of Deaths From Any Cause) [At 12 months post-implant]

9. Number of Retreatments [At 12 months post-implant]

   Defined as any intervention after the completion of the initial stent assisted coiling procedure

10. Number of Participants Who Experienced Device Patency [at 12 months post-implant]

    Device patency (stenosis) at 12 months

11. Number of Participants Who Experienced Aneurysm Recanalization [At 12 months post-implant]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• At least 18 years old

• A wide-neck intracranial saccular aneurysm with a neck ≥ 4mm or a dome to neck ratio <2 in the ICA from the cavernous segment to the carotid terminus (including the paraclinoid, ophthalmic, hypophyseal and posterior communicating segments)

• Life expectancy > 12 months

• Signed Informed Consent

Exclusion Criteria:

• Females who are pregnant or intend to become pregnant during the study. (Females of child-bearing potential must have a urinary pregnancy test within 7 days of enrollment)

• Extradural aneurysms

• Known multiple untreated cerebral aneurysms at study entry

• Recent history of subarachnoid hemorrhage, intracranial hemorrhage, or major surgery within one month of enrollment

• Admission platelet <50,000 or any known hemorrhagic diathesis, coagulation deficiency, or on oral anticoagulant therapy with an INR >3.0

• Contraindication to angiography such as elevated creatinine or known allergy to angiographic contrast

• Contraindication to CT and/or MRI scans

• Known allergy to the metal component of the Penumbra Liberty Stent System

• Evidence of active infection (WBC >10x109 /L)

• Any medical conditions that will not allow the necessary follow-up for this study (e.g., pre-existing neurological or psychiatric diseases)

• Current substance-abuse /illicit drug use

• Angiographic evidence of an arterial stenosis proximal to the target lesion that could prevent device deployment

• Contraindications to study medications (heparin, aspirin, clopidogrel, and radiographic contrasts)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Swedish Medical Center	Denver	Colorado	United States	80112
2	Rush University Medical Center	Chicago	Illinois	United States	60612
3	Stony Brook University Medical Center	Stony Brook	New York	United States	11794-8122

Sponsors and Collaborators

• Penumbra Inc.

Investigators

• Principal Investigator: Demtrius Lopes, MD, Rush University Medical Center
• Principal Investigator: Henry Woo, MD, Stony Brook University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Penumbra Inc.
• ClinicalTrials.gov Identifier: NCT01636453
• Other Study ID Numbers: CLP 5038 (IDE # G120050)
• First Posted: Jul 10, 2012
• Last Update Posted: Aug 23, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Penumbra Inc.: wide-neck; saccular; intracranial aneurysms; ICA; Stent assisted coiling; Liberty Stent
• Additional relevant MeSH terms: Intracranial Aneurysm; Aneurysm

Study Results

Participant Flow

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Period Title: Overall Study
STARTED	120
COMPLETED	112
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Overall Participants	112
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	78 69.6%
>=65 years	34 30.4%
Sex: Female, Male (Count of Participants)
Female	100 89.3%
Male	12 10.7%
Race/Ethnicity, Customized (Count of Participants)
Asian	27 24.1%
Black	17 15.2%
Caucasian	61 54.5%
American Indian	1 0.9%
Other	2 1.8%
Unknown	4 3.6%
Region of Enrollment (participants) [Number]
United States	95 84.8%
Japan	25 22.3%
BMI (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	26.9

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Raymond Class I Complete Obliteration at 12 Months
Description	Complete aneurysmal obliteration is defined by the method of Raymond et al. (Class I) (Stroke 2001;32:1998-2004).
Time Frame	At 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	109
Count of Participants [Participants]	98 87.5%

2. Primary Outcome

Title	Number of Neurological Deaths or Major Ipsilateral Strokes at 12 Months Post Treatment.
Time Frame	At 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	112
Count of Participants [Participants]	3 2.7%

3. Secondary Outcome

Title	Number of Ipsilateral Ischemic Strokes
Description	Defined as episodes of focal or global neurological dysfunction due to brain or retinal infarction in the same hemisphere of the target aneurysm with signs and symptoms that persist for 24 hours or longer. When appropriate, non contrast CT scans will be used to eliminate hemorrhagic strokes
Time Frame	At 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	112
Number [participants]	8 7.1%

4. Secondary Outcome

Title	Number of Participants With Device-related Serious Adverse Events
Description	The number of participants with device-related Serious Adverse Events as a measure of safety of the procedure and device. The FDA definitions for Serious Adverse Events are used.
Time Frame	During the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	112
Count of Participants [Participants]	17 15.2%

5. Secondary Outcome

Title	Number of Device Deployment Failures
Description	Defined by the failure of the device to deploy or failure to correctly position the device over the aneurysm
Time Frame	During the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	112
Count of Participants [Participants]	5 4.5%

6. Secondary Outcome

Title	Number of Device Migrations
Description	Migration is defined as movement of the Liberty stent by more than 5 mm as documented by the 12 month angiogram when compared to its immediate post-implant position.
Time Frame	12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	105
Count of Participants [Participants]	0 0%

7. Secondary Outcome

Title	Number of Participants With Aneurysm Raymond Class I Occlusion Grading
Description	Raymond Class I Occlusion grading defined as complete obliteration of the aneurysm at 12 months.
Time Frame	At 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	109
Count of Participants [Participants]	99 88.4%

8. Secondary Outcome

Title	Number of Intracranial Hemorrhages
Description	Inclusive of subarachnoid, intraventricular or intraparenchymal hemorrhages (symptomatic or asymptomatic). Symptomatic is defined as a 4 point or more increase in the National Institutes of Health Stroke Scale (NIHSS) from baseline. The NIHSS ranges from 1 to 42, with higher scores indicating greater severity of stroke.
Time Frame	At 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	112
Count of Participants [Participants]	2 1.8%

9. Secondary Outcome

Title	Number of Participants With Functional Outcome as Defined by the Modified Rankin Scale (mRS) 0-2
Description	The Modified Rankin Scale measures functional ability on a scale from 0-5, with 0 indicating no symptoms at all and 5 indicating severe disability.
Time Frame	At 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	107
Count of Participants [Participants]	106 94.6%

10. Secondary Outcome

Title	All Cause Mortality (Number of Deaths From Any Cause)
Time Frame	At 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	112
Count of Participants [Participants]	0 0%

11. Secondary Outcome

Title	Number of Retreatments
Description	Defined as any intervention after the completion of the initial stent assisted coiling procedure
Time Frame	At 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	112
Count of Participants [Participants]	4 3.6%

12. Secondary Outcome

Title	Number of Participants Who Experienced Device Patency
Description	Device patency (stenosis) at 12 months
Time Frame	at 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	105
Count of Participants [Participants]	2 1.8%

13. Secondary Outcome

Title	Number of Participants Who Experienced Aneurysm Recanalization
Time Frame	At 12 months post-implant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
Measure Participants	112
Count of Participants [Participants]	6 5.4%

Adverse Events

Arm/Group Title	Liberty Stent Arm
Arm/Group Description	Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months Stent assisted coiling with the Liberty Stent: Patients are implanted with the Liberty Stent as an assist to embolic coiling of their wide-neck, saccular, intracranial aneurysms and follow for 12 months
All Cause Mortality
	Liberty Stent Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Liberty Stent Arm
	Affected / at Risk (%)	# Events
Total	34/112 (30.4%)
Blood and lymphatic system disorders
Blood and Lymphatic System Disorders	2/112 (1.8%)
Cardiac disorders
Cardiac Disorders	3/112 (2.7%)
Eye disorders
Eye Disorders	2/112 (1.8%)
Gastrointestinal disorders
Gastrointestinal Disorders	6/112 (5.4%)
General disorders
General Disorders	6/112 (5.4%)
Hepatobiliary disorders
Hepatobiliary Disorders	1/112 (0.9%)
Infections and infestations
Infections and Infestations	7/112 (6.3%)
Injury, poisoning and procedural complications
Injury, Poisoning and Procedural Complications	3/112 (2.7%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	1/112 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms, benign, malignant and unspecified	2/112 (1.8%)
Nervous system disorders
Nervous System Disorders	19/112 (17%)
Psychiatric disorders
Psychiatric Disorders	1/112 (0.9%)
Respiratory, thoracic and mediastinal disorders
Respiratory, Thoracic, and mediastinal disorders	1/112 (0.9%)
Vascular disorders
Vascular Disorders	2/112 (1.8%)
Other (Not Including Serious) Adverse Events
	Liberty Stent Arm
	Affected / at Risk (%)	# Events
Total	96/112 (85.7%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	6/112 (5.4%)
Cardiac disorders
Cardiac disorders	6/112 (5.4%)
Ear and labyrinth disorders
Ear and labyrinth disorders	4/112 (3.6%)
Endocrine disorders
Endrocrine disorders	1/112 (0.9%)
Eye disorders
Eye Disorders	34/112 (30.4%)
General disorders
General Disorders	23/112 (20.5%)
Immune system disorders
Immune System Disorders	6/112 (5.4%)
Infections and infestations
Infections and Infestations	22/112 (19.6%)
Injury, poisoning and procedural complications
Injury, poisoning, and procedural complications	11/112 (9.8%)
Investigations
Investigations	2/112 (1.8%)
Metabolism and nutrition disorders
Metabolism and nutrition disorders	6/112 (5.4%)
Musculoskeletal and connective tissue disorders
Muskuloskeletal and connective tissue disorders	10/112 (8.9%)
Nervous system disorders
Nervous System Disorders	60/112 (53.6%)
Psychiatric disorders
Psychiatric Disorders	1/112 (0.9%)
Renal and urinary disorders
Renal and urinary disorders	6/112 (5.4%)
Reproductive system and breast disorders
Reproductive system and breast disorders	2/112 (1.8%)
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	9/112 (8%)
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	12/112 (10.7%)
Surgical and medical procedures
Surgical and Medical Procedures	1/112 (0.9%)
Vascular disorders
Vascular Disorders	15/112 (13.4%)

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.