SHIELD: Pipeline Flex With SHield Technology Embolization - An International MulticEnter ObservationaL Post Market StuDy

• Sponsor: Medtronic Neurovascular Clinical Affairs (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02719522
• Collaborator: Medtronic Bakken Research Center (Industry)
• Enrollment: 205
• Locations: 21
• Actual Duration (Months): 41.7
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a prospective, single-arm, multi-center post-market observational study assessing the performance of the Pipeline™ Flex Embolization Device with Shield Technology™ in subjects undergoing treatment for intracranial aneurysms in a large real-world, post-market setting.

Condition or Disease	Intervention/Treatment	Phase
Intracranial Aneurysm	Device: Pipeline™ Flex Embolization Device with Shield Technology™

Detailed Description

Eligible subjects will be treated with the Pipeline™ Flex Embolization Device with Shield Technology™.

Subjects will undergo standard of care follow-up visits. Data generated per standard of care will be collected for 1 year beyond the index procedure.

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402 (j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402 (j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.)

Study Design

• Study Type: Observational
• Actual Enrollment: 205 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Pipeline Flex With SHield Technology Embolization - An International MulticEnter ObservationaL Post Market StuDy of Treated Intra Cranial Aneurysms (SHIELD)
• Actual Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Aug 22, 2019
• Actual Study Completion Date: Aug 22, 2019

Outcome Measures

Primary Outcome Measures

1. Safety - Stroke/Death Occurrence [1 year]

   Percentage (%) of Participants who experienced a major stroke in the territory supplied by the treated artery or neurological death post-procedure (1-year)

2. Effectiveness - Aneurysm Occlusion [1 year]

   Percentage (%) of Participants who have achieved complete aneurysm occlusion (defined as Raymond-Roy grade 1) without significant parent artery stenosis (≤ 50%) or retreatment of the target aneurysm post-procedure (1-year)

Secondary Outcome Measures

1. Safety - Stroke/Death Occurrence - 30 Days [30 days]

   Percentage (%) of Participants who experienced a major stroke in the territory supplied by the treated artery or neurological death at 30 days post-procedure due to procedural complications

2. Safety - Intracerebral Hemorrhage (ICH) [1 year]

   Percentage (%) of Participants who experienced a delayed intracerebral hemorrhage > 30 days post-procedure

3. Effectiveness - Deployment Rate [1 year]

   Percentage (%) of Participants who have had a successful deployment of the device at the target site. A device is considered properly deployed when it covers the entire length of the aneurysm neck.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subject has provided written Data Release Form (DRF) or informed consent using the Institutional Review Board (IRB)/ Ethic Committee (EC)-approved consent form and agrees to comply with protocol requirements.

• At least 18 years of age.

• Subject has already been selected for flow diversion therapy as the appropriate treatment.

• Subject has a target IA that has a parent vessel with diameter 1.5-5.0 mm distal/proximal to the target IA.

Exclusion Criteria:

• Major surgery including endovascular procedures within the past 30 days.

• Subject with target IA located in the basilar artery

• Subject with anatomy not appropriate for endovascular treatment due to severe intracranial vessel tortuosity or stenosis determined from baseline or pre-procedure imaging, or a history of intracranial vasospasm not responsive to medical therapy.

• Stent is in place in the parent artery at the target IA location.

• Subject with an acutely (within 30 days) ruptured aneurysm with a Hunt and Hess grade of 4 or higher.

• Any known contraindication to treatment with the Pipeline™ Flex Embolization Device with Shield Technology™ per Instructions for Use.

• The investigator determines that the health of the subject or the validity of the study outcomes (e.g., high risk of neurologic events, conditions that may increase the chance of stroke, worsening of clinical condition in the last 30 days) may be compromised by the subject's enrollment.

• Pregnant or breast-feeding women or women who wish to become pregnant during the length of study participation.

• Subject is currently enrolled or planning to participate in a potentially confounding drug or device trial during the course of this study. Co-enrollment in concurrent trials is only allowed when documented pre-approval is obtained from Medtronic.

• Legal incapacity or evidence that a subject cannot understand the purpose and risks of the study or inability to comply fully with study procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gold Coast University Hospital	Southport		Australia	QLD 4215
2	Rigshospitalet	Copenhagen		Denmark	2100
3	Turun Yliopistollinen keskussairaala	Turku		Finland
4	Hôpital Bicêtre	Le Kremlin-Bicêtre		France
5	Universitätsklinikum Augsburg	Augsburg		Germany
6	Charité Centrum	Berlin		Germany
7	Alfried Krupp Krankenhaus	Essen		Germany
8	Universitätsklinikums Heidelberg	Heidelberg		Germany
9	Universitätsklinikum des Saarlandes	Homburg		Germany
10	Hellenic Airforce Hospital	Athens		Greece
11	Országos Klinikai Idegtudományi Intézet	Budapest		Hungary
12	Hadassah Medical Organization	Jerusalem		Israel
13	Ospedale M. Bufalini	Cesena		Italy
14	Istituto Neurologico Carlo Besta	Milan		Italy
15	Hospital Universitario Cruces	Barakaldo		Spain
16	Hospital Fundación Jiménez Díaz	Madrid		Spain	28040
17	Hospital Universitario de la Princesa	Madrid		Spain
18	Hospital Universitario Puerta de Hierro	Madrid		Spain
19	Hospital Universitario Central de Asturias	Oviedo		Spain
20	Queen Elizabeth Hospital	Birmingham		United Kingdom	B15 2TH
21	Royal Preston Hospital	Preston		United Kingdom

Sponsors and Collaborators

• Medtronic Neurovascular Clinical Affairs
• Medtronic Bakken Research Center

Investigators

• Study Chair: Saleh Lamin, The Queen Elizabeth Hospital

Study Documents (Full-Text)

• Study Protocol - Jun 24, 2016
• Statistical Analysis Plan - Mar 12, 2019

More Information

Publications

• Becske T, Kallmes DF, Saatci I, McDougall CG, Szikora I, Lanzino G, Moran CJ, Woo HH, Lopes DK, Berez AL, Cher DJ, Siddiqui AH, Levy EI, Albuquerque FC, Fiorella DJ, Berentei Z, Marosfoi M, Cekirge SH, Nelson PK. Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology. 2013 Jun;267(3):858-68. doi: 10.1148/radiol.13120099. Epub 2013 Feb 15.
• Chitale R, Gonzalez LF, Randazzo C, Dumont AS, Tjoumakaris S, Rosenwasser R, Chalouhi N, Gordon D, Jabbour P. Single center experience with pipeline stent: feasibility, technique, and complications. Neurosurgery. 2012 Sep;71(3):679-91; discussion 691. doi: 10.1227/NEU.0b013e318260fe86.
• Kallmes DF, Hanel R, Lopes D, Boccardi E, Bonafé A, Cekirge S, Fiorella D, Jabbour P, Levy E, McDougall C, Siddiqui A, Szikora I, Woo H, Albuquerque F, Bozorgchami H, Dashti SR, Delgado Almandoz JE, Kelly ME, Turner R 4th, Woodward BK, Brinjikji W, Lanzino G, Lylyk P. International retrospective study of the pipeline embolization device: a multicenter aneurysm treatment study. AJNR Am J Neuroradiol. 2015 Jan;36(1):108-15. doi: 10.3174/ajnr.A4111. Epub 2014 Oct 29. Erratum in: AJNR Am J Neuroradiol. 2015 May;36(5):E39-40.
• Kan P, Siddiqui AH, Veznedaroglu E, Liebman KM, Binning MJ, Dumont TM, Ogilvy CS, Gaughen JR Jr, Mocco J, Velat GJ, Ringer AJ, Welch BG, Horowitz MB, Snyder KV, Hopkins LN, Levy EI. Early postmarket results after treatment of intracranial aneurysms with the pipeline embolization device: a U.S. multicenter experience. Neurosurgery. 2012 Dec;71(6):1080-7; discussion 1087-8. doi: 10.1227/NEU.0b013e31827060d9.
• McAuliffe W, Wycoco V, Rice H, Phatouros C, Singh TJ, Wenderoth J. Immediate and midterm results following treatment of unruptured intracranial aneurysms with the pipeline embolization device. AJNR Am J Neuroradiol. 2012 Jan;33(1):164-70. doi: 10.3174/ajnr.A2727. Epub 2011 Oct 6.
• Nelson PK, Lylyk P, Szikora I, Wetzel SG, Wanke I, Fiorella D. The pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol. 2011 Jan;32(1):34-40. doi: 10.3174/ajnr.A2421. Epub 2010 Dec 9.
• Saatci I, Yavuz K, Ozer C, Geyik S, Cekirge HS. Treatment of intracranial aneurysms using the pipeline flow-diverter embolization device: a single-center experience with long-term follow-up results. AJNR Am J Neuroradiol. 2012 Sep;33(8):1436-46. doi: 10.3174/ajnr.A3246. Epub 2012 Jul 19.
• Skukalek SL, Winkler AM, Kang J, Dion JE, Cawley CM, Webb A, Dannenbaum MJ, Schuette AJ, Asbury B, Tong FC. Effect of antiplatelet therapy and platelet function testing on hemorrhagic and thrombotic complications in patients with cerebral aneurysms treated with the pipeline embolization device: a review and meta-analysis. J Neurointerv Surg. 2016 Jan;8(1):58-65. doi: 10.1136/neurintsurg-2014-011145. Epub 2014 Nov 10. Review.
• Yu SC, Kwok CK, Cheng PW, Chan KY, Lau SS, Lui WM, Leung KM, Lee R, Cheng HK, Cheung YL, Chan CM, Wong GK, Hui JW, Wong YC, Tan CB, Poon WL, Pang KY, Wong AK, Fung KH. Intracranial aneurysms: midterm outcome of pipeline embolization device--a prospective study in 143 patients with 178 aneurysms. Radiology. 2012 Dec;265(3):893-901. doi: 10.1148/radiol.12120422. Epub 2012 Sep 20.

• Responsible Party: Medtronic Neurovascular Clinical Affairs
• ClinicalTrials.gov Identifier: NCT02719522
• Other Study ID Numbers: NV-PED-10
• First Posted: Mar 25, 2016
• Last Update Posted: Jan 11, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Additional relevant MeSH terms: Intracranial Aneurysm; Aneurysm

Study Results

Participant Flow

Recruitment Details	Patients have been enrolled in 21 sites in EU, Australia and Israel between 24-Mar-2016 and 27-Sep-2017.

Arm/Group Title	Intention to Treat (ITT)
Arm/Group Description	Includes all consented subjects in whom deployment of the Pipeline™ Shield device was attempted. For the ITT population, primary effectiveness endpoint analysis was based on Full Analysis Set (FAS) population and safety analysis was based on the ITT population.
Period Title: Overall Study
STARTED	204
COMPLETED	193
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Intention to Treat (ITT)
Arm/Group Description	Includes all consented subjects in whom deployment of the Pipeline™ Shield device was attempted. For the ITT population, primary effectiveness endpoint analysis was based on Full Analysis Set (FAS) population and safety analysis was based on the ITT population.
Overall Participants	204
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.8 (12.81)
Age, Customized (Count of Participants)
≤60 years	134 65.7%
> 60 years	70 34.3%
Sex: Female, Male (Count of Participants)
Female	166 81.4%
Male	38 18.6%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Greece	21 10.3%
Hungary	5 2.5%
Finland	9 4.4%
Denmark	3 1.5%
Italy	26 12.7%
United Kingdom	27 13.2%
Israel	5 2.5%
Australia	30 14.7%
France	1 0.5%
Germany	23 11.3%
Spain	54 26.5%

Outcome Measures

1. Primary Outcome

Title	Safety - Stroke/Death Occurrence
Description	Percentage (%) of Participants who experienced a major stroke in the territory supplied by the treated artery or neurological death post-procedure (1-year)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intention to Treat (ITT)
Arm/Group Description	Includes all consented subjects in whom deployment of the Pipeline™ Shield device was attempted. For the ITT population, primary effectiveness endpoint analysis was based on Full Analysis Set (FAS) population and safety analysis was based on the ITT population.
Measure Participants	204
Number (95% Confidence Interval) [percentage of patients with event]	3.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intention to Treat (ITT)
	Comments	The primary safety objective was to determine if the 2-sided 95% upper confidence interval of the primary safety endpoint was below the threshold of 15%. Missing safety data for subjects who were lost to FU without any evidence of a major stroke/death were imputed in the analysis using multiple imputation. Subjects who withdrew from the study prior to completion and had experienced a major stroke or death were counted towards the primary safety endpoint as having experienced the event.
	Type of Statistical Test	Superiority
	Comments	The primary safety objective was to determine if the 2-sided 95% upper confidence interval of the primary safety endpoint was below the threshold of 15%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Clopper-Pearson
	Comments

2. Primary Outcome

Title	Effectiveness - Aneurysm Occlusion
Description	Percentage (%) of Participants who have achieved complete aneurysm occlusion (defined as Raymond-Roy grade 1) without significant parent artery stenosis (≤ 50%) or retreatment of the target aneurysm post-procedure (1-year)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Primary effectiveness endpoint was analyzed specifically on subjects with successful device implantation (FAS population, N=200).

Arm/Group Title	Intention to Treat (ITT)
Arm/Group Description	Includes all consented subjects in whom deployment of the Pipeline™ Shield device was attempted. For the ITT population, primary effectiveness endpoint analysis was based on Full Analysis Set (FAS) population and safety analysis was based on the ITT population.
Measure Participants	200
Number (95% Confidence Interval) [percentage of patients]	71.67

3. Secondary Outcome

Title	Safety - Stroke/Death Occurrence - 30 Days
Description	Percentage (%) of Participants who experienced a major stroke in the territory supplied by the treated artery or neurological death at 30 days post-procedure due to procedural complications
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intention to Treat (ITT)
Arm/Group Description	Includes all consented subjects in whom deployment of the Pipeline™ Shield device was attempted. For the ITT population, primary effectiveness endpoint analysis was based on Full Analysis Set (FAS) population and safety analysis was based on the ITT population.
Measure Participants	204
Count of Participants [Participants]	6 2.9%

4. Secondary Outcome

Title	Safety - Intracerebral Hemorrhage (ICH)
Description	Percentage (%) of Participants who experienced a delayed intracerebral hemorrhage > 30 days post-procedure
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intention to Treat (ITT)
Arm/Group Description	Includes all consented subjects in whom deployment of the Pipeline™ Shield device was attempted. For the ITT population, primary effectiveness endpoint analysis was based on Full Analysis Set (FAS) population and safety analysis was based on the ITT population.
Measure Participants	204
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Effectiveness - Deployment Rate
Description	Percentage (%) of Participants who have had a successful deployment of the device at the target site. A device is considered properly deployed when it covers the entire length of the aneurysm neck.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intention to Treat (ITT)
Arm/Group Description	Includes all consented subjects in whom deployment of the Pipeline™ Shield device was attempted. For the ITT population, primary effectiveness endpoint analysis was based on Full Analysis Set (FAS) population and safety analysis was based on the ITT population.
Measure Participants	204
Count of Participants [Participants]	200 98%

Adverse Events

Time Frame	Adverse Events have been collected through 1 year from study procedure.
Arm/Group Title	Intention to Treat (ITT)
Arm/Group Description	Includes all consented subjects in whom deployment of the Pipeline™ Shield device was attempted. For the ITT population, primary effectiveness endpoint analysis was based on Full Analysis Set (FAS) population and safety analysis was based on the ITT population.
All Cause Mortality
	Intention to Treat (ITT)
	Affected / at Risk (%)	# Events
Total	2/204 (1%)
Serious Adverse Events
	Intention to Treat (ITT)
	Affected / at Risk (%)	# Events
Total	44/204 (21.6%)
Blood and lymphatic system disorders
Haemorrhagic diathesis	2/204 (1%)	2
Eye disorders
Retinal artery occlusion	1/204 (0.5%)	1
Visual impairment	1/204 (0.5%)	1
Gastrointestinal disorders
Gastric ulcer haemorrhage	1/204 (0.5%)	1
Retroperitoneal haemorrhage	1/204 (0.5%)	1
General disorders
Chest pain	1/204 (0.5%)	1
Pyrexia	1/204 (0.5%)	1
Infections and infestations
Haematoma infection	1/204 (0.5%)	1
Infection	1/204 (0.5%)	1
Staphylococcal sepsis	1/204 (0.5%)	1
Wound infection	1/204 (0.5%)	1
Injury, poisoning and procedural complications
Vascular procedure complication	1/204 (0.5%)	1
Femur fracture	1/204 (0.5%)	1
Intentional overdose	1/204 (0.5%)	1
Subarachnoid haemorrhage	1/204 (0.5%)	1
Vascular access site pseudoaneurysm	1/204 (0.5%)	1
Vascular pseudoaneurysm	3/204 (1.5%)	3
Metabolism and nutrition disorders
Hyperkalaemia	1/204 (0.5%)	1
Hyponatraemia	2/204 (1%)	2
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/204 (0.5%)	1
Nervous system disorders
Cerebral artery embolism	1/204 (0.5%)	1
Cerebral haemorrhage	2/204 (1%)	2
Cerebral infarction	2/204 (1%)	2
Cerebral microembolism	1/204 (0.5%)	1
Cerebrovascular accident	2/204 (1%)	2
Haemorrhagic stroke	1/204 (0.5%)	1
Intracranial mass	2/204 (1%)	2
Ischaemic cerebral infarction	1/204 (0.5%)	1
Ischaemic stroke	3/204 (1.5%)	3
VIth nerve paralysis	1/204 (0.5%)	1
Cerebral artery occlusion	1/204 (0.5%)	1
Cerebral vasoconstriction	1/204 (0.5%)	1
Cranial nerve palsies multiple	1/204 (0.5%)	1
Dysaesthesia	1/204 (0.5%)	1
Haemorrhage intracranial	2/204 (1%)	2
Haemorrhagic transformation stroke	1/204 (0.5%)	1
Headache	1/204 (0.5%)	1
Ruptured cerebral aneurysm	1/204 (0.5%)	1
Renal and urinary disorders
Renal failure	1/204 (0.5%)	1
Reproductive system and breast disorders
Vaginal haemorrhage	1/204 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Laryngospasm	1/204 (0.5%)	1
Pulmonary embolism	1/204 (0.5%)	1
Surgical and medical procedures
Aneurysm repair	3/204 (1.5%)	3
Vascular disorders
Embolism venous	1/204 (0.5%)	1
Vasospasm	1/204 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Intention to Treat (ITT)
	Affected / at Risk (%)	# Events
Total	74/204 (36.3%)
Blood and lymphatic system disorders
Haemorrhagic diathesis	1/204 (0.5%)	1
Increased tendency to bruise	1/204 (0.5%)	1
Eye disorders
Eye pain	1/204 (0.5%)	1
Photopsia	2/204 (1%)	2
Vision blurred	3/204 (1.5%)	3
Visual impairment	2/204 (1%)	2
Gastrointestinal disorders
Dyspepsia	1/204 (0.5%)	1
Mouth haemorrhage	1/204 (0.5%)	1
Nausea	1/204 (0.5%)	1
General disorders
Catheter site pain	1/204 (0.5%)	1
Vascular stent stenosis	16/204 (7.8%)	16
Injury, poisoning and procedural complications
Contusion	6/204 (2.9%)	6
Post procedural discomfort	1/204 (0.5%)	1
Post procedural haematuria	1/204 (0.5%)	1
Procedural headache	2/204 (1%)	2
Vascular access site haematoma	6/204 (2.9%)	6
Vascular access site haemorrhage	6/204 (2.9%)	6
Vascular access site pseudoaneurysm	3/204 (1.5%)	3
Vascular pseudoaneurysm	1/204 (0.5%)	1
Musculoskeletal and connective tissue disorders
Neck pain	1/204 (0.5%)	1
Nervous system disorders
Amnesia	1/204 (0.5%)	1
Carpal tunnel syndrome	1/204 (0.5%)	1
Cerebral artery occlusion	2/204 (1%)	2
Cerebral infarction	4/204 (2%)	4
Dysaesthesia	2/204 (1%)	2
Headache	11/204 (5.4%)	11
Hypoaesthesia	1/204 (0.5%)	1
Ischaemic cerebral infarction	1/204 (0.5%)	1
Lacunar infarction	1/204 (0.5%)	1
Nervous system disorder	1/204 (0.5%)	1
Paraesthesia	3/204 (1.5%)	3
Polyneuropathy	1/204 (0.5%)	1
Tension headache	1/204 (0.5%)	1
Transient ischaemic attack	1/204 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/204 (0.5%)	1
Bronchospasm	1/204 (0.5%)	1
Epistaxis	3/204 (1.5%)	3
Pharyngeal haematoma	1/204 (0.5%)	1
Vascular disorders
Haematoma	1/204 (0.5%)	1
Vascular wall hypertrophy	2/204 (1%)	2

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.