Prospective Study on Embolization of Intracranial Aneurysms With Pipeline™ Embolization Device (PREMIER)

Prospective Study on Embolization of Intracranial Aneurysms With the Pipeline™ Device (PREMIER)

The purpose of this study is to assess the safety and effectiveness of the Pipeline™ device in the treatment of unruptured, wide-neck intracranial aneurysms.

Study Overview

• Status: Completed
• Conditions: Intracranial Aneurysm
• Intervention / Treatment: Device: Pipeline™ Embolization Device/ Pipeline™Flex Embolization Device

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
• United States
  • Colorado
    • Englewood, Colorado, United States, 80112
      • Radiology Imaging Associates
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Medical Center Jacksonville
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
    • Winter Park, Florida, United States, 32789
      • Florida Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Physicians Lexington
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts University Medical Center
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New York
    • Buffalo, New York, United States, 14203
      • Kaleida Health/University of Buffalo
    • Stony Brook, New York, United States, 11794
      • Stony Brook University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • The Methodist Hospital
    • Houston, Texas, United States, 77030
      • St. Luke's Health Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has provided written informed consent using the IRB/EC-approved consent form and agrees to comply with protocol requirements.
2. Age 22-80 years.

3. Subject has a target intracranial aneurysm (IA) located in the:

   1. Internal carotid artery (up to the carotid terminus) OR
   2. Vertebral artery segment up to and including the posterior inferior cerebellar artery
4. Subject has a target IA that is ≤ 12 mm.
5. Subject has a target IA that has a parent vessel with diameter 1.5-5.0 mm distal/proximal to the target IA.
6. Subject has a target IA with an aneurysm neck ≥ 4mm or a dome to neck ratio ≤ 1.5.
7. Subject has a pre-procedure PRU value between 60-200.

Exclusion Criteria:

1. Subject has received an intracranial implant (e.g. coils) in the area of the target IA within the past 12 weeks.
2. Subarachnoid hemorrhage in the past 30 days.
3. 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.
4. Major surgery in the last 30 days.
5. History of irreversible bleeding disorder and/or subject presents with signs of active bleeding.

6. Any known contraindication to treatment with the Pipeline™ device, including:

   1. Stent is in place in the parent artery at the target IA location
   2. Contraindication to dual antiplatelet therapy
   3. Relative contraindication to angiography (e.g., serum creatinine >2.5 mg/dL, allergy to contrast that cannot be medically controlled).
   4. Known severe allergy to platinum or cobalt/chromium alloys.
   5. Evidence of active infection at the time of treatment (e.g., fever with temperature >38°C and/or WBC >1.5 109/L).
7. The Investigator determines that the health of the subject or the validity of the study outcomes (e.g., high risk of neurologic events, worsening of clinical condition in the last 30 days) may be compromised by the subject's enrollment.
8. Pregnant or breast-feeding women or women who wish to become pregnant during the length of study participation.
9. Participating in another clinical trial during the follow-up period that could confound the treatment or outcomes of this investigation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pipeline™ Embolization Device; treatment with Pipeline™ Embolization Device	Device: Pipeline™ Embolization Device/ Pipeline™Flex Embolization Device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants With the Occurrence of Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 12-Months Post Procedure	The primary safety endpoint was defined as a stroke which results in focal neurological deficit for 24 hrs or more and increases the NIH Stroke Scale of the subject by ≥ 4 along with an imaging correlate. Missing data for subjects who failed to complete the 12- month post-procedure evaluation without any evidence of a major stroke in the territory supplied by the treated artery or neurological death were imputed in the analysis using multiple imputation. Multiple imputation provides a mechanism for deriving estimates for a population where not all of the patients have an endpoint determination.	Up to 12 Months Post Procedure
The Percentage of Participants With Complete Aneurysm Occlusion (Defined as Raymond Roy Grade 1) Without Significant Parent Artery Stenosis (≤ 50%) or Retreatment of the Target Aneurysm at 12-Months Post-Procedure	The definitions for the three components of the primary effectiveness endpoint were: 1) retreatment, defined as all retreatment procedures occurring between the index procedure and 1 Year post-procedure; 2) complete aneurysm occlusion based on Core Laboratory review of 1-year images and 3) significant parent artery stenosis, based on Core Laboratory review of 1-year images. The Raymond-Roy Grading scale is used for judging intracranial aneurysm (IA) endosaccular embolization success. Grade I is completion occlusion with no flow of contrast seen in the aneurysm sac, Grade II is partial occlusion with some flow or eddy flow in the aneurysm sac and Grade III is residual aneurysm or Incomplete occlusion with apparent flow in the aneurysm sac. Multiple imputation provides a mechanism for deriving estimates for a population where not all of the patients have an endpoint determination.	Up to 12 Months Post Procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With a Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 30-days Post Procedure Due to Procedural Complications	Major Stroke is defined as a stroke which results in focal neurological deficit for 24 hrs or more and increases the NIH Stroke Scale of the subject by ≥ 4 along with an imaging correlate. Neurological death is any subject death due to neurologic reasons.	Up to 30 days, Post Procedure
The Number of Participants Who Experienced Delayed Intracerebral Hemorrhage > 30 Days Post-Procedure	For the purpose of this protocol, delayed intracerebral hemorrhage was defined as hemorrhage within the fixed vault of the cranium (skull) occurring greater than 30 days post-procedure.	> 30 days, Post Procedure
The Number of Participants With Successfully Deployed Investigational Device	The secondary outcome measures provides the number of participants successfully implanted with the Investigational device during the study index procedure at the target site.	Index Procedure

Collaborators and Investigators

• Sponsor: Medtronic Neurovascular Clinical Affairs
• Investigators: Principal Investigator: Ricardo Hanel, M.D., Baptist Medical Center

Publications and helpful links

General Publications

• Hanel RA, Cortez GM, Lopes DK, Nelson PK, Siddiqui AH, Jabbour P, Mendes Pereira V, Istvan IS, Zaidat OO, Bettegowda C, Colby GP, Mokin M, Schirmer CM, Hellinger FR, Given C, Krings T, Taussky P, Toth G, Fraser JF, Chen M, Priest R, Kan P, Fiorella D, Frei D, Aagaard-Kienitz B, Diaz O, Malek AM, Cawley CM, Puri AS, Kallmes DF. Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification. J Neurointerv Surg. 2022 Mar 15:neurintsurg-2021-018501. doi: 10.1136/neurintsurg-2021-018501. Online ahead of print.
• Hanel RA, Kallmes DF, Lopes DK, Nelson PK, Siddiqui A, Jabbour P, Pereira VM, Szikora Istvan I, Zaidat OO, Bettegowda C, Colby GP, Mokin M, Schirmer C, Hellinger FR, Given Ii C, Krings T, Taussky P, Toth G, Fraser JF, Chen M, Priest R, Kan P, Fiorella D, Frei D, Aagaard-Kienitz B, Diaz O, Malek AM, Cawley CM, Puri AS. Prospective study on embolization of intracranial aneurysms with the pipeline device: the PREMIER study 1 year results. J Neurointerv Surg. 2020 Jan;12(1):62-66. doi: 10.1136/neurintsurg-2019-015091. Epub 2019 Jul 15.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2014
• Primary Completion (Actual): November 18, 2016
• Study Completion (Actual): December 13, 2018

Study Registration Dates

• First Submitted: July 8, 2014
• First Submitted That Met QC Criteria: July 9, 2014
• First Posted (Estimate): July 10, 2014

Study Record Updates

• Last Update Posted (Actual): December 27, 2019
• Last Update Submitted That Met QC Criteria: December 17, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Intracranial aneurysm; brain aneurysm
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Aneurysm; Intracranial Aneurysm
• Other Study ID Numbers: NV-PED-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No, there is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: Yes