Safety and Clinical Effectiveness of Pipeline™ Shield Devices for Intracranial Aneurysms (SCOPE-AUS)

The Safety and Clinical Effectiveness of Pipeline™ Flex Embolization Devices With Shield Technology™ in Patients With Intracranial Aneurysms: a Multicentre Retrospective Study of an Australian Cohort (SCOPE-AUS)

This observational, retrospective, single-arm, multi-centre cohort study will use real-world data (RWD) to develop real-world evidence (RWE) of the safety and clinical effectiveness of the Pipeline™ Flex Embolization Device with Shield Technology™ in Australian patients that have received a flow diversion device to treat an intracranial aneurysm (IA). The medical records from 500 procedures completed at Gold Coast University Hospital in Queensland (QLD), Prince of Wales Hospital in New South Wales (NSW), and Sir Charles Gardiner Hospital in Western Australia (WA), will be analysed.

The study will report the risk and likelihood of stroke (ischaemic and haemorrhagic), delayed neurological adverse events and incomplete aneurysm occlusion within sub-groups of the patient cohort and determine the predictive or confounding factors that influence clinical outcomes under pragmatic or 'real-world' conditions.

Study Overview

• Status: Unknown
• Conditions: Subarachnoid Hemorrhage; Cerebral Hemorrhage; Neurologic Disorder; Stroke, Acute; Cerebral Aneurysm; Intracranial Aneurysm; Cerebral Stroke
• Intervention / Treatment: Device: Pipeline™ Flex Embolization Device with Shield Technology™

Detailed Description

Methodology summary: Single-arm, longitudinal, retrospective, multi-centre cohort study. A collaboration of Australian Interventional Neuroradiologists will create a data bank of existing clinical and angiographic data extracted from medical records review. The data collection variables are pre-specified using grading scales and clinical assessment with the greatest reliability or significant to to accurately represent patient cohorts receiving treatment within all indications of use. The study will establish a minimum dataset to collect patient socio-demographics, aneurysm characteristics, device characteristics, and clinical outcomes for up to 500 procedures completed using Pipeline™ Flex Embolization Device with Shield Technology™. A framework for data ab The prevalence, severity and outcomes of neurological adverse events of interest and bleeding events will be reported . Independent physician assessments of complete aneurysm occlusion from completed computed tomography scans (CT), Magnetic Resonance Imaging (MRI) scans and Digital Subtraction Angiography (DSA) procedures will be determined according to the Raymond Roy Occlusion Classification (MRRC), O'Kelly Marotta scale (OKM) for aneurysm occlusion using flow diverting devices and the Consensus grading scale for endovascular aneurysm occlusion up to 12 months post procedure. Assessments of wall apposition and in-stent stenosis (ISS) will also be completed.

Quality Assurance plan includes - Framework data abstraction - manual of procedures, data dictionary, data abstraction manual, desired inter-rater reliability +0.80; intrarater reliability, intraclass correlation coefficient (ICC) 0.75 - 0.9;

Medical imaging review assessed by assess aneurysm occlusion by an independent interventional neuroradiologist or a local physician operator that did not complete the primary procedure. Physician level of agreement - interrater reliability to be reported;

Independent physician review of all post-op strokes (ischaemic, haemorrhagic) cases to determine aetiology/mechanism;

Study personnel training; Site visits; remote data monitoring, data audits.

Statistical analysis plan include descriptive statistics and regression models to report prevalence, mortality, time-to-event analyses and estimations of risk; Counts of medical records with insufficient data for analysis or where the patient is identified as 'lost follow-up', this will be reported.

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Maame Amma P Owusu RN, BSc, MNurSt, NVRN-BC; Phone Number: +61 7 5687 6447; Email: maame.owusu@health.qld.gov.au
• Study Contact Backup: Name: Henry (Hal) A Rice MBBS FRANZ; Phone Number: +61 7 5687 4430; Email: hal.rice@health.qld.gov.au

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Recruiting
      • Prince of Wales Hospital
      • Contact: Jason D Wenderoth MBBS(Hons 1) FRANZCR
      • Sub-Investigator: Andrew Cheung BSc MBBS(Hons 1) FRANZCR
      • Sub-Investigator: Nathan Manning BApSci, BSci(Hons), MBBS, FRANZCR CCINR
    • Sydney, New South Wales, Australia, 2170
      • Recruiting
      • Liverpool Hospital
      • Contact: Nathan Manning BApSci, BSci(Hons), MBBS, FRANZCR, CCINR FRANZCR
      • Sub-Investigator: Jason Wenderoth MBBS (Hons 1), FRANZCR
      • Sub-Investigator: Andrew Cheung BSc(Med), MBBS (Hons 1), FRANZCR
  • Queensland
    • Gold Coast, Queensland, Australia, 4215
      • Recruiting
      • Gold Coast University Hospital
      • Contact: Henry (Hal) A Rice MBBS FRANZCR
      • Contact: Maame Amma P Owusu RN BSc MNurst NVRN-BC; Phone Number: +61 7 5687 6447; Email: maame.owusu@health.qld.gov.au
      • Principal Investigator: Henry (Hal) A Rice MBBS FRANZCR
      • Principal Investigator: Laetitia E de Villiers MBCHB FRANZCR
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Not yet recruiting
      • Sir Charles Gairdner Hospital
      • Contact: Albert Chiu MBBS (Hons) FRANZCR
      • Sub-Investigator: William McAuliffe MBBS FRANZCR
      • Sub-Investigator: Timothy Phillips MBBS GDSA FRANZCR CCINR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The population is comprised of Australian patients aged ≥ 18 years that have received Pipeline™ Flex Embolization Devices with Shield Technology™ during a standard of care procedure to treat an IA. The patient selection period extends from 01 April 2015 to 30 June 2018.

Description

Inclusion Criteria:

• Patients ≥ 18 years of age
• Medical records from patients that have received a Pipeline™ Flex Embolization Device with Shield Technology™ inclusive of all indications such as an elective procedure, unscheduled procedure or emergency procedure for an unruptured or ruptured intracranial aneurysm(s) at each study site
• Medical records from patients that have received other neurovascular therapies such as coils, intracranial stents etc. with a Pipeline™ Flex Embolization Device with Shield Technology™ used as an adjunctive device during the index procedure

Exclusion Criteria:

• Medical records from patients that have not received a Pipeline™ Flex Embolization Device with Shield Technology™ to treat an intracranial aneurysm

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

patients with intracranial aneurysm(s); Standard of care elective, unscheduled or emergency procedures for the treatment of an unruptured or ruptured intracranial aneurysm(s) using a Pipeline™ Flex Embolization Device(s) with Shield Technology™

Device: Pipeline™ Flex Embolization Device with Shield Technology™; Neurointerventional procedures to treat intracranial (cerebral) aneurysms are minimally-invasive procedures performed by Interventional Neuroradiologists. The physician accesses the arterial system through a blood vessel in the groin followed by the insertion of a catheter. Pipeline™ Flex Embolization Device(s) with Shield Technology™,a flow diversion device, is implanted under high-magnification subtraction fluoroscopy, requiring the use of ancillary devices, such as micro-catheters and guidewires to complete the procedure under general anaesthetic. Procedural heparinisation and preloading with dual antiplatelet therapy (DAPT) using acetyl-salicylic acid and P2Y12 inhibitors such as clopidogrel or prasugrel are required.; Other Names: Neurointerventional procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of stroke (short-term)	Prevalence and severity of ischaemic and haemorrhagic stroke post procedure	30 days
Mortality due to stroke (short-term)	Number of deaths due to ischaemic and haemorrhagic post procedure	30 days
Morbidity due to neurological adverse events of interest (short-term)	Prevalence of neurological adverse events of interest post procedure	30 days
Prevalence of stroke (long-term)	Prevalence and severity of ischaemic and haemorrhagic stroke post procedure	12 months
Morbidity due to neurological adverse events of interest (long-term)	Prevalence of neurological adverse events of interest post procedure	12 months
Mortality due to stroke (long-term)	Number of deaths due to ischaemic and haemorrhagic post procedure	12 months
Mortality due to neurological adverse events of interest (long-term)	Deaths due to other neurological adverse events of interest	12 months
All cause mortality	Deaths due to any cause	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aneurysm occlusion - Wall apposition	Proportion of aneurysms with good wall apposition at post-operative time point	Day 0
Aneurysm occlusion - Consensus grading scale for endovascular occlusion (short-term)	Proportion of aneurysms with Grade 0 - 5 aneurysm occlusion; Grade 0 is complete aneurysm occlusion (better outcome; maximum score) Grade 5 is less than 25% aneurysm occlusion (worse outcome; minimum score)	6 months
Aneurysm occlusion - Consensus grading scale for endovascular occlusion (long-term)	Proportion of aneurysms with Grade 0 - 5 aneurysm occlusion; Grade 0 is complete aneurysm occlusion (better outcome; maximum score) Grade 5 is less than 25% aneurysm occlusion (worse outcome; minimum score)	12 months
Aneurysm occlusion - O'Kelly Marotta Scale (OKM; short-term)	Proportion of aneurysms with Grade D1 aneurysm occlusion on the O'Kelly Marotta Scale. Grade D1 indicates completed aneurysms occlusion as seen on the arterial phase of the cerebral angiogram due to 0% filling (better outcome; maximum score). Grade A1 represents total filling of the aneurysm (>95%) as seen on the arterial phase of the cerebral angiogram (worse outcome; minimum score).	6 months
Aneurysm occlusion - O'Kelly Marotta Scale (OKM; long-term)	Proportion of aneurysms with Grade D1 aneurysm occlusion on the O'Kelly Marotta Scale; Grade D1 indicates completed aneurysms occlusion as seen on the arterial phase of the cerebral angiogram due 0% filling (better outcome; maximum score). Grade A1 represents total filling of the aneurysm (>95%) as seen on the arterial phase of the cerebral angiogram (worse outcome; minimum score).	12 months
Aneurysm occlusion - Modified Raymond Roy Classification (MRRC; short-term)	Proportion of aneurysms with Class 1 occlusion. Class 1 indicates complete obliteration of the aneurysm neck, representing complete aneurysm occlusion (better outcome; maximum score). Class 3b indicates residual aneurysm with contrast along aneurysm wall, representing substantial blood flow into the aneurysm, poor occlusion of aneurysm neck (worst outcome; minimum score).	6 months
Aneurysm occlusion - Modified Raymond Ray Classification (MRRC; long-term)	Proportion of aneurysms with Class 1 occlusion. Class 1 indicates complete obliteration of the aneurysm neck, representing complete aneurysm occlusion (better outcome; maximum score). Class 3b indicates residual aneurysm with contrast along aneurysm wall, representing substantial blood flow into the aneurysm, poor occlusion of aneurysm neck (worst outcome; minimum score).	12 months
Aneurysm occlusion - In-stent stenosis (ISS; short-term)	Proportion of aneurysms with Grade 2-4 ISS; ISS is a focal area of parent cerebral vessel narrowing caused by thrombosis or intimal hypoplasia. Grade 0 indicates no ISS is present (better outcome, maximum score). Grade 4 indicates occlusion of the cerebral parent vessel (worst outcome, minimum score).	30 days
Aneurysm occlusion - In-stent stenosis (ISS; short-term)	Proportion of aneurysms with Grade 2-4 ISS; ISS is a focal area of parent cerebral vessel narrowing caused by thrombosis or intimal hypoplasia.Grade 0 indicates no ISS is present (better outcome, maximum score). Grade 4 indicates occlusion of the cerebral parent vessel (worst outcome, minimum score).	90 days
Aneurysm occlusion - In-stent stenosis (ISS; long-term)	Proportion of aneurysms with Grade 2-4 ISS; ISS is a focal area of parent cerebral vessel narrowing caused by thrombosis or intimal hypoplasia.Grade 0 indicates no ISS is present (better outcome, maximum score). Grade 4 indicates occlusion of the cerebral parent vessel (worst outcome, minimum score).	6 months
Aneurysm occlusion - In-stent stenosis (ISS; long-term)	Proportion of aneurysms with Grade 2-4 ISS; ISS is a focal area of parent cerebral vessel narrowing caused by thrombosis or intimal hypoplasia.Grade 0 indicates no ISS is present (better outcome, maximum score). Grade 4 indicates occlusion of the cerebral parent vessel (worst outcome, minimum score).	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional outcomes - Modified Rankin Scale, nil disability	Change in mRS from baseline mRS 0-1; mRS is a clinician-reported measure of global disability. Level 0 indicates no disability (better outcome, maximum score). Level 6 indicates death (worst outcome, minimum score).	90 days
Functional outcomes - Modified Rankin Scale, disability	Change in mRS from baseline mRS 3-6; mRS is a clinician-reported measure of global disability. Level 0 indicates no disability (better outcome, maximum score). Level 5 indicates severe disability, bedridden, incontinent and requiring nursing care and attention (poor outcome, low score). Level 6 indicates death (worst outcome, minimum score).	90 days
Functional outcomes - number of days spent in hospital	mean time in hospital, an intensive care unit, or rehabilitation facility	90 days
Functional outcomes - home time post stroke	Number of days spent at home after a post-operative stroke	90 days
Procedural time	Time from start to end of the procedure	Day 0
Dual anti platelet therapy (DAPT) - Assay values	% inhibition - DAPT assay values demonstrating impaired platelet activity	Day 0
Bleeding events - The Bleeding Academic Research Consortium	Proportion, severity and classification of bleeding events	12 months
Re-treatment procedures	Proportion of aneurysms requiring re-treatment procedures	12 months
Incomplete aneurysms occlusion	Proportion of aneurysms with incomplete occlusion	12 months

Collaborators and Investigators

• Sponsor: Gold Coast Hospital and Health Service
• Collaborators: Prince of Wales Hospital, Sydney; Sir Charles Gairdner Hospital; Liverpool Hospital, Sydney
• Investigators: Study Director: Henry (Hal) A Rice MBBS FRANZCR, Gold Coast University Hospital; Principal Investigator: Laetitia E de Villiers MBCHB FRANZCR, Gold Coast University Hospital; Principal Investigator: Jason D Wenderoth BSc MBBS (Hons 1) FRANZCR, Prince of Wales Hospital; Principal Investigator: Albert Chiu MBBS (Hons.) FRANZCR, Sir Charles Gardiner Hospital; Principal Investigator: Nathan Manning BApSci, BSci(Hons) MBBS FRANZCR CCINR, Liverpool Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2019
• Primary Completion (Anticipated): January 30, 2020
• Study Completion (Anticipated): September 30, 2020

Study Registration Dates

• First Submitted: October 6, 2018
• First Submitted That Met QC Criteria: January 23, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): December 10, 2019
• Last Update Submitted That Met QC Criteria: December 9, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Neurosurgery; Interventional Neuroradiology; Diagnostic neuroradiology; Neurovascular Devices; Flow Diversion Device
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Intracranial Arterial Diseases; Intracranial Hemorrhages; Stroke; Hemorrhage; Nervous System Diseases; Aneurysm; Subarachnoid Hemorrhage; Cerebral Hemorrhage; Intracranial Aneurysm
• Other Study ID Numbers: GCMR0002; ISR-2017-10909 (Other Grant/Funding Number: Medtronic External Research Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: This study will comply with the Australian Government Data Sharing Policy, the NHMRC Open Access Policy and the Clinical Trials Registration and Results Information Submission rule.

IPD Sharing Time Frame

To align with national recommendations for data sharing, the SCOPE-AUS metadata (description of the data) shall be published in a metadata record through Research Data Australia Registry, an entity of the Australian National Data Service. The goal is to ensure that data that is unique to the discipline of Interventional Neuroradiology is available for reuse in future research purposes.

The SCOPE-AUS metadata will be available at 12 months following primary publication until 48 months.

• IPD Sharing Access Criteria: Access shall be conditional; re-users must be genuine researchers whose proposed use of the data has been approved by an Ethics committee. Re-users are required to cite the SCOPE-AUS dataset in any scholarly outputs. This proposed strategy will uphold Australian privacy laws. The Sponsor/Coordinating Principal Investigator/SCOPE-AUS research team will ultimately retain oversight of all future uses of the data.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes