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U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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ATLAS Study


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General
Study Status Study Pending
Application Number P180031 / PAS001
Date Current Protocol Accepted  
Study Name ATLAS Study
General Study Protocol Parameters
Study Design Prospective Cohort Study
Data Source New Data Collection
Comparison Group Objective Performance Criterion
Analysis Type Analytical
Study Population Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description Study Objective:

Data collected through the 12-month follow-up visit are intended to support Premarket Approval (PMA) application to the Food and Drug Administration (FDA). Long-term follow-up data collected through 3 years postoperative are intended to support postapproval study (PAS) requirements.



Study Design:

This study is designed as a prospective, multicenter, open-label, single-arm 2-cohort (anterior and posterior circulation) study. Eligible subjects presenting with a wide neck (neck greater than or equal to 4mm or a dome-to-neck ratio <2), intracranial, saccular aneurysm arising from a

parent vessel with a diameter of greater than or equal to 2mm and less than or equal to 4.5 mm will receive stent-assisted coiling

with the Neuroform Atlas™ Stent System and any approved bare metal embolic coils currently on the market.



Study Population Description Subjects invited to participate in this study will be those who have an aneurysm arising from a parent vessel with a diameter of 2.0 - 4.5 mm in either the distal anterior or posterior intracranial circulation that is accessible for endovascular treatment.

Anterior Circulation (AC) Cohort:

Up to 180 subjects with intracranial aneurysms in the anterior circulation (excluding the petrous ICA to superior hypophyseal ICA region) may be enrolled in order to provide 153 evaluable subjects at 12 months, with an estimated 15% attrition rate. These data will be used to support a safety and effectiveness analysis for an indication for use of the Neuroform Atlas™ Stent System in the anterior circulation.

Posterior Circulation (PC) Cohort:

Up to 180 subjects with intracranial aneurysms in the posterior circulation (including vertebral, basilar and posterior cerebral arteries) may be enrolled in order to provide 153 evaluable subjects at 12 months, with an estimated 15% attrition rate. These data will be analyzed separately from the AC Cohort data and will be used to support an indication for use of the Neuroform Atlas™ Stent System in the posterior circulation.



Sample Size Anterior Circulation Cohort:

A sample size of up to 180 subjects with intracranial aneurysms in the distal anterior circulation has been selected for this study in order to provide 153 evaluable subjects at 12 months, with an estimated 15% attrition rate. Assuming an effectiveness primary endpoint response rate of 62% (per the findings of a meta-analysis of Neuroform stent literature as performed by King et al[59]), the expected lower bound of the exact binomial two-sided 95% confidence interval around the success rate is greater than 50%. Assuming a safety primary endpoint rate of 8%, the expected upper bound of the exact binomial two sided 95% confidence interval around the success rate is less than 20%.

A sample size of 153 evaluable subjects provides 85% power to demonstrate the effectiveness endpoint, and a power of approximately 99% to successfully demonstrate the safety endpoint given the observed rates stated above. The combined probability of the two endpoints is (.85) x (.99) = .842.



Posterior Circulation Cohort:

Separate analyses of these cohort data will be performed to support an indication for use in the posterior circulation. A sample size of up to 180 subjects with intracranial aneurysms in the posterior circulation (including vertebral, basilar and posterior cerebral arteries) will also be enrolled in order to provide 153 evaluable subjects at 12 months, with an estimated 15% attrition rate. While the safety endpoint rate for posterior circulation subjects may be higher than that for the anterior circulation subjects, that rate is not expected to exceed 12%. Assuming a safety primary endpoint rate of 12%, the expected upper bound of the exact binomial two-sided 95% confidence interval around the success rate is less than 25%. A sample size of 153 evaluable subjects provides a power of approximately 99% to successfully demonstrate the safety endpoint given the observed rates stated above. Based on outcomes in the MAPS study, the effectiveness rate for posterior circulation subjects is expected to be very close to that of anterior circulation subjects. Therefore, the statement of power to demonstrate effectiveness for a sample size of 153 evaluable anterior circulation subjects also holds for a sample size of 153 evaluable posterior circulation subjects.

For the posterior circulation cohort, a Bayesian adaptive study design (“Goldilocks” approach) providing for interim analyses of accumulated data will be used to select the final sample-size. The first interim data analysis will occur once 100 posterior circulation subjects have been enrolled. Based on enrollment rates and the frequency of disease in the posterior circulation, at the time this interim analysis is performed it is estimated that primary endpoint data will be available for approximately 39 – 63 posterior circulation subjects. If, at an interim analysis, there is at least a 95% predictive probability of observing a true rate of complete occlusion that is higher than 50%, enrollment in the posterior circulation cohort will be stopped early for success. The maximum sample-size for the posterior circulation cohort will be no more than 180 subjects.



Data Collection The primary effectiveness endpoint of the study is:

Complete aneurysm occlusion (100% occlusion – Raymond Class 1) of the treated target lesion on 12 month angiography, in the absence of retreatment, or parent artery stenosis (> 50%) at the target location.



The primary safety endpoint of the study is: Any major ipsilateral stroke or neurological death within 12 months.

The secondary safety endpoint is: the percent of subjects experiencing one or more serious adverse events (SAEs) through 12 months post-index procedure within the following categories:

New or worsening major ipsilateral stroke as measured by the National Institute

of Health Stroke Scale (NIHSS)

Device-related SAEs

Subarachnoid hemorrhage (SAH)

Aneurysm rupture



The secondary effectiveness endpoints are: identified below will be assessed post-index procedure through 12 months per the schedule requirements:

Procedural technical success

Incidence of retreatment

Incidence of recanalization

Incidence of parent artery stenosis at the target aneurysm location (>50% stenosis)

Incidence of stent migration based on follow-up angiogram

Proportion of aneurysms with occlusion of Raymond Class 1, 2, or 3

Proportion of aneurysms with occlusion of Raymond Class 1 and 2 combined

Incidence of progressive occlusion at the target aneurysm location



The long-term follow-up endpoints:

The pre-specified safety endpoint is neurological death or major ipsilateral stroke at 12 months as adjudicated by the Clinical Events Committee (CEC). Long-term data on this pre-specified safety endpoint will continue to be collected. For the duration of the PAS study, all new or ongoing adverse events will be collected, reported, reviewed, and adjudicated per the CEC charter. Long-term safety events of interest will be grouped into the following combined categories for FDA reporting purposes:

Any ischemic or hemorrhagic adverse event of any severity or duration (including transient ischemic attacks [TIAs], subarachnoid hemorrhage [SAH],

and aneurysm rupture)

Device-related SAEs

For imaging performed per standard of care, the long-term effectiveness outcomes identified below will be assessed from 12 months through 3 years (+/- 6 months) postindex procedure per the long-term follow-up schedule requirements:

Retreatment

Parent artery stenosis at the target aneurysm location (>50% stenosis)

Composite effectiveness measure (complete aneurysm occlusion [Raymond Class 1] without significant parent artery stenosis at the target aneurysm location (>50% stenosis) or retreatment)

Recanalization

Stent migration based on follow-up angiogram

Aneurysm occlusion of Raymond Class 1, 2, or 3

Aneurysm occlusion of Raymond Class 1 and 2 combined

Progressive occlusion of the target aneurysm



Follow-up Visits and Length of Follow-up 3-year (+/- 6 months) follow-up.


ATLAS Study Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
six month report 11/14/2019 11/12/2019 On Time
one year report 05/15/2020 05/13/2020 On Time
18 month report 11/13/2020    
two year report 05/15/2021    
final report 10/31/2021    


Contact Us

Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov

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