LARGE Aneurysm Randomized Trial: Flow Diversion Versus Traditional Endovascular Coiling Therapy (LARGE)

February 9, 2018 updated by: Medical University of South Carolina
In this study, patients with large anterior circulation IAs with neck and fundus morphologies amenable to either traditional endovascular treatments using coils or reconstruction with the flow diversion will be randomly assigned to either treatment technique.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a prospective, randomized trial comparing the endovascular coiling (endovascular coiling) versus the flow diversion for large and giant aneurysm treatment. The endovascular coiling used in this study are FDA-approved and in common use at institutions in this country and across the world. The flow diversion devices are FDA-approved for anterior circulation aneurysms >10 mm and are in common use at institutions in this country and across the world. Patients will be enrolled who meet the inclusion criteria and consent to participate. Patients will be randomly assigned by a central web-based system in a 1:1 manner to treatment with either endovascular coiling or flow diversion. Data on each patient will be collected at the time of enrollment and treatment, and at subsequent follow-up visits.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
23

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • MUSC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  1. Age 21 to 75 years, inclusive

  2. Patient has a single target IA that: is located in the following regions of the internal carotid artery:

    1. Paraophthalmic (including paraclinoid, ophthalmic and hypophyseal segments)
    2. Cavernous
    3. Petrous
  3. has a parent vessel with diameter 2.5-5.0 mm
  4. Wide neck aneurysm ≥4 mm.
  5. Target IA has size (maximum fundus diameter) 10 mm
  6. The operator feels that the aneurysm can be appropriately treated with traditional endovascular techniques (endovascular coil embolization with or without adjunctive devices or parent artery deconstruction) using endovascular coiling or flow diversion devices.
  7. Modified Rankin Scale 0-3
  8. Signed and dated informed consent

4.2 Exclusion criteria

  1. More than one IA requiring treatment in the next 6 months
  2. Subarachnoid hemorrhage in the past 60 days
  3. Any intracranial hemorrhage in the last 42 days
  4. Major surgery (requiring general anesthesia) in the last 42 days
  5. Coils in place in the target IA
  6. Unstable neurologic deficit (i.e., any rapidly worsening clinical condition in the last 30 days (defined by a change in mRS of 2 or more))
  7. Known irreversible bleeding disorder
  8. Platelet count < 100 x 103 cells/mm3 or known platelet dysfunction
  9. Clinically documented evidence in medical history of adverse reaction or contraindication to medications used in treatment of the aneurysm (i.e. Plavix, heparin, aspirin)
  10. Prior stent placement at target site
  11. Documented history of dementia
  12. Contraindication to CT scan and MRI (ie. contrast allergy, or other condition that prohibits imaging from either CT or MRI)
  13. Known allergy to contrast used in angiography that cannot be medically controlled
  14. Known severe allergy to platinum or cobalt/chromium alloys
  15. Relative contraindication to angiography (e.g., serum creatinine > 2.5 mg/dL)
  16. Pregnancy, breast-feeding, or positive pregnancy test [either serum or urine] (Woman of child-bearing potential must have a negative pregnancy test prior to the study procedure.)
  17. Evidence of active infection (indicated by fever [at or over 99.9 °F] and/or open draining wound) at the time of randomization
  18. Other known conditions of the heart, blood, brain or intracranial vessels that carry a high risk of neurologic events (e.g., severe heart failure, atrial fibrillation, known carotid stenosis)
  19. Current use of cocaine or other illicit substance
  20. Any comorbid disease or condition expected to compromise survival or ability to complete Follow-up assessments through 180 days
  21. Extracranial stenosis greater than 50% in the carotid artery
  22. Intracranial stenosis greater than 50% in the treated vessel
  23. Based on investigator's judgment, patient does not have the necessary mental capacity to participate or is unwilling or unable to comply with protocol follow up appointment schedule.
  24. "Previously randomized into this trial or currently participating in another trial where the data is intended to be used to obtain marketing approval or to broaden an indication, without the approval of the study principal investigator, that may confound the results of this study.

A screen failure log of all cases referred or presented for possible inclusion, but who were not randomized, and the reason(s) for exclusion will be maintained.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Coiling
Procedure: Coiling
Endovascular coil placement
Active Comparator: Flow Diversion
Procedure: Flow Diversion
Endovascular flow diverter placement

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The primary aim of aneurysm treatment is to achieve occlusion of the IA without morbidity or mortality.
Time Frame: approaximately 180 days after aneurysm treatement procedure
Greater than 90% angiographic occlusion AND stable (or decreased) aneurysm size on cross sectional imaging (CT or MR) at 180 days post procedure. The primary objective is to show that flow diversion is non-inferior to endovascular coiling with respect to a combined efficacy and safety endpoint.
approaximately 180 days after aneurysm treatement procedure

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of device or procedure related adverse events at 180 days, 1 year and 3 years.
Time Frame: approximately 90 days, 180 days, 1 year, 2 year and 3 year
a count of the occurrences of device related Adverse Events will be recorded and compared between randomized groups at 90, 180, 1year, 2 year, and 3 year time points.
approximately 90 days, 180 days, 1 year, 2 year and 3 year
Subgroup analysis of clinical and angiographic outcomes in aneurysms 10-20 mm and > 2 cm.
Time Frame: approximately 3 years after aneurysm treatment procedure
A comparison will be made as a subgroup analysis of clinical and angiographic outcomes in aneurysms 10-20 mm and > 2 cm. will be measured based on efficacy (Greater than 90% angiographic occlusion AND stable (or decreased) aneurysm size on cross sectional imaging (CT or MR) at 180 days post procedure) and Safety (Free of any major neurologic event (defined as change in NIHSS from baseline > 4 points) downstream from target aneurysm, or death at 180 days post procedure) within this subgroup of study patients.
approximately 3 years after aneurysm treatment procedure
Downstream flow related ischemic stroke, parenchymal hemorrhage, subarachnoid hemorrhage, aneurysm rupture or re-treatment of index aneurysm rates at 180 days, one year and 3 years.
Time Frame: approaximately 180 days, 1 year, and 3 years after aneurysm treatement procedure
A count of occurrences of downstream flow related ischemic stroke, parenchymal hemorrhage, subarachnoid hemorrhage, aneurysm rupture or re-treatment of index aneurysm rates at 180 days, one year and 3 years. will be measured and compared at each time point: 180 days, 1 year, and 3 year between groups
approaximately 180 days, 1 year, and 3 years after aneurysm treatement procedure
Change in clinical functional outcome at 180 days, 1 year and 3 years post-endovascular treatment procedure, as measured by an increase in the modified Rankin Scale from baseline.
Time Frame: 180 days, 1 year and 3 years post-endovascular treatment procedure
A comparison between groups will be conducted of change in modified rankin scale. The comparison will be measured by an increase in the modified Rankin Scale from baseline, change in clinical functional outcome at 180 days, 1 year and 3 years post-endovascular treatment procedure, as measured by an increase in the modified Rankin Scale from baseline.
180 days, 1 year and 3 years post-endovascular treatment procedure
Incidence of worsening of baseline neurological signs/symptoms as measured by NIHSS/ophthalmologist exam related to target intracranial aneurysm (IA) at 180 days.
Time Frame: 180 days
A count and comparison of the incidence of worsening of baseline neurologic signs/symptoms as measured by national institutes of health stroke scale (NIHSS) or ophthalmological exam related to target IA at 180 days will be made between groups.
180 days
Number of inpatient hospital (and re-hospitalized) days (subgrouped >7 days) at 180 days, 1 year and 3 years.
Time Frame: 180 days, 1 year and 3 years.
A count and comparison of the number of inpatient hospital (and re-hospitalized) days (subgrouped >7 days) at 180 days, 1 year and 3 years will be performed between groups
180 days, 1 year and 3 years.
Packing density as measured by volumetric filling of the aneurysm if aneurysm is coiled.
Time Frame: after initial procedure, day 0
An analysis of packing density as measured by volumetric filling of the aneurysm if aneurysm is coiled will be performed. The analysis will show within group relationships and possible correlations among coiled patients and other variables.
after initial procedure, day 0
Device cost of therapy at treatment and any subsequent retreatment.
Time Frame: approximately 6 years after the initial procedure
Device cost of therapy at treatment and any subsequent retreatment will be counted and compared between groups in the study.
approximately 6 years after the initial procedure
Procedure time, as measured as the time from placement of the treating guide catheter for purposes of aneurysm treatment until guide catheter removal.
Time Frame: approximately 6 years after the initial procedure
Procedure time, as measured as the time from placement of the treating guide catheter for purposes of aneurysm treatment until guide catheter removal, will be collected, measured and compared between groups in the study.
approximately 6 years after the initial procedure
Subgroup analysis of clinical and angiographic outcomes in aneurysms intradural vs. extradural location
Time Frame: approximately 3 years after aneurysm treatment procedure
A comparison will be made as a subgroup analysis of clinical and angiographic outcomes in aneurysms of intradural vs. extradural location and will be measured based on efficacy (Greater than 90% angiographic occlusion AND stable (or decreased) aneurysm size on cross sectional imaging (CT or MR) at 180 days post procedure) and Safety (Free of any major neurologic event (defined as change in NIHSS from baseline > 4 points) downstream from target aneurysm, or death at 180 days post procedure) within this subgroup of study patients.
approximately 3 years after aneurysm treatment procedure
Subgroup analysis of clinical and angiographic outcomes in aneurysms reconstructive vs. deconstructive technique.
Time Frame: approximately 3 years after aneurysm treatment procedure
A comparison will be made as a subgroup analysis of clinical and angiographic outcomes in aneurysms treated with reconstructive vs. deconstructive technique and will be measured based on efficacy (Greater than 90% angiographic occlusion AND stable (or decreased) aneurysm size on cross sectional imaging (CT or MR) at 180 days post procedure) and Safety (Free of any major neurologic event (defined as change in NIHSS from baseline > 4 points) downstream from target aneurysm, or death at 180 days post procedure) within this subgroup of study patients.
approximately 3 years after aneurysm treatment procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of South Carolina

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Aquilla Turk, DO, Medical University of South Carolina

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 16, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 7, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 13, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO18426

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