Intracranial AneurysmPhase 4LARGENCT01762137
LARGE Aneurysm Randomized Trial: Flow Diversion Versus Traditional Endovascular Coiling Therapy
A Phase 4 study testing Flow Diversion and Coiling in people with Intracranial Aneurysm, run by Medical University of South Carolina at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Intracranial Aneurysm
- What is being tested?
- Flow Diversion and Coiling
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Feb 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 21 to 75 years, inclusive
- Patient has a single target IA that: is located in the following regions of the internal carotid artery:
- Paraophthalmic (including paraclinoid, ophthalmic and hypophyseal segments)
- Cavernous
- Petrous
- has a parent vessel with diameter 2.5-5.0 mm
Show all 37Show fewer
- Wide neck aneurysm ≥4 mm.
- Target IA has size (maximum fundus diameter) 10 mm
- 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.
- Modified Rankin Scale 0-3
- Signed and dated informed consent
- 4.2 Exclusion criteria
- More than one IA requiring treatment in the next 6 months
- Subarachnoid hemorrhage in the past 60 days
- Any intracranial hemorrhage in the last 42 days
- Major surgery (requiring general anesthesia) in the last 42 days
- Coils in place in the target IA
- 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))
- Known irreversible bleeding disorder
- Platelet count < 100 x 103 cells/mm3 or known platelet dysfunction
- Clinically documented evidence in medical history of adverse reaction or contraindication to medications used in treatment of the aneurysm (i.e. Plavix, heparin, aspirin)
- Prior stent placement at target site
- Documented history of dementia
- Contraindication to CT scan and MRI (ie. contrast allergy, or other condition that prohibits imaging from either CT or MRI)
- Known allergy to contrast used in angiography that cannot be medically controlled
- Known severe allergy to platinum or cobalt/chromium alloys
- Relative contraindication to angiography (e.g., serum creatinine > 2.5 mg/dL)
- 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.)
- Evidence of active infection (indicated by fever [at or over 99.9 °F] and/or open draining wound) at the time of randomization
- 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)
- Current use of cocaine or other illicit substance
- Any comorbid disease or condition expected to compromise survival or ability to complete Follow-up assessments through 180 days
- Extracranial stenosis greater than 50% in the carotid artery
- Intracranial stenosis greater than 50% in the treated vessel
- 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.
- "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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Intracranial Aneurysm
- Being tested
- Flow Diversion, Coiling
- Keywords
- Aneurysm, Coiling, Flow Diversion
- Medical subject headings
- Intracranial Aneurysm, Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flow DiversionProcedure or surgery
Endovascular flow diverter placement
CoilingProcedure or surgery
Endovascular coil placement
| Study group | Role | What they receive |
|---|---|---|
| Coiling | Active comparator | Coiling Receives: Procedure: Coiling |
| Flow Diversion | Active comparator | Flow Diversion Receives: Procedure: Flow Diversion |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary aim of aneurysm treatment is to achieve occlusion of the IA without morbidity or mortality.
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.
Measured: approaximately 180 days after aneurysm treatement procedure
Secondary outcomes (11)
Incidence of device or procedure related adverse events at 180 days, 1 year and 3 years.
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.
Measured: 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.
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.
Measured: 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.
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
Measured: 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.
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.
Measured: 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.
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.
Measured: 180 days
Number of inpatient hospital (and re-hospitalized) days (subgrouped >7 days) at 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
Measured: 180 days, 1 year and 3 years.
Packing density as measured by volumetric filling of the aneurysm if aneurysm is coiled.
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.
Measured: after initial procedure, day 0
Device cost of therapy at treatment and any subsequent retreatment.
Device cost of therapy at treatment and any subsequent retreatment will be counted and compared between groups in the study.
Measured: 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.
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.
Measured: approximately 6 years after the initial procedure
Subgroup analysis of clinical and angiographic outcomes in aneurysms intradural vs. extradural location
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.
Measured: approximately 3 years after aneurysm treatment procedure
Subgroup analysis of clinical and angiographic outcomes in aneurysms reconstructive vs. deconstructive technique.
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.
Measured: approximately 3 years after aneurysm treatment procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionFeb 2017
- Study completionFeb 2017
Why it stopped: Rarity of disease and current practice in the field made enrollment challenging.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intracranial AneurysmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Aquilla Turk, DO, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01762137
- Sponsor's protocol ID
- PRO18426
- Acronym
- LARGE
- Status last verified
- Feb 2018
- First submitted
- 16 Nov 2012
- Last updated
- 13 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LARGE Aneurysm Randomized Trial: Flow Diversion Versus Traditional Endovascular Coiling Therapy
- ClinicalTrials.gov ID
- NCT01762137
- Acronym / sponsor ID
- LARGE / PRO18426
- Conditions
- Intracranial Aneurysm
- Keywords
- Aneurysm, Coiling, Flow Diversion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Rarity of disease and current practice in the field made enrollment challenging.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Feb 2017 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 7 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Coiling | Active comparator | Procedure: CoilingCoiling |
| Flow Diversion | Active comparator | Procedure: Flow DiversionFlow Diversion |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- Age 21 to 75 years, inclusive
- Patient has a single target IA that: is located in the following regions of the internal carotid artery:
- has a parent vessel with diameter 2.5-5.0 mm
- Wide neck aneurysm ≥4 mm.
- Target IA has size (maximum fundus diameter) 10 mm
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Flow DiversionEndovascular flow diverter placement | Procedure or surgery | Flow Diversion |
| CoilingEndovascular coil placement | Procedure or surgery | Coiling |
Primary outcome
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.
11 secondary outcomes
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
Subgroup analysis of clinical and angiographic outcomes in aneurysms 10-20 mm and > 2 cm.
Time frame: 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
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
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
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.
Packing density as measured by volumetric filling of the aneurysm if aneurysm is coiled.
Time frame: after initial procedure, day 0
Device cost of therapy at treatment and any subsequent retreatment.
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.
Time frame: 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
Subgroup analysis of clinical and angiographic outcomes in aneurysms reconstructive vs. deconstructive technique.
Time frame: approximately 3 years after aneurysm treatment procedure
Results and safety
The study was stopped early (reason given: Rarity of disease and current practice in the field made enrollment challenging.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aquilla Turk, DO principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Flow Diversion and Coiling in people with Intracranial Aneurysm, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Rarity of disease and current practice in the field made enrollment challenging.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2018.