Intracranial Aneurysm
Conditions
Keywords
neurovascular embolization, therapeutic embolization
Brief summary
To determine the safety and effectiveness of Pipeline Embolization Device for the treatment of uncoilable or failed wide-necked intracranial aneurysms (IA).
Detailed description
Patients with large or giant aneurysms of the internal carotid artery treated with PED. Angiographic follow-up occurs at 3 and 5 years.
Interventions
1 or more PEDs placed in the parent artery of the affected aneurysm via endovascular approach
Sponsors
Medtronic Neurovascular Clinical Affairs
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 21 to 75 years, inclusive * Patient has a single target IA in the anterior or posterior circulation that: a) Is located in the following regions of the internal carotid artery: i. Paraophthalmic (including paraclinoid, ophthalmic and hypophyseal segments) ii. Cavernous iii. Petrous b) Has a neck \>4 mm or no discernible neck AND a size (maximum fundus diameter) \>10 mm c) Has a parent vessel with diameter 2.5 - 5.0 mm distal/proximal to the target IA * Subject has provided written informed consent using the Institutional Review Board (IRB)-approved consent form * Subject has the necessary mental capacity to participate and is willing and able to comply with protocol requirements
Exclusion criteria
* More than one IA requires treatment in the next 6 months * Subarachnoid hemorrhage from target IA in the past 60 days * Unstable neurologic deficit (i.e., any worsening of clinical condition in the last 30 days) * Irreversible bleeding disorder * Platelet count \< 100 x 103 cells/mm3 or known platelet dysfunction * Inability to tolerate, documented evidence of adverse reaction or contraindication to study medications * Stent in place at the target IA * Contraindication to CT scan or MRI * 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) * Woman of child-bearing potential who cannot provide a negative pregnancy test * Evidence of active infection at the time of treatment * Other 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) * Any comorbid disease or condition expected to compromise survival or ability to complete follow-up assessments to 180 days * Extracranial stenosis greater than 50% in the carotid artery for anterior circulation aneurysms * Intracranial stenosis greater than 50% in the treated vessel
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Occurrence of Major Ipsilateral Stroke or Neurologic Death and Occurrence of Ipsilateral Stroke or Neurologic Death. | 180-days and 5-years | The number of participants with occurrence of major ipsilateral stroke or neurologic death after PED placement at 180-days and the occurrence of ipsilateral stroke or neurologic death after Pipeline Embolization Devices (PED) placement at 5-years. |
| Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) Without Major Parent Artery Stenosis. | 180 days | The count of Intracranial Aneurysms (IA) evaluated as completely occluded (defined as Raymond Grade 1) without major parent artery stenosis at 180 days. The Raymond-Roy Grade scale measures the amount of visual contrast flow throughout the aneurysm anatomy. The Raymond-Roy aneurysm occlusion scale is follows: Complete = complete occlusion, no flow of contrast seen in the sac Residual Neck = partial occlusion, some flow, or eddying flow, in the sac Residual Aneurysm = incomplete occlusion, apparent flow into the sac |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) at 5 Years | 5 years | The count of Intracranial Aneurysms (IA) evaluated as completely occluded (100%) (defined as Raymond-Roy grade 1) at 5-year follow-up. The Raymond-Roy Grade scale measures the amount of visual contrast flow throughout the aneurysm anatomy. The Raymond-Roy aneurysm occlusion scale is follows: Complete = complete occlusion, no flow of contrast seen in the sac Residual Neck = partial occlusion, some flow, or eddying flow, in the sac Residual Aneurysm = incomplete occlusion, apparent flow into the sac |
| Stenosis of the Parent Artery in PED at 3 Years | 3-years | Parent artery stenosis (narrowing of the artery from which the aneurysm arises) at 3-year follow-up |
| Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) at 1 Year | 1 Year | The count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) (defined as Raymond-Roy grade 1) 1 year follow-up visit. The Raymond-Roy Grade scale measures the amount of visual contrast flow throughout the aneurysm anatomy. The Raymond-Roy aneurysm occlusion scale is follows: Complete = complete occlusion, no flow of contrast seen in the sac Residual Neck = partial occlusion, some flow, or eddying flow, in the sac Residual Aneurysm = incomplete occlusion, apparent flow into the sac |
| Number of Participants With Device-Related Adverse Events at 3 Years | 3 years | Number of participants with incidence of device-related adverse events at 3 year follow-up |
| Number of Participants With Device-related Adverse Events at 5 Years | 5 years | Subjects Observed with Device Related Adverse Events 5 years after Pipeline Placement |
| Stenosis of the Parent Artery in PED at 5 Years | 5-years | Parent artery stenosis at 5-year follow-up |
| Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) at 3 Year Follow-up | 3 years | The count of Intracranial Aneurysms (IA) evaluated as completely occluded (100%) (defined as Raymond-Roy grade 1) at 3 year follow-up. The Raymond-Roy Grade scale measures the amount of visual contrast flow throughout the aneurysm anatomy. The Raymond-Roy aneurysm occlusion scale is follows: Complete = complete occlusion, no flow of contrast seen in the sac Residual Neck = partial occlusion, some flow, or eddying flow, in the sac Residual Aneurysm = incomplete occlusion, apparent flow into the sac |
Countries
Hungary, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pipeline Placement of Pipeline Embolization Device in the parent artery at the aneurysm location
Pipeline Embolization Device (PED): 1 or more PEDs placed in the parent artery of the affected aneurysm via endovascular approach | 108 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | PED Treatment not attempted | 1 |
Baseline characteristics
| Characteristic | Pipeline |
|---|---|
| Age, Continuous | 57 Years STANDARD_DEVIATION 11.3 |
| Region of Enrollment Hungary | 14 Participants |
| Region of Enrollment Turkey | 18 Participants |
| Region of Enrollment United States | 76 Participants |
| Sex: Female, Male Female | 96 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 74 / 107 |
| serious Total, serious adverse events | 55 / 107 |
Outcome results
Primary
Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) Without Major Parent Artery Stenosis.
The count of Intracranial Aneurysms (IA) evaluated as completely occluded (defined as Raymond Grade 1) without major parent artery stenosis at 180 days. The Raymond-Roy Grade scale measures the amount of visual contrast flow throughout the aneurysm anatomy. The Raymond-Roy aneurysm occlusion scale is follows: Complete = complete occlusion, no flow of contrast seen in the sac Residual Neck = partial occlusion, some flow, or eddying flow, in the sac Residual Aneurysm = incomplete occlusion, apparent flow into the sac
Time frame: 180 days
Population: A total of 104 participants and 106 intracranial aneurysms treated with the Pipeline Embolization Device were included in the primary effectiveness endpoint analysis.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Pipeline | Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) Without Major Parent Artery Stenosis. | 78 Fully Occluded Intracranial Aneurysms |
p-value: <0.001Bayesian
Primary
Number of Participants With the Occurrence of Major Ipsilateral Stroke or Neurologic Death and Occurrence of Ipsilateral Stroke or Neurologic Death.
The number of participants with occurrence of major ipsilateral stroke or neurologic death after PED placement at 180-days and the occurrence of ipsilateral stroke or neurologic death after Pipeline Embolization Devices (PED) placement at 5-years.
Time frame: 180-days and 5-years
Population: Patients treated with one or more Pipeline Embolization Devices.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pipeline | Number of Participants With the Occurrence of Major Ipsilateral Stroke or Neurologic Death and Occurrence of Ipsilateral Stroke or Neurologic Death. | 180-Days | 6 Participants |
| Pipeline | Number of Participants With the Occurrence of Major Ipsilateral Stroke or Neurologic Death and Occurrence of Ipsilateral Stroke or Neurologic Death. | 5-Years | 10 Participants |
p-value: <0.001Bayesian
Secondary
Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) at 1 Year
The count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) (defined as Raymond-Roy grade 1) 1 year follow-up visit. The Raymond-Roy Grade scale measures the amount of visual contrast flow throughout the aneurysm anatomy. The Raymond-Roy aneurysm occlusion scale is follows: Complete = complete occlusion, no flow of contrast seen in the sac Residual Neck = partial occlusion, some flow, or eddying flow, in the sac Residual Aneurysm = incomplete occlusion, apparent flow into the sac
Time frame: 1 Year
Population: Pipeline treated subjects with observable data at 1 year
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Pipeline | Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) at 1 Year | 79 Target Intracranial Aneurysms |
Secondary
Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) at 3 Year Follow-up
The count of Intracranial Aneurysms (IA) evaluated as completely occluded (100%) (defined as Raymond-Roy grade 1) at 3 year follow-up. The Raymond-Roy Grade scale measures the amount of visual contrast flow throughout the aneurysm anatomy. The Raymond-Roy aneurysm occlusion scale is follows: Complete = complete occlusion, no flow of contrast seen in the sac Residual Neck = partial occlusion, some flow, or eddying flow, in the sac Residual Aneurysm = incomplete occlusion, apparent flow into the sac
Time frame: 3 years
Population: Pipeline treated Subjects with observable data at 3 years
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Pipeline | Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) at 3 Year Follow-up | 71 Target Intracranial Aneurysms |
Secondary
Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) at 5 Years
The count of Intracranial Aneurysms (IA) evaluated as completely occluded (100%) (defined as Raymond-Roy grade 1) at 5-year follow-up. The Raymond-Roy Grade scale measures the amount of visual contrast flow throughout the aneurysm anatomy. The Raymond-Roy aneurysm occlusion scale is follows: Complete = complete occlusion, no flow of contrast seen in the sac Residual Neck = partial occlusion, some flow, or eddying flow, in the sac Residual Aneurysm = incomplete occlusion, apparent flow into the sac
Time frame: 5 years
Population: Pipeline treated subjects with observable data at 5 years
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Pipeline | Count of Intracranial Aneurysms (IA) Evaluated as Completely Occluded (100%) at 5 Years | 59 Target Intracranial Aneurysms |
Secondary
Number of Participants With Device-Related Adverse Events at 3 Years
Number of participants with incidence of device-related adverse events at 3 year follow-up
Time frame: 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pipeline | Number of Participants With Device-Related Adverse Events at 3 Years | 4 Participants |
Secondary
Number of Participants With Device-related Adverse Events at 5 Years
Subjects Observed with Device Related Adverse Events 5 years after Pipeline Placement
Time frame: 5 years
Population: Subjects Observed with Device Related Adverse Events 5 years after Pipeline Placement
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pipeline | Number of Participants With Device-related Adverse Events at 5 Years | 2 Participants |
Secondary
Stenosis of the Parent Artery in PED at 3 Years
Parent artery stenosis (narrowing of the artery from which the aneurysm arises) at 3-year follow-up
Time frame: 3-years
Population: Subjects that completed imaging at the 3-year follow-up were included in the parent artery stenosis analysis.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Pipeline | Stenosis of the Parent Artery in PED at 3 Years | Stenosis 0 - 25% | 67 Parent Artery Assessments |
| Pipeline | Stenosis of the Parent Artery in PED at 3 Years | Stenosis > 25 - 50% | 8 Parent Artery Assessments |
| Pipeline | Stenosis of the Parent Artery in PED at 3 Years | Stenosis >50% - 75% | 0 Parent Artery Assessments |
| Pipeline | Stenosis of the Parent Artery in PED at 3 Years | Stenosis >75% | 3 Parent Artery Assessments |
| Pipeline | Stenosis of the Parent Artery in PED at 3 Years | Indeterminate | 7 Parent Artery Assessments |
Secondary
Stenosis of the Parent Artery in PED at 5 Years
Parent artery stenosis at 5-year follow-up
Time frame: 5-years
Population: Subjects that completed imaging at the 5-year follow-up were included in the parent artery stenosis analysis.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Pipeline | Stenosis of the Parent Artery in PED at 5 Years | Stenosis 0 - 25% | 50 Parent Artery Assessments |
| Pipeline | Stenosis of the Parent Artery in PED at 5 Years | Stenosis >25 - 50% | 3 Parent Artery Assessments |
| Pipeline | Stenosis of the Parent Artery in PED at 5 Years | Stenosis >50 - 75% | 1 Parent Artery Assessments |
| Pipeline | Stenosis of the Parent Artery in PED at 5 Years | Stenosis >75% | 2 Parent Artery Assessments |
| Pipeline | Stenosis of the Parent Artery in PED at 5 Years | Indeterminate | 8 Parent Artery Assessments |