Intracranial Aneurysm
Conditions
Keywords
Intracranial aneurysm, brain aneurysm
Brief summary
The purpose of this study is to assess the safety and effectiveness of the Pipeline™ device in the treatment of unruptured, wide-neck intracranial aneurysms.
Interventions
DEVICEPipeline™ Embolization Device/ Pipeline™Flex Embolization Device
Sponsors
Medtronic Neurovascular Clinical Affairs
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has provided written informed consent using the IRB/EC-approved consent form and agrees to comply with protocol requirements. 2. Age 22-80 years. 3. Subject has a target intracranial aneurysm (IA) located in the: 1. Internal carotid artery (up to the carotid terminus) OR 2. Vertebral artery segment up to and including the posterior inferior cerebellar artery 4. Subject has a target IA that is ≤ 12 mm. 5. Subject has a target IA that has a parent vessel with diameter 1.5-5.0 mm distal/proximal to the target IA. 6. Subject has a target IA with an aneurysm neck ≥ 4mm or a dome to neck ratio ≤ 1.5. 7. Subject has a pre-procedure PRU value between 60-200.
Exclusion criteria
1. Subject has received an intracranial implant (e.g. coils) in the area of the target IA within the past 12 weeks. 2. Subarachnoid hemorrhage in the past 30 days. 3. Subject with anatomy not appropriate for endovascular treatment due to severe intracranial vessel tortuosity or stenosis determined from baseline or pre-procedure imaging, or a history of intracranial vasospasm not responsive to medical therapy. 4. Major surgery in the last 30 days. 5. History of irreversible bleeding disorder and/or subject presents with signs of active bleeding. 6. Any known contraindication to treatment with the Pipeline™ device, including: 1. Stent is in place in the parent artery at the target IA location 2. Contraindication to dual antiplatelet therapy 3. Relative contraindication to angiography (e.g., serum creatinine \>2.5 mg/dL, allergy to contrast that cannot be medically controlled). 4. Known severe allergy to platinum or cobalt/chromium alloys. 5. Evidence of active infection at the time of treatment (e.g., fever with temperature \>38°C and/or WBC \>1.5 109/L). 7. The Investigator determines that the health of the subject or the validity of the study outcomes (e.g., high risk of neurologic events, worsening of clinical condition in the last 30 days) may be compromised by the subject's enrollment. 8. Pregnant or breast-feeding women or women who wish to become pregnant during the length of study participation. 9. Participating in another clinical trial during the follow-up period that could confound the treatment or outcomes of this investigation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With the Occurrence of Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 12-Months Post Procedure | Up to 12 Months Post Procedure | The primary safety endpoint was defined as a stroke which results in focal neurological deficit for 24 hrs or more and increases the NIH Stroke Scale of the subject by ≥ 4 along with an imaging correlate. Missing data for subjects who failed to complete the 12- month post-procedure evaluation without any evidence of a major stroke in the territory supplied by the treated artery or neurological death were imputed in the analysis using multiple imputation. Multiple imputation provides a mechanism for deriving estimates for a population where not all of the patients have an endpoint determination. |
| The Percentage of Participants With Complete Aneurysm Occlusion (Defined as Raymond Roy Grade 1) Without Significant Parent Artery Stenosis (≤ 50%) or Retreatment of the Target Aneurysm at 12-Months Post-Procedure | Up to 12 Months Post Procedure | The definitions for the three components of the primary effectiveness endpoint were: 1) retreatment, defined as all retreatment procedures occurring between the index procedure and 1 Year post-procedure; 2) complete aneurysm occlusion based on Core Laboratory review of 1-year images and 3) significant parent artery stenosis, based on Core Laboratory review of 1-year images. The Raymond-Roy Grading scale is used for judging intracranial aneurysm (IA) endosaccular embolization success. Grade I is completion occlusion with no flow of contrast seen in the aneurysm sac, Grade II is partial occlusion with some flow or eddy flow in the aneurysm sac and Grade III is residual aneurysm or Incomplete occlusion with apparent flow in the aneurysm sac. Multiple imputation provides a mechanism for deriving estimates for a population where not all of the patients have an endpoint determination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With a Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 30-days Post Procedure Due to Procedural Complications | Up to 30 days, Post Procedure | Major Stroke is defined as a stroke which results in focal neurological deficit for 24 hrs or more and increases the NIH Stroke Scale of the subject by ≥ 4 along with an imaging correlate. Neurological death is any subject death due to neurologic reasons. |
| The Number of Participants Who Experienced Delayed Intracerebral Hemorrhage > 30 Days Post-Procedure | > 30 days, Post Procedure | For the purpose of this protocol, delayed intracerebral hemorrhage was defined as hemorrhage within the fixed vault of the cranium (skull) occurring greater than 30 days post-procedure. |
| The Number of Participants With Successfully Deployed Investigational Device | Index Procedure | The secondary outcome measures provides the number of participants successfully implanted with the Investigational device during the study index procedure at the target site. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PREMIER The investigational device was implanted in the internal carotid artery (up to the terminus) or the vertebral artery segment up to and including the posterior inferior cerebellar artery to treat unruptured, wide-necked, aneurysms measuring ≤ 12 mm. | 141 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 1- Year Post Index Procedure Visit | Death | 1 |
| 1- Year Post Index Procedure Visit | Missed | 1 |
| 30-Day Post Index Procedure Visit | Death | 1 |
| Enrollment | Did Not Meet Inclusion Criteria | 46 |
| Enrollment | Enrollment Cap Reached | 5 |
| Enrollment | Insurance Denial | 2 |
| Enrollment | Investigator Withdrew Consent | 1 |
| Enrollment | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | PREMIER |
|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 11.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 114 Participants |
| Region of Enrollment Canada | 6 participants |
| Region of Enrollment United States | 135 participants |
| Sex: Female, Male Female | 124 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 141 | 1 / 141 | 2 / 141 |
| other Total, other adverse events | 107 / 141 | 112 / 141 | 112 / 141 |
| serious Total, serious adverse events | 39 / 141 | 49 / 141 | 60 / 141 |
Outcome results
Primary
The Percentage of Participants With Complete Aneurysm Occlusion (Defined as Raymond Roy Grade 1) Without Significant Parent Artery Stenosis (≤ 50%) or Retreatment of the Target Aneurysm at 12-Months Post-Procedure
The definitions for the three components of the primary effectiveness endpoint were: 1) retreatment, defined as all retreatment procedures occurring between the index procedure and 1 Year post-procedure; 2) complete aneurysm occlusion based on Core Laboratory review of 1-year images and 3) significant parent artery stenosis, based on Core Laboratory review of 1-year images. The Raymond-Roy Grading scale is used for judging intracranial aneurysm (IA) endosaccular embolization success. Grade I is completion occlusion with no flow of contrast seen in the aneurysm sac, Grade II is partial occlusion with some flow or eddy flow in the aneurysm sac and Grade III is residual aneurysm or Incomplete occlusion with apparent flow in the aneurysm sac. Multiple imputation provides a mechanism for deriving estimates for a population where not all of the patients have an endpoint determination.
Time frame: Up to 12 Months Post Procedure
Population: Participants Treated with Investigational Device that Completed the 12 Month Visit Imaging
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PREMIER | The Percentage of Participants With Complete Aneurysm Occlusion (Defined as Raymond Roy Grade 1) Without Significant Parent Artery Stenosis (≤ 50%) or Retreatment of the Target Aneurysm at 12-Months Post-Procedure | 76.71 Percentage of Participants |
Primary
The Percentage of Participants With the Occurrence of Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 12-Months Post Procedure
The primary safety endpoint was defined as a stroke which results in focal neurological deficit for 24 hrs or more and increases the NIH Stroke Scale of the subject by ≥ 4 along with an imaging correlate. Missing data for subjects who failed to complete the 12- month post-procedure evaluation without any evidence of a major stroke in the territory supplied by the treated artery or neurological death were imputed in the analysis using multiple imputation. Multiple imputation provides a mechanism for deriving estimates for a population where not all of the patients have an endpoint determination.
Time frame: Up to 12 Months Post Procedure
Population: Participants enrolled and implanted with the Investigational Device (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PREMIER | The Percentage of Participants With the Occurrence of Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 12-Months Post Procedure | 2.17 percentage of participants |
Secondary
The Number of Participants Who Experienced Delayed Intracerebral Hemorrhage > 30 Days Post-Procedure
For the purpose of this protocol, delayed intracerebral hemorrhage was defined as hemorrhage within the fixed vault of the cranium (skull) occurring greater than 30 days post-procedure.
Time frame: > 30 days, Post Procedure
Population: ParticipantsTreated with the Investigational Device that Completed the 30 Day Visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PREMIER | The Number of Participants Who Experienced Delayed Intracerebral Hemorrhage > 30 Days Post-Procedure | 1 Participants |
Secondary
The Number of Participants With a Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 30-days Post Procedure Due to Procedural Complications
Major Stroke is defined as a stroke which results in focal neurological deficit for 24 hrs or more and increases the NIH Stroke Scale of the subject by ≥ 4 along with an imaging correlate. Neurological death is any subject death due to neurologic reasons.
Time frame: Up to 30 days, Post Procedure
Population: Participants Treated with the Investigational Device that Completed the 30 Day Visit
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PREMIER | The Number of Participants With a Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 30-days Post Procedure Due to Procedural Complications | 0 Participants |
Secondary
The Number of Participants With Successfully Deployed Investigational Device
The secondary outcome measures provides the number of participants successfully implanted with the Investigational device during the study index procedure at the target site.
Time frame: Index Procedure
Population: Participants Enrolled who Underwent the Index Procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PREMIER | The Number of Participants With Successfully Deployed Investigational Device | 140 Participants |