Cerebral Aneurysm
Conditions
Keywords
treatment trial, cerebral aneurysm, randomized, coils, endovascular, HEAT, bare platinum, Hydrogel, Hydrocoil
Brief summary
This research study is being done to test the effectiveness of a new generation FDA approved device for treating aneurysms compared to the current standard device for endovascular aneurysm treatment which is bare platinum coils. Endovascular procedures are a form of minimally invasive surgery, which is performed on blood vessels. The technique involves the introduction of a catheter which is a long, thin, flexible, hollow plastic tube through the skin into a large blood vessel. Typically the chosen blood vessel is the femoral artery found near the groin. The catheter is then maneuvered through the body to the location of the aneurysm in the brain using image guidance. Coils are delivered into the aneurysm through the catheters. Once the coils are delivered in the aneurysm, they are detached from the catheter. This is repeated until enough coils fill the aneurysm, blocking the blood flow to the aneurysm. The body responds by forming blood clots around the coil(s), which helps block the flow of blood into the aneurysm and keeps the vessel from rupturing or leaking. This study will compare the study device to the standard bare platinum coil to see which is better at preventing future rupturing or leaking. The study device is called the HydroCoil Embolization System and this study is a post-market clinical trial. About 600 subjects from multiple institutions will take part in this study.
Detailed description
Your part in this study will last up to 24 months and will involve 6 visits (1 baseline visit before your surgery, the surgical procedure and 4 follow-up visits). These visits will occur at the same time as the visits you would receive as standard of care after your surgery. If you are in this study, you will be placed in one of two study groups by chance using a process similar to the flip of a coin. This process is called randomization. Neither you nor the study staff will select the group you will be in. One group, the control group, will have their aneurysm treated by the bare platinum coils during their endovascular procedure. The other group, the study group will receive coils from the HydroCoil Embolization System. Both groups will receive the same standard of care and follow-up, but during the surgery different types of coils will be used.
Interventions
DEVICEHydroCoil Embolic System
HydroCoil Embolic System
DEVICEControl (bare platinum coils)
bare platinum coils
Sponsors
MicroVention, Inc.
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Candidates for this study must meet the following criteria to be enrolled in the study: 1. Patient is between 18 and 75 years of age (inclusive). 2. Patient has a documented untreated intracranial saccular aneurysm 3-14 mm diameter angiographic lumen, ruptured or unruptured, suitable for embolization with coils. 3. Patients presenting with a HUNT and HESS Grade 0-3 or improving to such a grade before treatment 4. Any type of bare platinum coils and HydroCoil ® Coils are treatment options (all shapes allowed). 5. Patient or next of kin or person with appropriate power of attorney has provided written informed consent. 6. Patient is willing and available for study follow-up visits 7. Patient has not been previously entered into this Study
Exclusion criteria
Candidates will be ineligible for enrollment in the study if any of the following conditions apply: 1. Inability to obtain informed consent 2. Patient is \< 18 or \> 75 years old 3. Target aneurysm is not saccular in nature (mycotic, fusiform, dissecting). 4. Target aneurysm is \> 14 mm maximum luminal dimension, \< 3 mm maximum luminal dimension 5. Target aneurysm has been previously clipped or coiled 6. Target aneurysm is in the physician's estimate unlikely to be successfully treated by endovascular techniques. 7. Patient has known hypersensitivity to platinum, nickel, stainless steel or structurally related compounds found in HydroCoil®, HydroSoft®, HydroFrame® Coils and/or bare platinum coils. 8. Baseline Hunt and Hess scale 4 or 5 for ruptured aneurysms 9. Intended use of a flow diverting stent (e.g. pipeline) 10. Subject has concurrent intracranial pathology, e.g. * Moyamoya * Vasculitis documented by biopsy results * AVMs * AV fistulas * Significant atherosclerotic disease (i.e. symptomatic and or \>50% narrowing of the parent arteries necessary to traverse in order to coil the target aneurysm) * Intracranial Hematoma (unrelated to the target aneurysm) * Brain tumors * Vascular tortuosity and other conditions preventing access to target aneurysm 11. Subject has serious co-morbidities that could confound the study results: * Uncontrolled hypertension * Uncorrectable coagulation abnormality * Contraindications for heparin, aspirin or clopidogrel * Uncontrolled Diabetes Mellitus * Organ failure of kidney, liver, heart, or lung * Myocardial infarction within the past 6 months * Cancer likely to cause death within 2 years or less. 12. Subject history indicates high risk of non-compliance (e.g., substance abuse, psychosocial issues, etc.) 13. Subject has a known history contraindicating contrast dye or iodine that cannot be pre-medicated prior to coiling procedure (vs. sensitivity which can be safely controlled by antihistamine, steroid, etc.). Medical clearance will be needed for this issue. 14. Patients who are unable to complete scheduled follow up assessments at the enrolling center due to limited life expectancy (\<2 years), co-morbidities or geographical considerations 15. Subject is currently breast feeding, pregnant or plans to become pregnant in the next 2 years. 16. Major surgical procedure or trauma within 30 days prior to randomization 17. The patient is currently enrolled in another clinical study (device or drug). 18. More than one aneurysm needing treatment at the same time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Aneurysm Recurrence Post Surgery | post surgery to 24 months | Defined as any progression on the Raymond-Roy (RR) Aneurysm Occlusion Scale. The RR scale is such that 1=complete occlusion, 2=residual neck, and 3=residual aneurysm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Outcome: Modified Rankin Scale (mRS) | 24 months | modified rankin scale is a measure of neurological disability, which ranges from 0=no symptoms to 5=severe disability (6=dead). |
| Number of Participants With Adverse Events Related to the Procedure and/or the Device by Participant at Any Time in the Study. | 24 months | number of participants who experienced any peri-procedural or post-procedural Adverse Event noted to be related to the procedure or device. |
| Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. | 24 months | total number of Adverse Events per person that were noted to be related to the procedure and device during the study |
| Number of Patients Who Expired During the Study (Mortality Rate) | 24 months | all-cause mortality at any time during study follow-up |
| Packing Density | at operation | Packing density as measured by volumetric filling of the aneurysm |
| Number of Patients Who Needed Re-treatment of Target Aneurysm | 24 months | During the 24 month follow-up, if Aneurysm needed to be re-treated. |
| Number of Participants Experiencing a Hemorrhage From Target Aneurysm Post Surgery | 24 months | Per the Adverse event log, if a hemorrhage or rupture occurred that was noted to be related to the procedure or device at any point during the 24 month follow-up (not during the operation). |
| Number of Participants Who Progressed on the Meyers Scale | 24 months | Occlusion (in)stability was determined by progression on the Meyers scale. The Meyer scale is a 6-point grading scale based on the percentage of the aneurysm filled by contrast on DSA. Grade zero indicates complete and total aneurysm occlusion without remnant or in-terstitial filling within the aneurysm. Grade 1 represents greater than 90%volumetric occlusion of the aneurysm based on planar imaging assessment; grade 2, 70%-89% aneurysm occlusion; grade 3,50%-69%; grade 4, 25%-49%; and grade 5, less than 25% volumetric aneurysm occlusion. |
| Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. | 24 months | Major recurrence is defined as progression on the Raymond-Roy (RR) Scale to 3, or if initial RR was 3, then progression on the Meyers scale. Minor recurrence was defined as a progression on the RR scale to 2. The RR scale is a 3 point measure of occlusion, 1=total, 2=residual neck, and 3=residual aneurysm. The Meyer scale is a 6-point grading scale based on the percentageof the aneurysm filled by contrast on DSA. Grade zero indicates complete and total aneurysm occlusion without remnant or in-terstitial filling within the aneurysm. Grade 1 represents \>90%volumetric occlusion of the aneurysm based on planar imaging assessment; grade 2, 70%-89% aneurysm occlusion; grade 3,50%-69%; grade 4, 25%-49%; and grade 5, \<25% volumetric aneurysm occlusion. |
| Number of Participants With Initial Complete Occlusion | at procedure | Raymond-Roy (RR) Scale=1 at procedure The RR scale is such that 1=complete occlusion, 2=residual neck, and 3=residual aneurysm. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HydroCoil Embolic System Aneurysm treatment using the HydroCoil Embolization System (21 CFR 882.5950)
HydroCoil Embolic System: HydroCoil Embolic System | 297 |
| Control Aneurysm treatment using bare platinum coil(s)
Control (bare platinum coils): bare platinum coils | 303 |
| Total | 600 |
Baseline characteristics
| Characteristic | Control | Total | HydroCoil Embolic System |
|---|---|---|---|
| Age, Continuous | 56.9 years STANDARD_DEVIATION 10.3 | 56.7 years STANDARD_DEVIATION 10.9 | 56.5 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 247 Participants | 490 Participants | 243 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 98 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 12 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 14 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 59 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 12 Participants | 4 Participants |
| Race (NIH/OMB) White | 247 Participants | 490 Participants | 243 Participants |
| Sex: Female, Male Female | 236 Participants | 474 Participants | 238 Participants |
| Sex: Female, Male Male | 67 Participants | 126 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 297 | 9 / 303 |
| other Total, other adverse events | 118 / 297 | 140 / 303 |
| serious Total, serious adverse events | 61 / 297 | 69 / 303 |
Outcome results
Primary
Number of Patients With Aneurysm Recurrence Post Surgery
Defined as any progression on the Raymond-Roy (RR) Aneurysm Occlusion Scale. The RR scale is such that 1=complete occlusion, 2=residual neck, and 3=residual aneurysm.
Time frame: post surgery to 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HydroCoil Embolic System | Number of Patients With Aneurysm Recurrence Post Surgery | 11 participants |
| Control | Number of Patients With Aneurysm Recurrence Post Surgery | 41 participants |
Comparison: A intent to treat analysis was performed, using multiple imputation methods.p-value: 0.00295% CI: [1.36, 3.97]Regression, Logistic
p-value: <0.0195% CI: [1.99, 7.92]Chi-squared
Secondary
Clinical Outcome: Modified Rankin Scale (mRS)
modified rankin scale is a measure of neurological disability, which ranges from 0=no symptoms to 5=severe disability (6=dead).
Time frame: 24 months
Population: Based on participants with any post procedural follow-up.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HydroCoil Embolic System | Clinical Outcome: Modified Rankin Scale (mRS) | Slight disability (mRS=2) | 24 Participants |
| HydroCoil Embolic System | Clinical Outcome: Modified Rankin Scale (mRS) | Moderately severe disability (mRS=4) | 2 Participants |
| HydroCoil Embolic System | Clinical Outcome: Modified Rankin Scale (mRS) | No significant disability (mRS=1) | 60 Participants |
| HydroCoil Embolic System | Clinical Outcome: Modified Rankin Scale (mRS) | Severe disability (mRS=5) | 0 Participants |
| HydroCoil Embolic System | Clinical Outcome: Modified Rankin Scale (mRS) | Moderate disability (mRS=3) | 13 Participants |
| HydroCoil Embolic System | Clinical Outcome: Modified Rankin Scale (mRS) | Expired (mRS=6) | 7 Participants |
| HydroCoil Embolic System | Clinical Outcome: Modified Rankin Scale (mRS) | No symptoms (mRS=0) | 181 Participants |
| Control | Clinical Outcome: Modified Rankin Scale (mRS) | Expired (mRS=6) | 9 Participants |
| Control | Clinical Outcome: Modified Rankin Scale (mRS) | No symptoms (mRS=0) | 178 Participants |
| Control | Clinical Outcome: Modified Rankin Scale (mRS) | No significant disability (mRS=1) | 63 Participants |
| Control | Clinical Outcome: Modified Rankin Scale (mRS) | Slight disability (mRS=2) | 28 Participants |
| Control | Clinical Outcome: Modified Rankin Scale (mRS) | Moderate disability (mRS=3) | 10 Participants |
| Control | Clinical Outcome: Modified Rankin Scale (mRS) | Moderately severe disability (mRS=4) | 0 Participants |
| Control | Clinical Outcome: Modified Rankin Scale (mRS) | Severe disability (mRS=5) | 4 Participants |
p-value: 0.578Wilcoxon (Mann-Whitney)
Secondary
Number of Participants Experiencing a Hemorrhage From Target Aneurysm Post Surgery
Per the Adverse event log, if a hemorrhage or rupture occurred that was noted to be related to the procedure or device at any point during the 24 month follow-up (not during the operation).
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HydroCoil Embolic System | Number of Participants Experiencing a Hemorrhage From Target Aneurysm Post Surgery | 2 Participants |
| Control | Number of Participants Experiencing a Hemorrhage From Target Aneurysm Post Surgery | 0 Participants |
p-value: 0.245Fisher Exact
Secondary
Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up.
Major recurrence is defined as progression on the Raymond-Roy (RR) Scale to 3, or if initial RR was 3, then progression on the Meyers scale. Minor recurrence was defined as a progression on the RR scale to 2. The RR scale is a 3 point measure of occlusion, 1=total, 2=residual neck, and 3=residual aneurysm. The Meyer scale is a 6-point grading scale based on the percentageof the aneurysm filled by contrast on DSA. Grade zero indicates complete and total aneurysm occlusion without remnant or in-terstitial filling within the aneurysm. Grade 1 represents \>90%volumetric occlusion of the aneurysm based on planar imaging assessment; grade 2, 70%-89% aneurysm occlusion; grade 3,50%-69%; grade 4, 25%-49%; and grade 5, \<25% volumetric aneurysm occlusion.
Time frame: 24 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HydroCoil Embolic System | Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. | Major recurrence | 32 Participants |
| HydroCoil Embolic System | Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. | Minor recurrence | 2 Participants |
| HydroCoil Embolic System | Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. | No major/minor recurrence | 217 Participants |
| Control | Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. | Major recurrence | 55 Participants |
| Control | Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. | Minor recurrence | 14 Participants |
| Control | Number of Participants Experiencing Major Versus Minor Recurrence by 24 Months Follow-up. | No major/minor recurrence | 197 Participants |
p-value: <0.01Chi-squared
Secondary
Number of Participants Who Progressed on the Meyers Scale
Occlusion (in)stability was determined by progression on the Meyers scale. The Meyer scale is a 6-point grading scale based on the percentage of the aneurysm filled by contrast on DSA. Grade zero indicates complete and total aneurysm occlusion without remnant or in-terstitial filling within the aneurysm. Grade 1 represents greater than 90%volumetric occlusion of the aneurysm based on planar imaging assessment; grade 2, 70%-89% aneurysm occlusion; grade 3,50%-69%; grade 4, 25%-49%; and grade 5, less than 25% volumetric aneurysm occlusion.
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HydroCoil Embolic System | Number of Participants Who Progressed on the Meyers Scale | 33 Participants |
| Control | Number of Participants Who Progressed on the Meyers Scale | 71 Participants |
p-value: <0.01Chi-squared
Secondary
Number of Participants With Adverse Events Related to the Procedure and/or the Device by Participant at Any Time in the Study.
number of participants who experienced any peri-procedural or post-procedural Adverse Event noted to be related to the procedure or device.
Time frame: 24 months
Population: Intent to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HydroCoil Embolic System | Number of Participants With Adverse Events Related to the Procedure and/or the Device by Participant at Any Time in the Study. | 64 Participants |
| Control | Number of Participants With Adverse Events Related to the Procedure and/or the Device by Participant at Any Time in the Study. | 75 Participants |
p-value: 0.352Chi-squared
Secondary
Number of Participants With Initial Complete Occlusion
Raymond-Roy (RR) Scale=1 at procedure The RR scale is such that 1=complete occlusion, 2=residual neck, and 3=residual aneurysm.
Time frame: at procedure
Population: Raymond-Roy Scale recorded at procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HydroCoil Embolic System | Number of Participants With Initial Complete Occlusion | 50 Participants |
| Control | Number of Participants With Initial Complete Occlusion | 82 Participants |
p-value: 0.003Chi-squared
Secondary
Number of Patients Who Expired During the Study (Mortality Rate)
all-cause mortality at any time during study follow-up
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HydroCoil Embolic System | Number of Patients Who Expired During the Study (Mortality Rate) | 7 Participants |
| Control | Number of Patients Who Expired During the Study (Mortality Rate) | 9 Participants |
p-value: 0.641Chi-squared
Secondary
Number of Patients Who Needed Re-treatment of Target Aneurysm
During the 24 month follow-up, if Aneurysm needed to be re-treated.
Time frame: 24 months
Population: participants with available followup
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HydroCoil Embolic System | Number of Patients Who Needed Re-treatment of Target Aneurysm | 13 Participants |
| Control | Number of Patients Who Needed Re-treatment of Target Aneurysm | 22 Participants |
p-value: 0.162Chi-squared
Secondary
Packing Density
Packing density as measured by volumetric filling of the aneurysm
Time frame: at operation
Population: Participants with both imaging data (to determine aneurysm size), and coil information (length, number, and type used)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HydroCoil Embolic System | Packing Density | 32.5 density as expressed as a percentage | Standard Deviation 14.8 |
| Control | Packing Density | 24.7 density as expressed as a percentage | Standard Deviation 10.2 |
p-value: <0.01t-test, 2 sided
Secondary
Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device.
total number of Adverse Events per person that were noted to be related to the procedure and device during the study
Time frame: 24 months
Population: Intent to treat population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HydroCoil Embolic System | Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. | No events | 233 Participants |
| HydroCoil Embolic System | Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. | One event | 44 Participants |
| HydroCoil Embolic System | Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. | Two events | 19 Participants |
| HydroCoil Embolic System | Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. | Three events | 1 Participants |
| Control | Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. | Three events | 4 Participants |
| Control | Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. | No events | 228 Participants |
| Control | Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. | Two events | 8 Participants |
| Control | Total Number of Peri-procedural and Post-procedural Adverse Events Related to the Procedure and/or the Device. | One event | 63 Participants |
p-value: 0.769Cochran-Armitage Trend Test