|
|
| General |
| Study Status |
Completed |
| 522 Number / Requirement Number |
PS100001 / PSS002 |
| Date Original Plan Accepted |
05/31/2012
|
| Date Current Plan Accepted |
07/21/2015
|
| Study Name |
HydroSoft/HydroFrame Study
|
| Device Name |
Microvention hydrocoil-soft-frame
|
| Root Document Number |
K020434
K032590
K033836
K041551
K050954
K070656
K080666
K090357
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
External Registry
|
| Comparison Group |
Objective Performance Criterion
|
| Analysis Type |
Analytical
|
| Study Population |
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
Retrospective and prospective, multi-center, single arm study with two study groups.
Primary hypothesis #1(#2):
Null Hypothesis: PHC ¡Ý PBPC + 0.029
Alternative Hypothesis: PHC < PBPC + 0.029
Where PHC (PBPC) is the proportion of hydrocephalus (aseptic meningitis) cases in patients provided the HydroSoft / HydrFrame (Bare Platinum Coil).
|
| Study Population |
The study subjects are patients with unruptured intracranial aneurysms who are candidates for endovascular coil embolization and who have received HydroSoft/HydroFrame alone or a combination of HydroSoft/HydroFrame and bare platinum coils. However, to be included in the study, the patients must receive > 50% coil length of HydroSoft/HydroFrame. Patients who have received HydroCoil or bioactive coils will be excluded from the study.
|
| Sample Size |
A total of 294 patients who will be provided with the HydroSoft/HydroFrame device will be enrolled in the study. Up to an additional 33 patients may be enrolled to account for any subjects lost to follow-up (total 327 patients).
Unexplained hydrocephalus and/or aseptic meningitis.
|
| Key Study Endpoints |
Unexplained hydrocephalus and/or aseptic meningitis.
|
| Follow-up Visits and Length of Follow-up |
In the HEAT study, patients will be followed at discharge, 3-28 days, 3-12 months and 18-24 months post-treatment. The discharge follow-up visit will include a clinical and neurological assessment. The 3-28 day follow-up visit will include a clinical and neurological assessment. The 3-12 month follow-up visit will include a clinical, neurological and angiographic assessment. The 18-24 month follow-up visit will include a clinical, neurological and angiographic assessment. At each follow-up visit, any new and unresolved adverse events including hydrocephalus and aseptic meningitis will be documented. In addition, any reported adverse events will be documented during unscheduled follow-up visits.
In the GREAT study, patients will be followed at discharge, 6 months and 18 months post- treatment. The discharge follow-up visit will include a clinical and neurological assessment. The
6-month and 18-month follow-up visits will include a clinical, neurological and angiographic follow-up. At each follow-up visit, any new and unresolved adverse events including hydrocephalus and aseptic meningitis will be documented. In addition, any reported adverse events will be documented during unscheduled follow-up visits.
Because 1) there were no reports of unexplained hydrocephalus or aseptic meningitis in the 305 patients from the GREAT study and the HEAT study, and in the over 260,000 HydroSoft/HydroFrame coils marketed by the sponsor or in the published literature. 2) Although there were reports of unexplained hydrocephalus (0.8-1.9%) and aseptic meningitis (0.3%) related to the use of the HydroCoil coils, the rate was determined to be statistically non-inferior to that for bare platinum coils, given comparable patient populations. In the FDA letter dated May 30, 2014, FDA determined that the 522 postmarket surveillance study requirements for the HydroCoil coils had been fulfilled. Microvention requested to terminate the 522 study. FDA approved the requested and instructed the sponsor to submit a final report to close the study on July 21.
FDA has previously indicated that the incidence of unexplained hydrocephalus in unruptured aneurysms is between 1.0-2.0 %. This is based on the information from the published literature and data from the HELPS study. The HELPS study reported one case of hydrocephalus among 115 patients with unruptured aneurysms in the bare platinum coil group (0.85%, 95% Cal: 0.044%, 4.2%). Approximately 15,000 patients have been treated with the HydroSoft Hydro Frame with no reports of hydrocephalus or aseptic meningitis. In addition, over 900 patients have been treated with the HydroSoft/HydroFrame in various registries/studies with no reports of hydrocephalus or aseptic meningitis. In light of these reports and the FDA suggestion regarding the incidence of hydrocephalus with bare platinum coils, MicroVention proposes as a standard an 18-month incidence of 1.5% for both hydrocephalus and aseptic meningitis. The 1.5% was used to calculate the sample size. The estimates of hydrocephalus and aseptic meningitis and their 95% Blyth-Styli Casella confidence interval in patients provided the HydroSoft/HydroFrame devices will be calculated. For each outcome, if the upper bound is ¡Ü 0.044, the hypothesis is rejected and non-inferiority concluded.
|
| Interim or Final Data Summary |
| Interim Results |
There have been no reports of hydrocephalus or aseptic meningitis in the HEAT study.
|
| Actual Number of Patients Enrolled |
305
|
| Actual Number of Sites Enrolled |
67
|
| Patient Followup Rate |
96%
|
| Final Safety Findings |
There is no evidence in support of an association between implanting HydroSoft/HydroFrame and hydrocephalus or aseptic meningitis . There were no reports of unexplained hydrocephalus or aseptic meningitis in the 305 patients from the GREAT study and the HEAT study, and in the over 260,000
HydroSoft/HydroFrame coils marketed by the sponsor or in the published literature
|
| Final Effectiveness Findings |
No effectiveness endpoint was evaluated in the 522 study
|
| Study Strengths and Weaknesses |
Strengths: Accurate patient information was collected from prospective cohort study
Weaknesses: The study is a single arm study against historical control. Patients in the treatment arm are derived from two separate clinical studies and prospectively followed. The rates of hydrocephalus (or aseptic meningitis) in patients treated with Bare Platinum Coil of the control arm were estimated from previous medical experience. Therefore, confounding factors cannot be well controlled in the single arm study and confounding bias could not be ruled out. Conclusion
to be drawn from the study must be interpreted with caution
|
| Recommendations for Labeling Changes |
The study will be closed as Completed; no labeling change is recommended.
|
