|
|
| General |
| Study Status |
Ongoing |
Application Number /
Requirement Number |
P170043 / PAS001 |
| Date Original Protocol Accepted |
04/16/2019
|
| Date Current Protocol Accepted |
04/30/2020
|
| Study Name |
Extended f/u Premarket Cohort
|
| Device Name |
iStent inject Trabecular Micro-Bypass System (Model G2-M-IS)
|
| Clinical Trial Number(s) |
NCT01461291
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
Objective Performance Criterion
|
| Analysis Type |
Analytical
|
| Study Population |
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
The objective of this post approval study (PAS) is to evaluate the long -term rate of clinically relevant complications associated with iStent inject® placement and stability in subjects who have completed participation of the IDE clinical trial (GC-008). This is a long-term safety, multicenter, observational study with no planned interventions.
|
| Study Population |
Randomized subjects in the GC-008 study who are able to understand the study requirements, willing to follow study instructions and are willing to return for required study follow-up visits.
|
| Sample Size |
Up to 475 eyes of 475 subjects. This is based on the number of randomized subjects who consented to 36-month follow-up in study Protocol the GC-008 and study followed for 24 months. Subjects will need to meet the study inclusion criteria.
|
| Key Study Endpoints |
Safety Endpoint:
The rate of clinically relevant complications associated with iStent inject placement and stability as determined at 60 months. Specific
device-related complications include clinical sequelae resulting from device position including, but not limited to:
Secondary surgical intervention (SSI) to modify device position
(e.g., repositioning or explantation)
Corneal endothelial touch by device
Corneal edema leading to best-spectacle corrected visual acuity
loss (BSCVA loss) > 2 lines at the Month 60 visit, in comparison
with preoperative BSCVA
Other Safety Outcomes:
Rate of occurrence of sight-threatening adverse events including:
Persistent (at time of study exit) BSCVA loss = 3 lines
compared to best recorded BSCVA at any postoperative visit
Endophthalmitis
Corneal decompensation
Retinal detachment
Severe choroidal hemorrhage or detachment or aqueous misdirection
Rate of ocular secondary surgical interventions (SSI)
Rate of other adverse events including:
Increase from baseline IOP of greater than or equal to 10 mmHg at any time greater than or equal to 30 days postoperative
BSCVA loss greater than or equal to 2 lines at Month 60 compared to screening
BSCVA loss greater than or equal to 2 lines at Month 60 compared to best recorded
BSCVA at any postoperative visit
Device movement, defined as a stent not visible in the original location, that does not result in clinically relevant complications as described above (e.g., SSI to modify device position, corneal endothelial touch by device, or corneal edema leading to BSCVA loss > 2 lines at the Month 60 visit
compared to preoperative BSCVA), and that is not attributable to any one or more of the following:
- variations in gonioscopy, optical coherence tomography
(OCT) or ultrasonic biomicroscopy (UBM) (or other standard imaging methods) viewing angle or illumination
- changes in angle anatomy due to concomitant findings such as resolution of hyphema
- changes in anterior chamber depth
- development of focal peripheral anterior synechiae (PAS)
|
| Follow-up Visits and Length of Follow-up |
60 months post-randomization in the IDE trial
|
| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
227
|
| Actual Number of Sites Enrolled |
24
|
| Patient Follow-up Rate |
Of the 475 potential subjects, 47.8% (227/475) (178 iStent, 49 control participants) were enrolled in this extended follow-up study. 100% of the participants completed the fifth year follow-up.
|
| Final Safety Findings |
The cumulative rate of postoperative adverse events (AEs) was 56.5% (218/386) in the iStent group (452 AEs in 218 participant) and 59.7% (71/119) in the control group (173 AEs in 71 participants). The cumulative rates of sight-threatening AEs (e.g., endophthalmitis, corneal decompensation, retinal detachment, several choroidal hemorrhage, or aqueous misdirection) was 24.4% (94/386) in the iStent group and 34.5% (41/119) in the control group.
The cumulative rate of secondary surgical interventions (SSIs) was 12.2% (47/386) in the iStent group (56 SSIs in 47 participants) and 16% (19/119) in the control group (24 SSIs in 19 participants). The most frequently-reported SSI in both groups was selective laser trabeculoplasty (SLT; 22 SLTs in 20 participants in iStent group, 15 SLTs in 14 participants in control group). IOP-lowering SSIs (including canaloplasty, laser trabeculoplasty, trabeculectomy, and XEN stent implantation) were performed in 8.5% (33/386) of the iStent group and 15.1% (18/119) of the control group. 30 secondary surgical interventions (SSIs) that occurred after Month 36 were reported for 23 participants (12.9%) in the iStent inject group, and 16 SSIs were reported for 14 subjects (28.6%) in the control group. Laser for iStent obstruction was performed in four iStent participants. There were no iStent explantations.
At Month 60, one iStent (0.6%, 1/178) and two control (4.1%, 2/49) participants had BSCVA loss =2 lines compared to at screening. These AEs were not device-related.
The cumulative rate of non-visible (“deep”) iStents on gonioscopy (at the last three visits of GC-008) was 1.0% (4/386). Non-visualization of iStents on gonioscopy was reported for one iStent participant at Month 60, who did not follow up for recommended ultrasound biomicroscopy imaging. The cumulative rate of peripheral anterior synechiae reported on gonioscopy was 13.8%. One iStent participant had suspected iStent obstruction at Month 59 and underwent a subsequent laser procedure as an SSI.
Corneal edema persisting for =30 days was reported in one iStent participant (0.3%, 1/386) and none in the control group. The mean percent change in endothelial cell density (ECD) from baseline to Month 60 was -14.3% (SD 13.4) for the iStent inject group and -14.8% (SD 10.3%) for the control group. The percentage of eyes with an endothelial cell loss (ECL) >30% at the Month 60 visit was 9.4% (16/170) in the iStent inject group and 6.3% (3/48) in the control group. The difference in the rate of ECL > 30% was estimated as 3.16%, 95% CI (-5.0%, 11.3%) and was not statistically or clinically significant.
46 minor protocol deviations (PDs) were reported due to out-of-window Month-60 visits (N=24), protocol-specified assessments not performed (N=26), and intraocular pressure assessment not performed per protocol (N=4).
|
| Final Effect Findings |
No effectiveness findings were reported
|
| Study Strengths & Weaknesses |
Strengths: The information from this continuation post-approval study (PAS) that provides additional long-term extended follow-up data for the iStent inject.
Weaknesses: There was a 100% missing data rate at the Month 48 visit and most visits were out-of-window by at least 6 months or longer. Fewer than half of the original pivotal cohort enrolled in this continuation PAS. This PAS was not statistically powered for any safety endpoints.
|
| Recommendations for Labeling Changes |
yes
|
