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| General |
| Study Status |
Ongoing |
Application Number /
Requirement Number |
P170043 / PAS002 |
| Date Original Protocol Accepted |
04/16/2019
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| Date Current Protocol Accepted |
03/03/2021
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| Study Name |
New Enrollment PAS
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| Device Name |
iStent inject Trabecular Micro-Bypass System (Model G2-M-IS)
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Analytical
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
The objective of this post approval study (PAS) is to evaluate the rate of clinically relevant complications associated with iStent inject
placement and stability, as determined at 36 months in the postmarket setting compared to the pre-specified performance
target of 2%. This is a prospective, non-randomized, multicenter, single-arm, post approval study of the iStent inject with follow-up
through 3 years postoperative.
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| Study Population |
358 eyes at a minimum of 15 and up to 30 investigational sites in the U.S. It is expected that the enrollment phase will last up to 37.5
months.
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| Sample Size |
A sample size of 250 eyes can provide a statistical power of 80% at a true p of 0.05. Considering a drop-out rate of 30% at 36 months for
this post-approval study, the study should treat at least 358 eyes of 358 subjects.
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| Key Study Endpoints |
The rate of clinically relevant complications associated with iStent inject placement and stability as determined at 36 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 BSCVA loss > 2 lines at the Month 36 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 greater than or equal to 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 36 compared to preoperative
BSCVA loss greater than or equal to 2 lines at Month 36 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 36 visit compared to preoperative BSCVA), and that is not attributable to any one or more of the following:
variations in gonioscopy, OCT or 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)
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| Follow-up Visits and Length of Follow-up |
36 months (3 years)
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| Interim or Final Data Summary |
| Interim Results |
A total of 387 subjects were consented and enrolled at 14 sites, of which 367 subjects met all eligibility criteria and were implanted with the study devices. Enrollment is complete, and the last subject was treated on June 23, 2022.
Of those implanted, 64 subjects were implanted with iStent “inject” and 303 with iStent “inject W”. No intraoperative AEs were reported. Most were implanted with 2 stents; 2 subjects were implanted with 3 stents due to implantation difficulties and 1 subject was implanted with 1 stent. Implantation issues were reported for 30 other subjects, most due to injector not deploying and requiring second injector, others due to stent not adequately seated in the trabecular meshwork with some requiring second injector or forceps to complete placement.
107 postoperative study eye AEs were reported in 77/367 (21.0%) subjects. The most common was dry eye (16 subjects; 4.4%). Inflammation was reported in 11 subjects (3.0%); 8 events were mild and 3 were moderate in severity, all resolved. Stent obstruction by iris was reported for 1 subject (0.3%) at Week 1, not requiring treatment, follow-up is ongoing. Increased IOP (i.e., 2 events, IOP increase = 10 mmHg and IOP increase requiring oral medication) was reported for 1 subject, resolved; this subject experienced several AEs (inflammation, branch retinal vein occlusion, and macular edema).
At Month 12, 96.9% of subjects had Best Corrected Visual Acuity (BCVA) of 20/40 or better, 85% of 20/25 or better. Ten subjects had VA worse than 20/40 at last available visit, which includes 8 subjects with preoperative BSCVA worse than 20/40.
Moderate corneal edema was observed transiently at Day 1 postop in 14 eyes (3.8%); severe corneal edema was observed in 1 subject on Day 1 only. Mild corneal edema was observed in 5 eyes (1.4%) at Month 1 and one eye (0.3%) at Month 12. There were no reports of moderate or severe corneal edema after the Day 1 visit.
Goniosynechiae were reported postoperatively in 7 subjects (6 by the same investigator), all of whom follow-up is ongoing. One subject had a deeply implanted stent noted on gonioscopy at Day 1 through Month 12, follow-up is ongoing (this subject was implanted with three stents). In subjects implanted with 2 stents, less than 2 stents were transiently not visible via gonioscopy in 11 eyes at Day 1 and/or Week 1 only.
Visual Field Mean Deviation (MD) worsening of = 2.5 dB was reported in 19 eyes (6.5%) at the Month 12 visit.
Endothelial cell density (ECD) loss >30% was reported for 37 eyes (11.8%) at Month 6, 16 eyes (7.6%) at Month 12, and none at Month 24 to date, follow-up is ongoing. Seven (7) subjects were reported with central ECD <1,000 or < 750 at any visit.
137 protocol deviations were reported for 102/367 subjects. Most common were out-of-window visits less than or equal to 7 days (n=30), specular microscopy not performed per protocol (n=20), and visual field not performed per protocol (n=18); other deviations included 9 missed visits, and 4 subjects in whom implantation was not performed per protocol.
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| Actual Number of Patients Enrolled |
387
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| Actual Number of Sites Enrolled |
14
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| Patient Follow-up Rate |
Accountability rates were reported as 97.8% (355/363) at Month 6, 98.7% (294/298) at Month 12, and 87.9% (29/33) at Month 24.
Follow-up is ongoing for remaining active subjects, 1 (0.3%) at Month 6, 64 (17.4%) at Month 12, and 328 (89.4%) at Month 24.
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| Study Strengths & Weaknesses |
Strength: This is a well-designed new enrollment post-approval study (PAS) that provides additional long-term safety data for the iStent inject and inject W.
Weakness: Summary analysis has not been provided to date for stents which are located in inappropriate position (e.g., deep, lost, dislocated), which can lead to ocular damage as a potential safety concern.
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