A Study to Assess Long-Term Safety of the CyPass Micro-Stent in Patients Completing the COMPASS Trial

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety of the CyPass Micro-Stent in subjects who completed Study Protocol TMI-09-01, COMPASS Trial.

Detailed Description
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The COMPASS Trial (TMI-09-01) was a prospective, randomized, comparative multicenter study to assess the safety and effectiveness of the CyPass Micro-Stent in subjects with primary open angle glaucoma who were undergoing cataract surgery. In the study, 505 subjects were randomized to either the CyPass group, who underwent cataract surgery and received the CyPass Micro-Stent, or the Control group, who underwent cataract surgery alone. All subjects randomized were to be followed for 2 years postoperatively. Four hundred eighty (480) subjects completed this study. The COMPASS-XT (TMI-09-01-E) Trial is designed to collect safety data beyond 24 months postoperatively for subjects who completed the COMPASS Trial. In COMPASS-XT, clinical data will be collected at 36 months, 48 months, and 60 months postoperatively for a total of 5 year follow-up across the 2 studies.

Official Title
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An Observational Multicenter Clinical Study to Assess the Long-Term Safety of the CyPass Micro-Stent in Patients With Primary Open Angle Glaucoma Who Have Completed Participation in the COMPASS Trial

Conditions
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Primary Open Angle Glaucoma (POAG)

Intervention / Treatment
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* Device: CyPass Micro-Stent
* Procedure: Cataract Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed the COMPASS Trial Understands study requirements and is willing to follow study instructions and return for study visits Exclusion Criteria: Systemic disease that would put subject health at risk and/or prevent completion of required study visits. Early termination from the COMPASS Trial.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cataract Surgery + CyPass<br>CyPass Micro-Stent implanted at the conclusion of cataract surgery (COMPASS trial) | Device: CyPass Micro-Stent<br>* The CyPass Micro-Stent is a small tube with a through-lumen designed to redirect aqueous fluid from the front into the back of the eye. The device is implanted after completion of cataract surgery.<br>Procedure: Cataract Surgery<br>* Cataract surgery involves the removal of the natural lens, which has become clouded (called a cataract), and insertion of an artificial lens (called an intraocular lens). This procedure is done through a small surgical incision in the eye.<br>|
| Active Comparator: Cataract Surgery Only<br>Cataract Surgery (COMPASS trial) with no CyPass Micro-Stent implantation | Procedure: Cataract Surgery<br>* Cataract surgery involves the removal of the natural lens, which has become clouded (called a cataract), and insertion of an artificial lens (called an intraocular lens). This procedure is done through a small surgical incision in the eye.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year Annualized Rate (Percentage) of Sight-threatening Adverse Events, by Treatment Group | Sight-threatening adverse events occurring in the study eye included, but were not limited to: BCVA loss of ≥ 3 lines, endophthalmitis, corneal decompensation, severe retinal detachment, severe choroidal hemorrhage, severe choroidal detachment and aqueous misdirection. The number of events at the end of Year 5 was divided by the number of eyes at risk at the beginning of Year 1 for a 5-year annualized rate. The 5-year annualized rate is reported as a percentage, with the last annual non-censored rate divided by 5. Inferential testing was not planned for this endpoint. | Up to Month 60 postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects According to Best Corrected Visual Acuity (BCVA) by Visit | Best corrected (with spectacles or other visual corrective devices) VA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) charts at 1 or 4 meters and determined by total number of letters read correctly. 20/20 Snellen is considered 'normal' vision. A larger denominator indicates a lower visual acuity. Baseline, Month 12, and Month 24 data derived from previous COMPASS trial. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Baseline, Month 12, 24, 36, 48, 60 postoperative | 
| Number of Subjects Who Reported at Least One Protocol-specified Ocular Adverse Event in the Study Eye | Ocular adverse events in the study eye could include, but were not limited to, BCVA loss of 2 lines (10 letters) or more on the ETDRS chart in comparison with the best BCVA reported in Study Protocol TMI-09-01, endophthalmitis, corneal edema, and corneal decompensation. Inferential testing was not planned for this endpoint. | Up to Month 60 postoperative | 
| Slit-lamp Examination Results at Visits 36, 48, and 60, by Treatment Group - Corneal Edema | Corneal Edema (swelling of the cornea) was assessed by the investigator during slit-lamp examination and rated on a 4-point scale: None (transparent and clear or less than mild), Mild (dull glassy appearance), Moderate (Dull glassy appearance of epithelium with large number of vacuoles), and Severe (epithelial bullae and/or stromal edema, localized or diffuse, with or without stromal striae). Only the categories with reported data are included. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Slit-lamp Examination Results at Visits 36, 48, and 60, by Treatment Group - Corneal Staining/Erosion | Corneal Staining (appearance of tissue disruption and other pathophysiological changes) and erosion (abrasion) were assessed by the investigator during slit-lamp examination and rated on a 4-point scale: None (no fluorescein staining of epithelium, OR less than mild), Mild (slight fluorescein staining confined to a small focus), Moderate (regionally dense fluorescein staining (1 mm or greater in diameter) with underlying structure moderately visible), and Severe (marked fluorescein staining or epithelial loss). Only the categories with reported data are included. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Slit-lamp Examination Results at Visits 36, 48, and 60, by Treatment Group - Anterior Chamber Cells | Inflammatory anterior chamber cells (cells in the front portion of the eye) were assessed by the investigator during slit-lamp examination and reported in one of 6 categories according to cells per 1x1 mm slit: 0-<1 cell, 1-5 cells, 6-15 cells, 16-25 cells, and 26-50 cells, and >50 cells. Only the categories with reported data are included. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Slit-lamp Examination Results at Visits 36, 48, and 60, by Treatment Group - Anterior Chamber Flare | Anterior Chamber Flare (protein escaping from dilated vessels) was assessed by the investigator during slit-lamp examination and rated on a 5-point scale: None, Faint, Moderate (iris and lens details clear), Marked (iris and lens details hazy), and Intense (fibrin or plastic aqueous). The presence of flare is a sign of intraocular inflammation. Only the categories with reported data are included. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Slit-lamp Examination Results at Visits 36, 48, and 60, by Treatment Group - Iris Atrophy/Erosion | Iris Atrophy/Erosion (deterioration) was assessed by the investigator during slit-lamp examination and rated on a 4-point scale: None, Mild, Moderate, and Severe. Only the categories with reported data are included. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Slit-lamp Examination Results at Visits 36, 48, and 60, by Treatment Group - Iris Peaking | Iris Peaking (one part of the iris pulled to a peak resulting in an irregular pupil) was assessed by the investigator during slit-lamp examination and rated on a 4-point scale: None, Mild, Moderate, and Severe. Only the categories with reported data are included. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Slit-lamp Examination Results at Visits 36, 48, and 60, by Treatment Group - Iris Rubeosis | Iris Rubeosis (abnormal blood vessels (formed by neovascularization) found on the surface of the iris) was assessed by the investigator during slit-lamp examination and rated on a 4-point scale: None, Mild, Moderate, and Severe. Only the categories with reported data are included. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Slit-lamp Examination Results at Visits 36, 48, and 60, by Treatment Group - Posterior Capsule Opacification (PCO) Severity | PCO (cloudy layer of scar tissue behind the lens implant) Severity was assessed by the investigator during slit-lamp examination and rated on a 6-point scale: None, Minimal, Mild, Moderate, Severe, and Unspecified. Only the categories with reported data are included. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Gonioscopy at Visits 36, 48, and 60, CyPass Subjects Only | For subjects in the CyPass group, gonioscopic examination was performed to assess the position of the CyPass Micro-Stent in the angle and with respect to the iris and the corneal endothelium. A visible CyPass Micro-Stent indicated a lack of adhesions (favorable). One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Number of Subjects With Clinically Significant Findings Noted During Fundus Examinations | The dilated fundus examination was performed by the investigator to evaluate the health of the vitreous, retina, macula, choroid, and optic nerve. Clinically significant findings are reported categorically. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative | 
| Change From Month 24 in Visual Field Mean Deviation | Visual field (how much one can see to each side while focusing the eyes on a central point (peripheral vision)) deviations were obtained with a Humphrey automated perimeter using the 24-2 SITA standard testing method. Normal deviation values are typically within 0 to -2 decibels (dB) and become more negative as the overall field worsens. Month 24 data derived from COMPASS trial. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 24, 36, 48, 60 postoperative | 
| Change From Month 24 in Central Corneal Thickness | Central corneal thickness was evaluated by Pachymetry and measured in micrometers (μm). A negative number indicates a decrease in corneal thickness (unfavorable). Month 24 data derived from COMPASS trial. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 24, 36, 48, 60 postoperative | 
| Central Corneal Endothelial Cell Density (ECD) by Visit | The endothelium maintains corneal hydration and reduced cell density can disrupt vision. Central endothelial cell counts were assessed using non-contact specular microscopy. Specular images were taken of the corneal endothelium and submitted to a reading center in order to standardize readings across all sites and optimize reading reliability. Baseline through Month 24 data were derived from COMPASS trial. A higher cell density indicates improvement. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Baseline, Month 3, 6, 12, 24, 36, 48, 60 postoperative | 
| Number of Subjects With CyPass Device Malposition, Dislodgement or Movement | Device position was a qualitative and subjective assessment by the investigator and evaluated based on visible number of rings of the device under the gonioscopic exam. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. This outcome measure was prespecified for Cataract Surgery + CyPass arm only. | Up to 60 months postoperatively | 
| Mean Reduction From Baseline in Intraocular Pressure (IOP) | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A higher reduction from baseline (ie, a greater postitive number) indicates greater improvement. Baseline was derived from COMPASS trial. One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Baseline, Month 36, 48, 60 postoperative | 
| Percentage of Subjects With ≥ 20% Reduction in IOP From Baseline (COMPASS Trial) Without the Use of Ocular Hypotensive Medications | IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry. A higher IOP can be a greater risk for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Baseline, Month 36, 48, 60 postoperative | 
| Percentage of Subjects Not Using Ocular Hypotensive Medication With IOP ≥ 6 mmHg and ≤ 18 mmHg | IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry. A higher IOP can be a greater risk for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis. Inferential testing was not planned for this endpoint. | Month 36, 48, 60 postoperative |