A Prospective, Multicenter, Randomized Comparison of the Hydrus to the iStent® for Lowering Intraocular Pressure in Primary Open Angle Glaucoma
Phase: NA
Conditions: Primary Open Angle Glaucoma, Pseudoexfoliative Glaucoma, Pigmentary Glaucoma
Sponsor: Ivantis, Inc.

Ivantis, Inc. 
Protocol NCT02023242 
 
Page 1 of 15 
 
 
 
 
 
A PROSPECTIVE, MULTICENTER, RANDOMIZED COMPARISON 
OF THE HYDRUSTM TO THE ISTENT™ FOR 
LOWERING INTRAOCULAR PRESSURE IN 
PRIMARY OPEN ANGLE GLAUCOMA  
(THE HYDRUS V TRIAL) 
 
 
07 MARCH 2012 
 
 
 
PROTOCOL #: NCT02023242 
 
 
 

 
Ivantis, Inc. 
Protocol NCT02023242 
 
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Table of Contents 
1.0 
DEVICE DESCRIPTION ........................................................................................3 
2.0 
STUDY OBJECTIVE AND DESIGN.....................................................................4 
3.0 
STUDY ENDPOINTS .............................................................................................5 
4.0 
STATISTICAL METHODS ....................................................................................5 
4.1 
Study Hypothesis ....................................................................................................5 
4.2 
Sample Size ............................................................................................................5 
4.3 
Safety Analysis .......................................................................................................5 
5.0 
STUDY POPULATION ..........................................................................................6 
5.1 
Inclusion Criteria ....................................................................................................6 
5.2 
Exclusion Criteria ...................................................................................................6 
6.0 
STUDY PROCEDURES .........................................................................................7 
6.1 
Subject Entry, Consent and Enrollment .................................................................7 
6.2 
Medication Wash Out .............................................................................................8 
6.3 
Goldmann Tonometry Procedure ...........................................................................8 
6.4 
Surgical Procedure .................................................................................................9 
6.5 
Perioperative Medication .......................................................................................9 
6.6 
Study Visits and Examination Schedule ..............................................................10 
6.7 
Unscheduled Visits ...............................................................................................10 
6.8 
Postoperative Ocular Hypotensive Medications ..................................................10 
6.9 
Subject Disposition ...............................................................................................11 
7.0 
ADVERSE EVENTS .............................................................................................11 
7.1 
Anticipated Adverse Events .................................................................................12 
7.2 
Intraoperative Adverse Events .............................................................................12 
7.3 
Postoperative Adverse Events ..............................................................................12 
7.4 
Recording and Reporting Adverse Events ...........................................................13 
7.5 
Grading of AEs .....................................................................................................14 
7.6 
Adverse Events Requiring Expedited Reporting ..................................................14 
7.7 
Unanticipated Adverse Device Effect ..................................................................14 
APPENDIX 1: SCHEDULE OF EVENTS AND PROCEDURES ...................................15 
 
 
 
 

 
Ivantis, Inc. 
Protocol NCT02023242 
 
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1.0 
DEVICE DESCRIPTION 
The Hydrus Aqueous Implant is a crescent-shaped implantable device pre-loaded onto a 
hand-held delivery system.  The Implant is delivered into Schlemm's canal by inserting 
the cannula of the delivery system through the trabecular meshwork and advancing the 
implant through the cannula.  Once the implant is in position, the central core wire of the 
delivery system is retracted, allowing complete detachment of the Hydrus Aqueous 
Implant.  Upon implantation, the crescent-shaped device provides a support structure, 
serving to dilate and restore the natural aqueous outflow pathway through Schlemm's 
canal, leading to a reduction of intraocular pressure. 
The Hydrus Aqueous Implant is composed of nitinol, a metal alloy composed of nearly 
equal parts of nickel (Ni) and titanium (Ti).  Nitinol has been used extensively in a 
variety of implantable vascular and orthopedic devices for its proven properties of 
flexibility, strength and biocompatibility.  As a shape memory alloy, nitinol has super 
elastic properties making it suitable as a support structure in Schlemm's canal.  Its 
flexibility and small size allow delivery of the Hydrus through torturous, restrictive 
passages with minimal force.  The Hydrus Aqueous Implant is illustrated in Figure 1, on 
the following page.  
 
 
 
 

 
Ivantis, Inc. 
Protocol NCT02023242 
 
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Figure 1: The HydrusTM Aqueous Implant 
 
 
 
 
 
2.0 
STUDY OBJECTIVE AND DESIGN 
The objective of this clinical trial is to compare the effectiveness of one Hydrus to two 
iStents for lowering intraocular pressure (IOP) in patients with mild-to-moderate primary 
open angle glaucoma (POAG), pseudoexfoliative glaucoma (PXG), or pigmentary 
glaucoma (PG). 
 
This study is a prospective, multicenter, single masked, randomized, clinical trial in 
which a total of 160 subjects (80 per study arm) will be treated with either one Hydrus or 
two iStents for treatment of POAG, PXG, or PG in subjects with a phakic lens.  The 
study will be conducted according the Declaration of Helsinki.  All study subjects must 
sign the Informed Consent prior to initiating participation in the study. 
 
Key inclusion criteria for this study are a diagnosis of POAG, PXG, or PG based on optic 
nerve neuropathy, an open angle, and elevated IOP of 23-39 mmHg in the absence of 
hypotensive medications.  In order to address the confounding effect of medications on 
the IOP-reducing ability of the devices, a "wash-out" of all glaucoma medications will be 
conducted, and a ‘diurnal’ methodology will be utilized to determine the subject’s 
eligibility.  The duration of wash-out will be determined by the specific medication(s) 
used. 
 
Upon successfully meeting the study inclusion/exclusion criteria, subjects will be 
scheduled for surgery.  Randomization will take place on the day of surgery just prior to 
treatment.  Randomization sequence will be based on pre-determined computer-generated 
lists. 
 
 
 
 

 
Ivantis, Inc. 
Protocol NCT02023242 
 
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Follow up will be continued for 2 years post-surgery, and will include assessments of the 
subject's IOP, ocular health, and visual acuity status.  Visits will be conducted at 1, 7, 30, 
180, 365, 540, and 730 days. 
 
In the event a study subject does not respond to device therapy, hypotensive glaucoma 
medications may be prescribed in order to reduce IOP to a safe level, as determined by 
the judgment of the attending physician.  Medications of the same type used prior to wash 
out will be re-started in this event.  Re-medication will not be considered an adverse 
event, but will be monitored.  Neither the Hydrus nor the iStent devices preclude the 
ability to later perform filtration surgery, in the event medications do not lower pressure 
adequately and more invasive therapy is required. 
 
3.0 
STUDY ENDPOINTS 
The primary effectiveness endpoint for this study is the proportion subjects with IOP 
≤19 mmHg and without the use of ocular hypotensive medications at 12 months, as 
measured by Goldmann tonometry. 
 
Secondary effectiveness endpoints include: 
• The proportion of subjects who are are not using ocular hypotensive medications at 
12 and 24 months, as measured by Goldmann tonometry 
• Mean medication use at 12 and 24 months 
• The proportion subjects with IOP ≤19 mmHg and without the use of ocular 
hypotensive medications at 24 months, as measured by Goldmann tonometry 
 
Safety endpoints include: 
• Frequency of loss in BCVA of 2 lines or more at 12 and 24 months, 
• Slit lamp and fundus examination findings at 12 and 24 months, 
• 
Frequency of complications and adverse events at all follow up periods.  
 
4.0 
STATISTICAL METHODS 
4.1 Study Hypothesis 
A 20% or greater reduction in the proportion of subjects requiring ocular hypotensive 
medications to reach a target IOP of 19 mmHg or less is a clinically significant treatment 
effect. 
 
4.2 Sample Size 
The study size is based on the primary endpoint. 
 
4.3 
Safety Analysis 
Safety data (adverse events, visual acuity measurements, perimetry, and ocular health 
findings based on slit lamp and fundus examinations) will be evaluated using descriptive 

 
Ivantis, Inc. 
Protocol NCT02023242 
 
Page 6 of 15 
statistics.  Frequency tabulations of safety outcomes will be performed for 1, 3, 6, 12, 18 
and 24-month follow up periods.  Safety analysis cohorts will be grouped by actual 
treatment.  The study is not designed to detect differences in safety outcomes. 
5.0 
STUDY POPULATION 
5.1 Inclusion Criteria 
Subjects who meet the following inclusion and exclusion criteria will be eligible for 
enrollment in this study.  Ocular criteria relates to the study eye only. 
 
• Male and female patients from 45 to 84 years of age. 
• A diagnosis of primary open angle glaucoma (POAG), pseudoexfoliative glaucoma 
(PXG), or pigmentary glaucoma (PG). 
• A phakic patient with BCVA of 20/30 or better. 
• A pseudophakic patient who has had cataract surgery >6 months from the time of 
study enrollment. 
• Subject is on ≥2 glaucoma medications at Screening. 
• Normal angle anatomy by gonioscopy with a Shaffer angle grade of ≥III in all four 
quadrants. 
• Optic nerve pathology characteristic of glaucoma described by at least one of the 
following: 
A) Thinning, narrowing, or notching of the optic disc rim. 
B) Diffuse optic disc cupping or asymmetric cupping. 
C) Diffuse or localized peripapillary retinal nerve fiber layer loss. 
• After glaucoma medication wash-out, a mean diurnal IOP of 23-39 mmHg by 
Goldmann applanation tonometry. 
• The subject can safely tolerate periodic wash out of glaucoma medications. 
• The subject is able to understand the requirements of the study and is willing to 
follow study instructions, provide written informed consent, and agree to comply with 
all study requirements. 
 
5.2 Exclusion Criteria 
Excluded from the study will be individuals with the following characteristics.  Unless 
specified otherwise, all ocular criteria refer to the study eye only. 
 
• Other secondary glaucoma (such as neovascular, uveitic, traumatic, steroid induced, 
lens induced, or glaucoma associated with increased episcleral venous pressure). 
• Closed angle forms of glaucoma. 
• Diagnosis of acute angle closure, congenital, malignant, or developmental glaucoma. 

 
Ivantis, Inc. 
Protocol NCT02023242 
 
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• Use of <2 or >4 ocular hypotensive medications.  (Note:  Combination medications 
count as 2 medications.) 
• Use of oral hypotensive medication(s) for glaucoma treatment of the fellow eye.  
• Previous incisional glaucoma surgery of any kind, including non-penetrating 
procedures such as deep sclerectomy or canaloplasty. 
• Significant ocular health risk by washout of medication.  
• Central corneal thickness >620 or <480 microns. 
• Proliferative diabetic retinopathy. 
• Previous surgery for retinal detachment. 
• Clinically significant corneal dystrophy. 
• Previous corneal surgery. 
• Previous refractive surgery. 
• Degenerative visual disorders such as wet age-related macular degeneration. 
• Clinically significant ocular pathology, other than glaucoma. 
• Clinically significant ocular inflammation or infection within thirty days prior to 
screening. 
• Uncontrolled systemic disease that in the opinion of the Investigator would put the 
subject’s health at risk and/or prevent the subject from completing all study visits. 
• 
Pregnant, nursing females or women of child-bearing potential who are not using an 
acceptable method of contraception.  
 
6.0 
STUDY PROCEDURES 
6.1 Subject Entry, Consent and Enrollment  
Participants will be recruited from the Investigators’ patient population or referrals.  
Patients that appear to be eligible will be approached for study participation and sign a 
patient informed consent (PIC) prior to the commencement of study related procedures. 
 
The investigator or designee will explain the study purpose, procedures, and subject 
responsibilities to the potential participant.  The subject should be given the opportunity 
to ask questions and allowed time to consider the information provided.  The subject’s 
willingness and ability to meet the follow-up requirements will be determined.  When it 
has been established that the subject is eligible for possible enrollment into the study, 
written informed consent will be obtained.  One copy of the informed consent form will 
be retained with the subject’s medical records, and one copy will be provided to the 
subject. 
 
Only one qualified eye per qualified subject may be randomized for treatment.  If both 
eyes qualify for enrollment, the eye with the worse best corrected visual acuity will be 
designated as the study eye. 
 

 
Ivantis, Inc. 
Protocol NCT02023242 
 
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6.2 Medication Wash Out 
After the subject has successfully completed the preoperative screening exam, he or she 
will be instructed to discontinue any ocular hypotensive medications in the designated 
treatment eye for the appropriate washout period, as listed in Table 1, prior to the 
Baseline Exam.  If upon washout, the subject experiences an IOP elevation to greater 
than 39 mmHg, or requires the reintroduction of hypotensive medications or a surgical 
intervention during the preoperative period, the subject will be treated appropriately and 
excluded from the study.  Any subject whose IOP does not fall within 23-39 mmHg will 
be exited from the study. 
 
TABLE 1 
 OCULAR HYPOTENSIVE MEDICATION WASHOUT PERIODS 
 
Carbonic Anhydrase Inhibitors  
  
Diamox® (Acetazolamide) – oral Rx  
14 days  
Neptazane® (Methazolamide) – oral Rx  
14 days  
Azopt® (Brinzolamide) 
14 days  
Trusopt® (Dorzolamide Hydrochloride) 
14 days  
 
Alpha Adrenergic Agonist  
  
Alphagan® (Brimonidine)  
14 days  
Iopidine® (Apraclonidine Hydrochloride)  
14 days  
Beta Blockers  
  
Betagan® (Levobunolol Hydrochloride) 
28 days  
Betoptic® (Betaxalol Hydrochloride)  
28 days 
OptiPranolol® (Metipranolol) 
28 days 
Timoptic/Betimol® (Timolol Maleate) 
28 days 
Prostaglandin Analogs  
  
Lumigan® (Bimatoprost) 
28 days 
Travatan® (Travoprost)  
28 days 
Xalatan® (Latanoprost) 
28 days 
Combined Medications 
 
Combigan® (Brimonidine Tartrate/Timolol 
Maleate) 
28 days 
Cosopt® (Dorzolamide Hydrochloride/ Timolol 
Maleate)  
28 days 
 
6.3 Goldmann Tonometry Procedure 
At the baseline, IOP will be assessed using diurnal Goldmann tonometry, after wash-out 
of hypotensive medications.  In this study, 3 IOP readings will be taken during daylight 
hours as follows:  
 
o Time 1:  9:00 AM (± 1 hour) 

 
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Protocol NCT02023242 
 
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o Time 2:  4 hours later (± 1 hour) than Time 1 
o Time 3:  4 hours later (± 1 hour) than Time 2 
 
A minimum of 2 IOP readings are to be taken at each time point.  If the first two IOP 
values at a time point are more than 2 mm apart, then a third reading should be taken. 
 
To calculate the mean diurnal IOP, the mean IOP value from each time point is used to 
calculate a grand average.  In the event one or more of the time points requires a third 
IOP reading, then the median IOP of that time point is used for the calculation of the 
mean diurnal IOP. 
 
IOP readings taken at screening and at all other follow up visits will be taken once during 
the visit at 9 AM ± 2 hours.  A minimum of 2 IOP readings are to be taken.  The mean of 
these readings will be used for the IOP value at that visit.  If the first two IOP readings 
are more than 2 mm apart, then a third reading should be taken. In this case the median of 
the 3 values will be used as the value for the visit. 
 
If the subject meets all criteria at the Baseline visit, he or she will be scheduled for 
surgery within 21 days of this visit.  On the day of surgery, the subject will be 
randomized to either the Hydrus group or iStent group.  Computer-generated 
randomization lists will be used, with separate randomization lists for each clinical site.  
The subject will not be informed of the randomization assignment and all study personnel 
will be instructed to maintain the “masking” of the treatment assignments. 
 
6.4 Surgical Procedure 
After the subject’s group is identified, the patient should receive one Hydrus or two 
iStents for the study eye.  The surgical procedure to implant either the Hydrus or iStent 
devices should be performed according to the manufacturer’s Instructions for Use.  
Surgery may be performed under either local or topical ophthalmic anesthesia. 
 
6.5 Perioperative Medication 
A topical antibiotic and a topical steroid will be administered after surgery.  The 
following dosing regimen is recommended: 
 
1. 
Moxifloxacin 0.5% (Vigamox® or equivalent), one drop four times per day 
commencing the day of the procedure and continued for approximately one week 
postoperatively. 
2. 
Prednisolone acetate 1.0% (Pred Forte® or equivalent), one drop four times per day 
for one week; followed by one drop three times per day for one week; followed by 
one drop two times per day for one week; followed by one drop once per day for 
one week, then discontinue. 
 

 
Ivantis, Inc. 
Protocol NCT02023242 
 
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Medication to treat transient post-operative spikes in IOP resulting from the use of 
viscoelastic and surgical manipulation may be required in the immediate postoperative 
period, as described below.  
 
6.6 Study Visits and Examination Schedule 
All subjects will participate in defined follow-up visits through 24 months.  A Case 
Report Form (CRF) shall be completed for each scheduled exam.  Unscheduled or 
interim visits should also be recorded using the appropriate CRF. 
 
The procedures associated with each study visit are outlined and summarized in 
Appendix 1 (Schedule of Events and Procedures). 
 
6.7 Unscheduled Visits 
Any visit to the clinical site, other than those specified in the protocol, at which the 
subject has a complaint regarding the study eye and/or treatment to the study eye is 
required or changed will be documented as an unscheduled visit.  The Investigator and/or 
qualified investigational staff will perform the procedures necessary to evaluate the study 
participant at these visits, and will record the visit in the subject’s chart and on an interim 
CRF.  No specific testing is required at interim visit. 
 
6.8 Postoperative Ocular Hypotensive Medications 
Since the implantation procedure involves the use of an ophthalmic viscoelastic agent and 
post-operative steroids, both of which are known to cause IOP elevation in some cases, 
use of glaucoma medications in the first month after surgery is expected.  The first line 
hypotensive medication in the immediate post-operative period (0-60 days) should be 
selected from the beta blocker class (if tolerated) as indicated in the table below.  In these 
cases, additional visits may be performed to assess IOP, and medications discontinued if 
the patient’s IOP allows. 
 
Long term medical therapy (defined as medications prescribed at or after the 90-day visit) 
may be implemented at the Investigator’s discretion in order to maintain a safe IOP. 
 
Patient medication usage (medication class, dose, frequency, and brand, if applicable) 
will be collected at the time of screening.  The medications should be assigned a rank 
order for the purpose of potential reintroduction.  If post-operative IOP increases to an 
unsafe level, ocular hypotensive medications should be reintroduced one at a time and 
following the order indicated at screening. 
 
If a medication prescribed in the immediate post-operative period does not match the 
class indicated on the screening list and is continued to the 3 month visit, then the subject 
should be switched to the pre-surgical medication class and dose if possible. 
 

 
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Protocol NCT02023242 
 
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Reintroduction of ocular hypotensive medication will be recorded in the appropriate Case 
Report Form, along with the clinical rationale for the decision to apply medications.  A 
record of all medications added, discontinued or changed will be documented on the 
appropriate Case Report Form. 
 
Because the use of ocular hypotensive medications to control IOP is a study endpoint, the 
CRF describing the introduction or discontinuation will be reviewed by the Medical 
Monitor for appropriateness and consistency across study groups.  The Medical Monitor 
will be masked to the identity of the treatment subject. 
 
6.9 Subject Disposition 
Subjects may be terminated (exited) from the study early due to: 
 
• Screening failure, 
• A threat to the subject’s health emerges in the course of following study procedures, 
• Inability to continue with the study, and 
• Voluntary withdrawal. 
 
Subjects who are terminated due to screening failure will not be followed beyond the date 
of screening failure.  For safety reasons, randomized subjects who are terminated should 
receive routine clinical follow up until the planned end of the study period.  CRF’s will 
not be completed for terminated subjects.  Terminated subjects will not be replaced.  
Notification of a subject’s early termination should be made immediately to the sponsor 
and documented on the appropriate CRF. 
 
Completed subjects are those subjects who have not been terminated from the study prior 
to completion of follow up. 
 
7.0 
ADVERSE EVENTS 
All ocular adverse events (AE) in the study eye must be reported on the adverse event 
CRF.  The Investigator must categorize each AE by degree of harm to the subject (mild, 
moderate, or severe), and the relationship to study device and implantation procedure (not 
related, possibly, probably, or definitely).  Since there are no aspects of the study that can 
affect both eyes, only serious adverse events observed in the fellow eye will be captured 
on the case report form throughout the course of the study. 
 
Ocular conditions or diseases that are chronic but stable and meet the inclusion and 
exclusion criteria should be recorded on the screening CRF under Ocular History.  
Changes in any chronic condition or disease that are consistent with natural disease 
progression are not considered AEs and will not be recorded on an AE CRF. 
 

 
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Protocol NCT02023242 
 
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7.1 Anticipated Adverse Events 
Anticipated AEs associated with glaucoma and/or cataract surgical procedures that might 
reasonably be expected to occur in this study are listed below.  These specific examples 
of anticipated AEs include, but are not limited to: 
 
7.2 Intraoperative Adverse Events 
• Hyphema obscuring the surgeon’s view  
• Choroidal hemorrhage or effusion 
• Significant iris injury or trauma 
• Corneal edema 
• Zonular dialysis 
 
7.3 Postoperative Adverse Events 
• Chronic pain in the study eye >3 months postoperative 
• Flat anterior chamber with lens/cornea touch or with iridocorneal apposition without 
lens/cornea touch >1 month postoperative 
• Best-corrected visual acuity loss of 2 lines (10 letters) or more on the ETDRS chart 
compared to baseline values, measured at or after 3 months postoperative 
• Hypotony (defined as IOP <6 mmHg) at or after 1 month postoperative 
• Maculopathy including hypotonic maculopathy 
• PAS with device obstruction 
• PAS without device obstruction 
• Device migration (dislodgement or movement) 
• Wound dehiscence (persistent aqueous leak or fistula formation) 
• Inflammation (defined as any inflammation requiring treatment with topical, sub-
Tenon’s or systemic anti-inflammatory medication) lasting longer than 1 month 
• Endophthalmitis 
• Persistent hyphema of >2 mm present >1 week postoperative 
• Corneal opacification 
• Corneal decompensation 
• Corneal edema persisting >1 month (mild to moderate corneal edema prior to 1 
month postoperative is not considered an adverse event) 
• Retinal complications (flap tears, retinal detachment, or proliferative 
vitreoretinopathy) 
• IOP spike (elevated mean IOP ≥10 mmHg above the qualifying baseline mean IOP 
more than 1 month postoperative) 
• Events resulting in an unplanned ocular surgical re-intervention (other than 
paracentesis to relieve pressure prior to 1 week postoperative) 
• Phthisis 
• Significant foreign body sensation at or after 3 months postoperative 
• A change in C/D ratio of ≥0.3 units on slit lamp biomicroscopic examination 

 
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Protocol NCT02023242 
 
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• A 2-point worsening to 4+ anterior chamber cells or flare at or after 3 months 
postoperative, not associated with a pre-existing condition 
• A 2-point worsening to severe on the slit lamp examination findings (other than cells 
and flare) at or after 3 months postoperative not associated with a pre-existing 
condition 
• A 2-point worsening of ocular symptoms to severe or very severe at or after 3 months 
postoperative not associated with a pre-existing condition 
 
7.4 Recording and Reporting Adverse Events 
To improve the quality and precision of acquired AE data, Investigators should observe the 
following guidelines: 
 
• Whenever possible, use recognized medical terms when recording AEs on the AE 
CRF.  Do not use colloquialisms and/or abbreviations. 
• For the purposes of reporting infection/inflammation, the following terms and 
definitions should be used: 
 
Iritis: 
Presence of inflammatory cells in the anterior chamber, with or 
without anterior vitreous inflammation.   
• 
The presence of aqueous flare alone will not be considered 
to constitute iritis. 
• 
For the purposes of this protocol, the term "iritis" will 
encompass both cases of iritis without anterior vitreous 
inflammation (iritis) and those with anterior vitreous 
inflammation (iridocyclitis). 
 
Iridocyclitis: 
Presence of inflammatory cells in both the aqueous and vitreous. 
 
Vitritis:   
Presence of active inflammation in the vitreous, as demonstrated 
by the presence of inflammatory cells (trace or greater) involving the 
mid-vitreous cavity. 
• 
The presence of inflammation involving only the anterior 
vitreous will not be considered to constitute vitritis because 
it may result from iridocyclitis (see above). 
• 
Active inflammation in the vitreous should be clinically 
differentiated from cellular debris from prior episodes of 
inflammation, hemorrhage, or other causes. 
• 
The presence of vitreous flare alone in the absence of active 
inflammatory cells will not be considered to constitute 
vitritis. 
Endophthalmitis: 
Diffuse intraocular inflammation predominantly involving the 
vitreous cavity but also involving the anterior chamber, implying a 
suspected underlying infectious cause, if known; record the 
diagnosis (i.e., disease or syndrome) rather than component signs 
and symptoms on AE pages of the CRF. 
 

 
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Protocol NCT02023242 
 
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7.5 Grading of AEs 
AEs are to be graded on a three-point scale (mild, moderate, severe) and reported in detail 
on the appropriate AE CRF.  The definitions are as follows: 
 
• Mild:  Discomfort noticed but no disruption of normal daily activity 
• Moderate:  Discomfort sufficient to reduce or affect normal daily activity 
• Severe:  Incapacitating with inability to work or perform normal daily activity, and any 
event resulting in death or requiring rehospitalization 
 
7.6 Adverse Events Requiring Expedited Reporting 
Investigators must report all SAEs to Ivantis within 48 hours of observing or learning of 
the event.  For initial SAE reports, investigators should record all case details that can be 
gathered within 48 hours on the adverse event CRF.  SAEs require expedited reporting to 
the Sponsor or designee regardless of relationship to the implanted devices. 
 
7.7 Unanticipated Adverse Device Effect 
An Unanticipated Adverse Device Effect (UADE) means any serious adverse effect (as 
defined above) on health or safety or any life-threatening problem or death caused by, or 
associated with a device, if that effect, problem, or death was not previously identified in 
nature, severity or degree of incidence in the investigational plan or application 
(including a supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare of subjects. 
 
Any UADE must be reported in writing to the Sponsor within 24 hours of knowledge of 
that event.  The Sponsor will be responsible for informing regulatory authorities and all 
other Medical Ethics Committees/IRBs and Investigators participating in the study of the 
UADE. 
 

 
 
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Protocol NCT02023242 
 
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APPENDIX 1: SCHEDULE OF EVENTS AND PROCEDURES 
PROCEDURE 
SCREENING1 
BASELINE 
SURGERY 
1 DAY 
POSTOP 
1 WEEK 
POSTOP 
1 
MONTH 
POSTOP 
3 
MONTHS 
POSTOP 
6 
MONTHS 
POSTOP 
121 
MONTHS 
POSTOP 
 
18 MONTH 
POST OP 
241  
MONTHS 
POSTOP 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Medical History and Physical  
X 
 
 
 
 
 
 
 
 
 
 
Ocular Medication Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BCVA - Snellen 
X 
 
 
 
 
 
 
 
 
 
 
Visual Acuity-Pinhole 
 
 
 
X 
 
 
 
 
 
 
 
BCVA - ETDRS 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Manifest Refraction 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Goldmann Tonometry 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Pachymetry  CCT 
X 
 
 
 
 
 
 
 
X 
 
X 
Gonioscopy (study eye)  
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Slit Lamp Exam 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Humphrey 24-2 SITA Standard 
X 
 
 
 
 
 
X 
 
X 
 
X 
Fundus Exam/C:D Ratio 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
Subject Symptoms Questionnaire 
 
 
 
 
 
 
 
 
 
 
X 
Adverse Event Assessment 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
1 At the Screening Visit, 12 Month and 24 Month postoperative visits, all assessments will be performed for both eyes.