Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04981886 |
| Other study ID # |
HMS1311 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
August 2021 |
| Est. completion date |
August 2022 |
Study information
| Verified date |
August 2021 |
| Source |
Salus University |
| Contact |
Edgar U Ekure, OD, MS |
| Phone |
3157532421 |
| Email |
exe0003[@]salus.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Glaucoma is the second leading cause of blindness and the first leading cause of irreversible
vision loss worldwide. The intraocular pressure (IOP) is the only modifiable risk factor for
all the spectrum of glaucoma. Reducing IOP in glaucoma increases the likelihood of preventing
progression of the disease and preserving the quality of life of the patient. Although
prostaglandin analogs (PGAs) and prostamides (PMs) are de facto first-line treatment options
for managing glaucoma, it is a common clinical experience to see their treatment effects
plateau to a level beyond which no clinically significant IOP reduction is likely. It is also
common to find minimal IOP treatment effects in the following conditions: patients with
normal tension glaucoma (NTG), patients with thicker central corneal thickness (CCT), and
patients with higher levels of corneal hysteresis (CH). CH is a possible proxy for the
ability of the scleral tissue around the optic nerve to dissipate energy away from the optic
nerve fibers. Netarsudil, a rho-kinase inhibitor was recently approved by the FDA for the
treatment of glaucoma and ocular hypertension. There is a paucity of research on the efficacy
of netarsudil in patients with NTG, thicker CCT, and higher levels of CH. This study aims to
investigate the above issues by evaluating the efficacy of netarsudil and bimatoprost in
subjects with NTG, thicker corneas, and higher levels of CH.
Hypotheses
- Netarsudil will have non-inferior efficacy compared to Bimatoprost in treating NTG.
- Corneal thickness and corneal hysteresis will reduce the efficacy of netarsudil similar
to bimatoprost in NTG.
- Netarsudil will change corneal thickness and corneal hysteresis similar to bimatoprost
in NTG.
Description:
CHARACTERISTICS OF THE SUBJECT POPULATION
1. Target Accrual. The target number of participants we aim to recruit is one hundred and
fifteen (115). Participants will be recruited from the patient base of Roberts Eyecare
Associates in Vestal, New York, and from referrals from other practices.
2. Gender of the Subjects. There will be no gender restriction in the study.
3. Age Range of Adult Subjects. The age range of participants is 21 to 89 years. This age
range is based on the Collaborative Normal Tension Glaucoma Study (CNTGS).
4. Age Range of Pediatric Subjects. Not applicable.
5. Racial and Ethnic Origin. There will be no restriction based on race or ethnicity.
6. Vulnerable Subjects. It is not anticipated that the study will include vulnerable
subjects like pregnant persons, breastfeeding persons, persons considering becoming
pregnant, children, prisoners, individuals with impaired decision-making capacity, Salus
employees and/or students. However, if any subject meeting the inclusion criteria is
determined to be a vulnerable subject as defined above, they will be excluded for
participation.
METHODS AND PROCEDURES
1. Patient History
The initial examination will include a comprehensive patient history that will include
the following:
- date of birth
- race/ethnicity
- ocular and general medical history
- list of the medications
- family ocular and general medical history
- allergy history
- social history, including history of smoking, alcohol, and recreational drug use.
2. Procedures at first visit
1. Ocular Response Analyzer (ORA: Reichert ophthalmic instrument, Buffalo, NY, USA):
This test will be used to automatically measure corneal hysteresis (CH), corneal
corrected intraocular pressure (IOPcc), and Goldman equivalent intraocular pressure
(IOPg). At least 5 readings will be taken and the highest 3 wave score readings
above 6.5 will be averaged to get measurements for CH, CRF, IOPcc, and IOPg.
2. Humphrey's Threshold Visual field test:
The 24-2 threshold Humphrey's visual field analyzer with the sita standard
algorithm will be used to determine the status of visual field for all
participants. Three visual field tests will be conducted to ensure reliability and
repeatability. Visual field test results with > 33% fixation losses, > 33% false
positive, or 33% false negative errors will be excluded.
3. Spectral-Domain Optical Coherence Tomography (SD-OCT) Test The SD-OCT is a medical
imaging technique for acquiring high resolution images of the retina and optic
nerve. This instrument emits a broad bandwidth, near infrared light from a
super-luminescent diode onto the retina. Reflected light rays from the retina are
analyzed by interferometry and Fourier-transformed into high resolution
quasi-histologic images of the retina and optic nerve.
4. Slit-Lamp Biomicroscopy Slit-lamp examination of the eyes of all participants will
be performed. The slit-lamp utilizes a beam of light and a pair of microscopes to
aid in the detailed examination of the ocular tissues from the external parts of
the eye, the adnexa, to the posterior aspect including the optic nerve and retina.
5. Goldman Applanation Tonometry (GAT) Goldman Applanation Tonometry (GAT). Goldman
applanation tonometry is a routine test for measuring intraocular pressure (IOP).
It is a contact tonometer, therefore, 1 drop of the anesthetic, proparacaine will
be used to numb the eye. Two GAT measurements will be taken. If the readings differ
by more than 2 mmHg, a third measurement will be carried out. The principal
investigator will be masked to the readings. A second optometrist (study
optometrist 1) will record the IOPs and the average of two readings with a
difference ≤ 2 mmHg will be taken.
6. Dynamic contour tonometry (DCT) The DCT is a contact tonometer with a concave tip
which has an electronic sensor. The radius of curvature of the tip is 10.5 mm. An
electronic pressure sensor is integrated into the center of the contacting tip
surface. When the tip of the DCT contacts the corneal surface, it conforms to the
curvature of the tip. This allows the electronic sensor measure IOP independent of
corneal properties. The measured IOP is displayed on the instrument. Two readings
with the best quality scores will be averaged and recorded by a study optometrist
1. The principal investigator will be masked to the IOP readings. Intraocular
pressure (IOP) measured by most tonometers typically have errors associated with
corneal parameters like CCT, CH, and corneal curvature. The DCT will help overcome
the influences of these corneal parameters on IOP measurement.
7. Gonioscopy Gonioscopy is a procedure used to examine the anterior chamber angles of
the eye. The procedure is carried out by means of a contact lens called the Gonio
lens. Gonioscopy will be performed immediately after GAT. A drop of Proparacaine 1%
may be added as needed to prolong local anesthetic effects. Gonioscopy will be used
to rule out other forms of glaucoma like Angle closure glaucoma, Inflammatory
glaucoma, pigmentary, and pseudo-exfoliation glaucoma.
8. Dilated Fundus Examination (DFE) Pupillary dilation will be done with the
instillation of 1% tropicamide in both eyes. Detailed examination of the anterior
chamber, lens, vitreous, optic nerve, macular, retinal up to the periphery of the
retina, will be performed. The purpose of the DFE is to establish the baseline
ocular status and to rule out ocular diseases that may confound the findings of the
study.
9. Systemic blood pressure (BP) The BP of all participants will be measured using an
automatic blood pressure measuring device. The ocular perfusion pressure (OPP) will
be calculated by taking the difference of the systolic blood pressure (SBP) and the
IOP (OPP = SBP - IOP). Arterial pulse amplitude (APA) will be calculated by taking
the difference of the SBP and diastolic BP (DBP) (APA = SBP - DBP).
3. Adherence to treatment
In order to monitor adherence to treatment, participants will be given a calendar log to
write in the number of drops instilled, the date and time of instillation.
4. Follow-up visit schedule:
Follow-up visits after the onset of treatment will be 2 weeks, 6 weeks, and 3 months
after the onset of treatment. Please see below for what data will be collected for these
follow-up visits.
5. Procedures to be carried out at follow-up visits The following procedures will be
carried out at all the follow-up visits outlined above.
- Assessment of participants' logbook to ensure adherence to treatment. Level of
adherence will be quantified based on the number of drops, and days missed.
- A traditional paper survey will be used to assess possible adverse events.
- Slit lamp examination to elicit any signs of adverse events and signs of disease
progression.
- GAT to measure IOPs.
- ORA to measure CH, CRF, IOPcc, and IOPg.
- DCT to measure IOP and OPA.
6. Statistical analysis and sample size calculation
a. Intent-to-treat analyses (ITT) This protocol shall follow the ITT analyses. All
participant data shall be analyzed in the original treatment assignment even if they
discontinue study mid-way or change treatment assignments.
Two sample size calculations were performed. The first was for non-inferiority between
netarsudil and bimatoprost. The second was for a sub-group analysis of the effect of
corneal thickness and CH on the efficacy of both drugs. Since the sub-group analysis
yielded the highest sample size, details were presented here. Subjects were classified
into 2 CCT sub-groups (thin corneas: ≤ 540 µm, thick: > 540 µm) based on the
classification scheme used by Johnson et al (2008). The change in IOP in those with thin
corneas treated with netarsudil will be compared to those with thin corneas treated with
Lumigan. The same comparison will be made for those with thick corneas. An effect size
of 2.4 mmHg was used based on derivation from a SD of 3.0. Assuming a power = 80%, and
an alpha = 0.05, the calculated sample size was 26. Since we have 2 groups (thin and
thick corneas) with 2 treatment arms (netarsudil and bimatoprost), the total calculated
sample size for the 4 groups was 104. A 10% increase was added to the calculated sample
size to account for attrition. The total sample size needed to detect the effects of all
the aims of research is therefore 115.
7. Data Storage and Confidentiality.
1. Data Storage:
Hard copies of data including OCT, Visual field, Ocular Response Analyzer printouts
will be collected and kept in the individual participant record folder. All
individual record folders will be stored in secure, locked metal cabinets. All
digital data will be stored in a password-protected computer. All data will be made
available to the Salus University Institutional Review Board (IRB) upon request.
The analysis of the data for presentation will only show participants ID and age.
2. Data management:
All data shall be kept in the Essential document folder, and pertinent data from all
individual participant forms shall be stored in a safe, password-protected computer. All
individual participant data will further be aggregated in a spreadsheet, de-identified,
and made ready for analysis.
8. RISK/BENEFIT ASSESSMENT
1. Potential Risks. The risks involved in the intervention are the same risks patients
are normally exposed to in clinical practice with the treatment of NTG.
Expected risks with the use of netarsudil and bimatoprost include conjunctival
hyperemia, redness, stinging or burning sensation, and dry eyes. Changes in iris
pigmentation could result from the use of bimatoprost.
2. Risk Classification. The overall risk classification for the study is minimal and
not greater than what is normally experienced in clinical practice. This definition
of minimal risk is in accordance with the Health and Human Services/Food and Drugs
Administration (HHS/FDA) Regulations which classifies minimal risk as "the
probability and magnitude of harm or discomfort anticipated in the research are not
greater in and of themselves than those ordinarily encountered in daily life or
during the performance of routine physical or psychological examinations or tests."
3. Protection Against Risks. The safety of treatment will be assessed at every visit
with a patient interview and a thorough eye examination. The study does not have a
Data Safety Monitoring Board (DSMB). However, all adverse events will be promptly
reported to the Salus University IRB.
4. Potential Benefits to the Subject. The study protocol involves the treatment of NTG
with standard FDA-approved medical treatment for glaucoma. This is necessary to
prevent progression of the disease.
5. Potential Benefits to Society. This project may provide evidence for a more
efficacious treatment of NTG. Secondly, it may provide evidence for the adequate
control of IOP in NTG patients with thicker corneas, and or greater CH.
9. Therapeutic Alternatives. Many therapeutic alternatives exist for the study
participants. These alternatives include, latanoprost, travoprost, latanoprostene bunod,
combigan, timolol, dorzolamide, etc. The therapeutic agents used in this study, and
other agents will also be available to any participant who chooses not to continue in
the study but wishes to continue with the treatment.
10. Risk/Benefit Relationship. netarsudil and bimatoprost have been shown to be efficacious
anti-glaucoma agents. These agents are already being widely used in clinical practice.
The risks posed by these agents do not exceed that of alternatives. The benefits include
reduction of IOPs, and reduction in the risk of progression of glaucoma. The benefits of
this study therefore outweigh the potential risks.
11. Financial Compensation for Participation. Subjects who complete the 3 months of
follow-up visit will receive a $20 Target gift card.
12. SUBJECT IDENTIFICATION, RECRUITMENT, AND CONSENT Method of Subject Identification and
Recruitment. Potential participants will be recruited from patients attending regular
clinic at Roberts Eyecare Associates in Vestal New York. Flyers will be designed and
handed to other eyecare practices announcing the clinical trial. All potential
participants will undergo a complete eye examination to determine their eligibility for
inclusion. All those meeting the inclusion criteria will be informed of the study. Those
who agree to participate will be given an informed consent form to read. Only those who
agree to participate after reading and demonstrating understanding of the entailments of
the study and has duly signed, will be recruited.
13. Competing Protocols. After searching the National Institute of Health (NIH) registered
clinical trials, at this time, there seem to be no competing protocol with substantial
eligibility criteria as this study.
14. Subject Competency. All subjects are expected to be competent to give informed consent.
If a subject who meets the eligibility criteria is not competent to give informed
consent, an informed consent shall be sought from the participant's legal healthcare
proxy.
15. Process of Informed Consent. Informed consent will be sought from all subjects to be
recruited for the study. The inform consent will include a detailed explanation of the
purpose of the study in a language that is accessible to a fifth-grade student. It will
also include an explanation of the risks and benefits of the study interventions.
Participants in the study will also be advised of expected adverse events they may
experience. They will be informed of their rights to discontinue participation in the
study at any time. A statement reassuring participants that treatment for glaucoma will
continue even if they choose to leave the study, will also be included in the informed
consent form. Only subjects who have received instructions on the study and have signed
the informed consent form will be recruited for the study. The informed consent form
will be filled at least two weeks before the commencement of the study.
The consent form shall contain no statement penalizing subjects for non-participation,
or statements absolving the study researchers of legal responsibilities in cases of
severe adverse events or misconduct.
16. Subject/Representative Comprehension. All subjects or their legal representatives will
be asked if they understand the content of the informed consent. If they confirm
understanding they will be encouraged to explain, to the best of their understanding,
what the study entails, and the content of the formed consent form. This will include,
purpose of the study, procedures, potential risks, potential benefits, alternatives, and
any other information pertinent to informed consent.
17. Information Purposely Withheld. No information will be purposely withheld from the
subject.
18. Documentation of Consent/Assent. Edgar U Ekure (OD, MS, FAAO) shall be responsible for
documenting the obtainment of informed consent from the subject.
