Normal Tension Glaucoma
Conditions
Keywords
Normal tension glaucoma
Brief summary
To prove the non-inferiority of the fixed timolol-dorzolamide combination (Cosopt) compared to 0.005% latanoprost (Xalatan) in the aspects of intraocular pressure (IOP) and ocular perfusion pressure (OPP) in subjects with normal tension glaucoma (NTG) Clinical hypotheses. Primary hypothesis * Cosopt group is non-inferior to Xalatan group in diurnal IOP reduction. Secondary hypothesis * Cosopt group is non-inferior to Xalatan group in diurnal diastolic and systolic OPP.
Detailed description
Cosopt (dorzolamide/timolol fixed combination) has well known effect for IOP reduction in POAG and OHT.3-5 However, there is no study about the effect and safety of Cosopt in NTG, Cosopt is not used the first line drug in the management of NTG. In Korea, the prevalence of NTG is higher than western countries, the majority (about 80-90%) of open angle glaucoma patients have an IOP of 21 mmHg or less, so the study of NTG is important and searching of effective drug for the treatment of NTG is necessary. In this study, we would prove the non-inferiority of Cosopt compared to Xalatan,6 which is used as a first line drug in the management of NTG, in the aspects of IOP and OPP including diastolic OPP (DOPP). A prospective, interventional, randomized, crossover, single masked, single center study. Forty-four NTG patients were randomly allocated to one of two groups. Patients in group A were treated with Cosopt, lubricant, and Xalatan for 4 weeks each, whereas patients in group B were treated with Xalatan, lubricant, and Cosopt for 4 weeks each. Recruit NTG patients, who are not treated with the glaucoma medication recent 2 months. If treated, after washout period of 4 weeks, the patients can be included in the study. Baseline IOP, systolic and diastolic BP will be measured. (Day 1) After 4 weeks of treatment of Cosopt or Xalatan, all participants will be checked diurnal IOP, systolic and diastolic BP. IOP was measured by Goldmann applanation tonometry (mean of three consecutive readings) with the patient in a sitting position at the slit lamp. Every IOP will be measured by one masked glaucoma specialist who is unaware of the treatment assignments. After the IOP measurements, after a 5-minite rest, pulse rate and BP (systolic and diastolic) of radial artery were measured in the sitting position using a standard automated blood pressure cuff. During the period, all measuring instruments keep to be calibrated by the manufacturer's instruction. \- OPP was calculated according to the following formula: OPP=(1/3 systolic BP + 2/3 diastolic BP) x 2/3 -IOP, diastolic OPP (DOPP)=diastolic BP-IOP. During the 4 weeks washout period, subjects will use lubricants.(Week 8) In this crossover study, with the other eye drops, the same measurement will be performed. (Week 12)
Interventions
dorzolamide/timolol fixed combination eyedrop, 2 times a day
DRUGlatanoprost
compare with dorzolamide/timolol fixed combination eyedrop one time a day
Sponsors
Seoul St. Mary's Hospital
The Catholic University of Korea
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
The identification of NTG was based on reproducible glaucomatous visual field defects, corresponding to typical ONH changes. Unilateral or bilateral visual field loss (description as below) as determined by at least two consecutive automated static threshold perimetry tests. One eye is randomly selected in the cases where both eyes are treated. Inclusion criteria: 1. age ranging from 45 to 75 years 2. best-corrected visual acuity no worse than 20/30 Snellen equivalent 3. optic nerve head cupping (i.e., a vertical cup-to-disc ratio of more than 0.6) and/or notching of neuroretinal rim, and/or retinal nerve fiber defects characteristic of glaucoma 4. visual field loss (i.e., a localized defect with at least three adjacent nonedge points depressed \>5 dB from the normal value, and a nucleus of at least one point depressed 10 dB from the normal value) 5. repeated measurements of untreated IOP, which documented values less than 22 mmHg 6. central corneal thickness ranging from 540 to 560 microns 7. open-angle confirmed by gonioscopy
Exclusion criteria
1. active or chronic systemic diseases and/or concomitant assumption of any medication known to affect IOP, BP and/or HR 2. corneal abnormalities preventing reliable applanation tonometry 3. severe ocular trauma, ocular inflammation or infection, intraocular surgery or argon laser treatment or laser trabeculoplasty 4. myopic or other fundus changes preventing reliable optic disc evaluation, 5. visual field defects caused by nonglaucomatous disease 6. history of allergy to the ingredients of Cosopt or Xalatan eye drops
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressure (IOP), Period 1 | 4 weeks | IOP (mean IOP) after 4 weeks of treatment |
| Intraocular Pressure (IOP), Period 2 | 12 weeks | IOP (mean IOP) after treaemt from week 8 to week 12 |
| Blood Pressure (BP), Period 1 | 4 weeks | systolic and diastolic BP at 4 weeks after use of eyedrops |
| Blood Pressure (BP), Period 2 | 12 weeks | systolic and diastolic BP measured after treaemt from week 8 to week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Perfusion Pressure (OPP), Period 1 | 4 weeks | OPP was calculated according to the following formula: OPP=(1/3 systolic BP + 2/3 diastolic BP) x 2/3 -IOP, diastolic OPP (DOPP)=diastolic BP-IOP |
| OPP, Period 2 | 12 weeks | OPP was calculated according to the following formula: OPP=(1/3 systolic BP + 2/3 diastolic BP) x 2/3 -IOP, diastolic OPP (DOPP)=diastolic BP-IOP OPP after treaemt from week 8 to week 12 |
Countries
South Korea
Participant flow
Recruitment details
Seoul St. Mary's Hospital From April, 5th, 2011 to October, 16th, 2014
Pre-assignment details
44 enrolled, 44 completed
Participants by arm
| Arm | Count |
|---|---|
| Latanoprost Patients on Latanoprost eyedrops
dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day
latanoprost: compare with Cosopt one time a day | 22 |
| Dorzolamide/Timolol Patients on Dorzolamide/Timolol eyedrops
dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day
latanoprost: compare with Cosopt one time a day | 22 |
| Total | 44 |
Baseline characteristics
| Characteristic | Dorzolamide/Timolol | Total | Latanoprost |
|---|---|---|---|
| Age, Continuous | 59.68 years STANDARD_DEVIATION 7.12 | 60.20 years STANDARD_DEVIATION 7.2 | 60.72 years STANDARD_DEVIATION 7.42 |
| Central corneal thickness | 544.23 micrometers STANDARD_DEVIATION 17.33 | 543.48 micrometers STANDARD_DEVIATION 14.53 | 542.73 micrometers STANDARD_DEVIATION 11.43 |
| Mean deviation of visual field | -2.92 decibels STANDARD_DEVIATION 2.96 | -3.46 decibels STANDARD_DEVIATION 3.41 | -4.00 decibels STANDARD_DEVIATION 3.79 |
| Region of Enrollment Korea, Republic of | 22 participants | 44 participants | 22 participants |
| Sex: Female, Male Female | 18 Participants | 33 Participants | 15 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 7 Participants |
| Spherical equivalent | -1.04 diopters STANDARD_DEVIATION 2.71 | -0.89 diopters STANDARD_DEVIATION 2.34 | -0.74 diopters STANDARD_DEVIATION 1.95 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 44 | 0 / 44 |
| serious Total, serious adverse events | 0 / 44 | 0 / 44 |
Outcome results
Primary
Blood Pressure (BP), Period 1
systolic and diastolic BP at 4 weeks after use of eyedrops
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 8am | 121.82 mmHg | Standard Deviation 16.25 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 10am | 120.68 mmHg | Standard Deviation 12.76 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 12pm | 120.45 mmHg | Standard Deviation 13.22 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 16pm | 122.09 mmHg | Standard Deviation 13.14 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 20pm | 123.32 mmHg | Standard Deviation 14.09 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 8am | 74.77 mmHg | Standard Deviation 11.45 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 10am | 74.50 mmHg | Standard Deviation 11.13 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 12pm | 74.22 mmHg | Standard Deviation 9.71 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 16pm | 75.27 mmHg | Standard Deviation 10.35 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 20pm | 75.95 mmHg | Standard Deviation 11.78 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 12pm | 73.18 mmHg | Standard Deviation 7.53 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 8am | 122.82 mmHg | Standard Deviation 17.9 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 8am | 77.36 mmHg | Standard Deviation 8.59 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 10am | 119.14 mmHg | Standard Deviation 18.01 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 20pm | 74.13 mmHg | Standard Deviation 7.52 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 12pm | 120.55 mmHg | Standard Deviation 17.23 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 10am | 73.81 mmHg | Standard Deviation 7.32 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 16pm | 118.55 mmHg | Standard Deviation 18.74 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | diastolic BP at 16pm | 72.81 mmHg | Standard Deviation 6.94 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 1 | systolic BP at 20pm | 119.45 mmHg | Standard Deviation 18.92 |
Primary
Blood Pressure (BP), Period 2
systolic and diastolic BP measured after treaemt from week 8 to week 12
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 8am | 123.14 mmHg | Standard Deviation 12.58 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 10am | 123.59 mmHg | Standard Deviation 12.06 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 12pm | 122.41 mmHg | Standard Deviation 11.89 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 16pm | 124.50 mmHg | Standard Deviation 12.78 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 20pm | 123.23 mmHg | Standard Deviation 14.88 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 8am | 76.45 mmHg | Standard Deviation 7.71 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 10am | 74.86 mmHg | Standard Deviation 8.4 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 12pm | 75.54 mmHg | Standard Deviation 7.89 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 16pm | 73.45 mmHg | Standard Deviation 7.5 |
| Latanoprost, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 20pm | 73.81 mmHg | Standard Deviation 8.64 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 12pm | 72.40 mmHg | Standard Deviation 8.39 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 8am | 118.41 mmHg | Standard Deviation 15.47 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 8am | 73.72 mmHg | Standard Deviation 9.67 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 10am | 117.95 mmHg | Standard Deviation 12.73 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 20pm | 74.72 mmHg | Standard Deviation 7.32 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 12pm | 119.05 mmHg | Standard Deviation 13.999 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 10am | 72.50 mmHg | Standard Deviation 7.7 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 16pm | 118.45 mmHg | Standard Deviation 14.9 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | diastolic BP at 16pm | 71.36 mmHg | Standard Deviation 8.78 |
| Dorzolamide/Timolol, Period 1 | Blood Pressure (BP), Period 2 | systolic BP at 20pm | 119.82 mmHg | Standard Deviation 13.34 |
Primary
Intraocular Pressure (IOP), Period 1
IOP (mean IOP) after 4 weeks of treatment
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 10am | 13.27 mmHg | Standard Deviation 2.37 |
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 16pm | 13.77 mmHg | Standard Deviation 2.5 |
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 12pm | 13.54 mmHg | Standard Deviation 2.3 |
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 20pm | 13.36 mmHg | Standard Deviation 1.89 |
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 8am | 13.72 mmHg | Standard Deviation 2.93 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 20pm | 13.63 mmHg | Standard Deviation 2.46 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 8am | 13.50 mmHg | Standard Deviation 3.09 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 10am | 13.36 mmHg | Standard Deviation 2.75 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 12pm | 12.63 mmHg | Standard Deviation 2.98 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 1 | IOP at 16pm | 13.77 mmHg | Standard Deviation 2.61 |
Comparison: Comparison between two arms were made for IOP, systolic BP, diastolic BP and OPP at each time period.p-value: 0.05t-test, 2 sided
Primary
Intraocular Pressure (IOP), Period 2
IOP (mean IOP) after treaemt from week 8 to week 12
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 10am | 12.81 mmHg | Standard Deviation 3.21 |
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 16pm | 12.81 mmHg | Standard Deviation 3.24 |
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 12pm | 12.54 mmHg | Standard Deviation 3.05 |
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 20pm | 13.40 mmHg | Standard Deviation 2.36 |
| Latanoprost, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 8am | 13.13 mmHg | Standard Deviation 3.02 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 20pm | 13.13 mmHg | Standard Deviation 2.07 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 8am | 12.36 mmHg | Standard Deviation 2.51 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 10am | 12.36 mmHg | Standard Deviation 2.55 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 12pm | 12.72 mmHg | Standard Deviation 2.45 |
| Dorzolamide/Timolol, Period 1 | Intraocular Pressure (IOP), Period 2 | IOP at 16pm | 13.04 mmHg | Standard Deviation 2.41 |
Secondary
Ocular Perfusion Pressure (OPP), Period 1
OPP was calculated according to the following formula: OPP=(1/3 systolic BP + 2/3 diastolic BP) x 2/3 -IOP, diastolic OPP (DOPP)=diastolic BP-IOP
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Latanoprost, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 10am | 46.65 mmHg | Standard Deviation 6.81 |
| Latanoprost, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 16pm | 46.81 mmHg | Standard Deviation 7.14 |
| Latanoprost, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 12pm | 46.21 mmHg | Standard Deviation 6.64 |
| Latanoprost, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 20pm | 47.79 mmHg | Standard Deviation 7.34 |
| Latanoprost, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 8am | 46.57 mmHg | Standard Deviation 8.34 |
| Dorzolamide/Timolol, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 20pm | 46.73 mmHg | Standard Deviation 6.73 |
| Dorzolamide/Timolol, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 8am | 49.12 mmHg | Standard Deviation 6.76 |
| Dorzolamide/Timolol, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 10am | 46.95 mmHg | Standard Deviation 6.06 |
| Dorzolamide/Timolol, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 12pm | 48.17 mmHg | Standard Deviation 5.51 |
| Dorzolamide/Timolol, Period 1 | Ocular Perfusion Pressure (OPP), Period 1 | OPP at 16pm | 45.44 mmHg | Standard Deviation 5.98 |
Secondary
OPP, Period 2
OPP was calculated according to the following formula: OPP=(1/3 systolic BP + 2/3 diastolic BP) x 2/3 -IOP, diastolic OPP (DOPP)=diastolic BP-IOP OPP after treaemt from week 8 to week 12
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Latanoprost, Period 1 | OPP, Period 2 | OPP at 10am | 48.04 mmHg | Standard Deviation 5.98 |
| Latanoprost, Period 1 | OPP, Period 2 | OPP at 16pm | 47.81 mmHg | Standard Deviation 6.21 |
| Latanoprost, Period 1 | OPP, Period 2 | OPP at 12pm | 48.47 mmHg | Standard Deviation 5.98 |
| Latanoprost, Period 1 | OPP, Period 2 | OPP at 20pm | 47.10 mmHg | Standard Deviation 6.7 |
| Latanoprost, Period 1 | OPP, Period 2 | OPP at 8am | 48.36 mmHg | Standard Deviation 6 |
| Dorzolamide/Timolol, Period 1 | OPP, Period 2 | OPP at 20pm | 46.70 mmHg | Standard Deviation 5.14 |
| Dorzolamide/Timolol, Period 1 | OPP, Period 2 | OPP at 8am | 46.71 mmHg | Standard Deviation 7.34 |
| Dorzolamide/Timolol, Period 1 | OPP, Period 2 | OPP at 10am | 46.07 mmHg | Standard Deviation 5.96 |
| Dorzolamide/Timolol, Period 1 | OPP, Period 2 | OPP at 12pm | 45.90 mmHg | Standard Deviation 6 |
| Dorzolamide/Timolol, Period 1 | OPP, Period 2 | OPP at 16pm | 44.99 mmHg | Standard Deviation 5.8 |