Clincosm LogoSign in Get a demo

Intraocular Pressure and Ocular Perfusion Pressure of Cosopt in Normal Tension Glaucoma

Sponsor
The Catholic University of Korea (Other)
Overall Status
Completed
CT.gov ID
NCT01175902
Collaborator
Seoul St. Mary's Hospital (Other)
44
Enrollment
1
Location
2
Arms
43
Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

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.
Condition or Disease Intervention/Treatment Phase
N/A

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)

Study Design

Study Type:
Interventional
Actual Enrollment :
44 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
To Prove the Non-inferiority of Cosopt Compared to Xalatan in the Aspects of Intraocular Pressure and Ocular Perfusion Pressure in Subjects With Normal Tension Glaucoma
Study Start Date :
Mar 1, 2011
Actual Primary Completion Date :
Oct 1, 2014
Actual Study Completion Date :
Oct 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm 1

Latanoprost first, then Dorzolamide/Timolol Patients first on Latanoprost eyedrops once a day, then on Dorzolamide/Timolol twice a day

Drug: dorzolamide/timolol
dorzolamide/timolol fixed combination eyedrop, 2 times a day
Other Names:
  • Cosopt

    • Drug: latanoprost
    compare with dorzolamide/timolol fixed combination eyedrop one time a day
    Other Names:
  • Xalatan

    		•
    Active Comparator: Arm 2

    Dorzolamide/Timolol first, then Latanoprost Patients first on Dorzolamide/Timolol eyedrops twice a day, then on Latanoprost eyedrops once a day

    Drug: dorzolamide/timolol
    dorzolamide/timolol fixed combination eyedrop, 2 times a day
    Other Names:
  • Cosopt

    • Drug: latanoprost
    compare with dorzolamide/timolol fixed combination eyedrop one time a day
    Other Names:
  • Xalatan

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Intraocular Pressure (IOP), Period 1 [4 weeks]

      IOP (mean IOP) after 4 weeks of treatment

    2. Intraocular Pressure (IOP), Period 2 [12 weeks]

      IOP (mean IOP) after treaemt from week 8 to week 12

    3. Blood Pressure (BP), Period 1 [4 weeks]

      systolic and diastolic BP at 4 weeks after use of eyedrops

    4. Blood Pressure (BP), Period 2 [12 weeks]

      systolic and diastolic BP measured after treaemt from week 8 to week 12

    Secondary Outcome Measures

    1. 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

    2. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    45 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Seoul St. Mary's hospital Seoul Korea, Republic of 137-070

    Sponsors and Collaborators

    • The Catholic University of Korea
    • Seoul St. Mary's Hospital

    Investigators

    • Principal Investigator: Chan Kee Park, M.D., PhD., The Catholic University of Korea

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Chan Kee Park, Seoul St. Mary's Hospital, The Catholic University of Korea
    ClinicalTrials.gov Identifier:
    NCT01175902
    Other Study ID Numbers:
    • cosopt-IOP/OPP
    First Posted:
    Aug 5, 2010
    Last Update Posted:
    Jan 8, 2015
    Last Verified:
    Dec 1, 2014
    Keywords provided by Chan Kee Park, Seoul St. Mary's Hospital, The Catholic University of Korea
    Normal tension glaucoma
    Additional relevant MeSH terms:
    Glaucoma
    Low Tension Glaucoma
    Timolol
    Dorzolamide
    Latanoprost

    Study Results

    Participant Flow

    Recruitment Details Seoul St. Mary's Hospital From April, 5th, 2011 to October, 16th, 2014
    Pre-assignment Detail 44 enrolled, 44 completed
    Arm/Group Title Latanoprost Dorzolamide/Timolol
    Arm/Group Description Patients on Latanoprost eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Patients on Dorzolamide/Timolol eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day
    Period Title: Overall Study
    STARTED 22 22
    COMPLETED 22 22
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Latanoprost Dorzolamide/Timolol Total
    Arm/Group Description Patients on Latanoprost eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Patients on Dorzolamide/Timolol eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Total of all reporting groups
    Overall Participants 22 22 44
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60.72
    (7.42)
    59.68
    (7.12)
    60.20
    (7.20)
    Sex: Female, Male (Count of Participants)
    Female
    15
    68.2%
    18
    81.8%
    33
    75%
    Male
    7
    31.8%
    4
    18.2%
    11
    25%
    Region of Enrollment (participants) [Number]
    Korea, Republic of
    22
    100%
    22
    100%
    44
    100%
    Spherical equivalent (diopters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [diopters]
    -0.74
    (1.95)
    -1.04
    (2.71)
    -0.89
    (2.34)
    Central corneal thickness (micrometers) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [micrometers]
    542.73
    (11.43)
    544.23
    (17.33)
    543.48
    (14.53)
    Mean deviation of visual field (decibels) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [decibels]
    -4.00
    (3.79)
    -2.92
    (2.96)
    -3.46
    (3.41)

    Outcome Measures

    1. Primary Outcome
    Title Intraocular Pressure (IOP), Period 1
    Description IOP (mean IOP) after 4 weeks of treatment
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Latanoprost, Period 1 Dorzolamide/Timolol, Period 1
    Arm/Group Description Patients on Latanoprost eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Patients on Dorzolamide/Timolol eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day
    Measure Participants 22 22
    IOP at 8am
    13.72
    (2.93)
    13.50
    (3.09)
    IOP at 10am
    13.27
    (2.37)
    13.36
    (2.75)
    IOP at 12pm
    13.54
    (2.30)
    12.63
    (2.98)
    IOP at 16pm
    13.77
    (2.50)
    13.77
    (2.61)
    IOP at 20pm
    13.36
    (1.89)
    13.63
    (2.46)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Latanoprost, Period 1, Dorzolamide/Timolol, Period 1
    Comments Comparison between two arms were made for IOP, systolic BP, diastolic BP and OPP at each time period.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments To prove the non-inferiority of Cosopt to Xalatan, the sample size calculation was based on the assumption that non-inferiority margin of trough IOP of 1.5mmHg. A sample size of n=21 patients per group, this study has 80% power (1-β=0.80) and α=0.05, crossover-designed analysis. In this study, the upper limit of the 95% CI is expected above the maximal acceptable clinically significant difference of 1.5 mmHg of IOP.
    Statistical Test of Hypothesis p-Value 0.05
    Comments Comparison between two arms were made for IOP, systolic BP, diastolic BP and OPP at each time period.
    Method t-test, 2 sided
    Comments Comparison between two arms were made for IOP, systolic BP, diastolic BP and OPP at each time period.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.9
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Comparison between two arms were made for IOP, systolic BP, diastolic BP and OPP at each time period.
    2. Primary Outcome
    Title Intraocular Pressure (IOP), Period 2
    Description IOP (mean IOP) after treaemt from week 8 to week 12
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Latanoprost, Period 2 Dorzolamide/Timolol, Period 2
    Arm/Group Description Patients on Latanoprost eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Patients on Dorzolamide/Timolol eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day
    Measure Participants 22 22
    IOP at 8am
    13.13
    (3.02)
    12.36
    (2.51)
    IOP at 10am
    12.81
    (3.21)
    12.36
    (2.55)
    IOP at 12pm
    12.54
    (3.05)
    12.72
    (2.45)
    IOP at 16pm
    12.81
    (3.24)
    13.04
    (2.41)
    IOP at 20pm
    13.40
    (2.36)
    13.13
    (2.07)
    3. Primary Outcome
    Title Blood Pressure (BP), Period 1
    Description systolic and diastolic BP at 4 weeks after use of eyedrops
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Latanoprost, Period 1 Dorzolamide/Timolol, Period 1
    Arm/Group Description Patients on Latanoprost eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Patients on Dorzolamide/Timolol eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day
    Measure Participants 22 22
    systolic BP at 8am
    121.82
    (16.25)
    122.82
    (17.90)
    systolic BP at 10am
    120.68
    (12.76)
    119.14
    (18.01)
    systolic BP at 12pm
    120.45
    (13.22)
    120.55
    (17.23)
    systolic BP at 16pm
    122.09
    (13.14)
    118.55
    (18.74)
    systolic BP at 20pm
    123.32
    (14.09)
    119.45
    (18.92)
    diastolic BP at 8am
    74.77
    (11.45)
    77.36
    (8.59)
    diastolic BP at 10am
    74.50
    (11.13)
    73.81
    (7.32)
    diastolic BP at 12pm
    74.22
    (9.71)
    73.18
    (7.53)
    diastolic BP at 16pm
    75.27
    (10.35)
    72.81
    (6.94)
    diastolic BP at 20pm
    75.95
    (11.78)
    74.13
    (7.52)
    4. Primary Outcome
    Title Blood Pressure (BP), Period 2
    Description systolic and diastolic BP measured after treaemt from week 8 to week 12
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Latanoprost, Period 2 Dorzolamide/Timolol, Period 2
    Arm/Group Description Patients on Latanoprost eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Patients on Dorzolamide/Timolol eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day
    Measure Participants 22 22
    systolic BP at 8am
    123.14
    (12.58)
    118.41
    (15.47)
    systolic BP at 10am
    123.59
    (12.06)
    117.95
    (12.73)
    systolic BP at 12pm
    122.41
    (11.89)
    119.05
    (13.999)
    systolic BP at 16pm
    124.50
    (12.78)
    118.45
    (14.90)
    systolic BP at 20pm
    123.23
    (14.88)
    119.82
    (13.34)
    diastolic BP at 8am
    76.45
    (7.71)
    73.72
    (9.67)
    diastolic BP at 10am
    74.86
    (8.40)
    72.50
    (7.70)
    diastolic BP at 12pm
    75.54
    (7.89)
    72.40
    (8.39)
    diastolic BP at 16pm
    73.45
    (7.50)
    71.36
    (8.78)
    diastolic BP at 20pm
    73.81
    (8.64)
    74.72
    (7.32)
    5. Secondary Outcome
    Title Ocular Perfusion Pressure (OPP), Period 1
    Description 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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Latanoprost, Period 1 Dorzolamide/Timolol, Period 1
    Arm/Group Description Patients on Latanoprost eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Patients on Dorzolamide/Timolol eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day
    Measure Participants 22 22
    OPP at 8am
    46.57
    (8.34)
    49.12
    (6.76)
    OPP at 10am
    46.65
    (6.81)
    46.95
    (6.06)
    OPP at 12pm
    46.21
    (6.64)
    48.17
    (5.51)
    OPP at 16pm
    46.81
    (7.14)
    45.44
    (5.98)
    OPP at 20pm
    47.79
    (7.34)
    46.73
    (6.73)
    6. Secondary Outcome
    Title OPP, Period 2
    Description 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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Latanoprost, Period 2 Dorzolamide/Timolol, Period 2
    Arm/Group Description Patients on Latanoprost eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Patients on Dorzolamide/Timolol eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day
    Measure Participants 22 22
    OPP at 8am
    48.36
    (6.00)
    46.71
    (7.34)
    OPP at 10am
    48.04
    (5.98)
    46.07
    (5.96)
    OPP at 12pm
    48.47
    (5.98)
    45.90
    (6.00)
    OPP at 16pm
    47.81
    (6.21)
    44.99
    (5.80)
    OPP at 20pm
    47.10
    (6.70)
    46.70
    (5.14)

    Adverse Events

    Time Frame During the 12 weeks study period
    Adverse Event Reporting Description
    Arm/Group Title Latanoprost Dorzolamide/Timolol
    Arm/Group Description Patients on Latanoprost eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day Patients on Dorzolamide/Timolol eyedrops dorzolamide/timolol fixed combination: Cosopt eyedrop, 2 times a day latanoprost: compare with Cosopt one time a day
    All Cause Mortality
    Latanoprost Dorzolamide/Timolol
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Latanoprost Dorzolamide/Timolol
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/44 (0%) 0/44 (0%)
    Other (Not Including Serious) Adverse Events
    Latanoprost Dorzolamide/Timolol
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/44 (0%) 0/44 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Chan Kee Park
    Organization Seoul St. Mary's Hospital
    Phone 82222586208
    Email ckpark@catholic.ac.kr
    Responsible Party:
    Chan Kee Park, Seoul St. Mary's Hospital, The Catholic University of Korea
    ClinicalTrials.gov Identifier:
    NCT01175902
    Other Study ID Numbers:
    • cosopt-IOP/OPP
    First Posted:
    Aug 5, 2010
    Last Update Posted:
    Jan 8, 2015
    Last Verified:
    Dec 1, 2014