Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7293   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Macular Edema Ranibizumab v. Intravitreal anti-inflammatory Therapy (MERIT) Trial

    Summary
    EudraCT number
    		 2017-003243-37
    Trial protocol
    		 GB  
    Global end of trial date
    02 Feb 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Oct 2023
    First version publication date
    06 Oct 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    140840
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02623426
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Johns Hopkins Bloomberg School of Public Health
    Sponsor organisation address
    415 N. Washington Street, Baltimore, United States, 21231
    Public contact
    Nancy Prusakowski, MERIT Coordinating Center Johns Hopkins Bloomberg School of Public Health, 001 4109558164, nprusak1@jhu.edu
    Scientific contact
    Janet Holbrook, PhD, MERIT Coordinating Center Johns Hopkins Bloomberg School of Public Health, 001 4432875791, jholbro1@jhu.edu
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    31 Jul 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Oct 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Feb 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Macular oedema is swelling of the retina at the back of the eye. It can cause vision loss and is a common complication in patients who have the eye condition uveitis (inflammation inside the eye). The MERIT Trial was designed to compare three treatments for uveitic macular oedema, to find out which intravitreal therapy offers the best balance of effectiveness and tolerability in eyes with controlled uveitis but persistent macular edema, specifically by comparing the relative efficacy and safety of intravitreal ranibizumab (Lucentis®) and intravitreal methotrexate to intravitreal dexamethasone implant (Ozurdex®) for the treatment of persistent uveitic macular oedema. The primary outcome will be the percent change in macular thickness from the baseline to the 12 week visit.
    Protection of trial subjects
    The injection procedures and treatment algorithm are consistent with standard clinical treatment, e.g., sterile technique, prophylactic pressure lowering medicine instilled prior to procedure. To minimize risks associated with increased ocular pressure post-injection, patients with uncontrolled ocular hypertension or glaucomatous changes are excluded from the trial. Pregnancy testing are required for women of childbearing potential before intravitreal injections of methotrexate or ranibizumab. Adverse events encountered will be managed by the best medical judgment of the treating physician. Confidentiality of patient data is maintained in accordance with legal regulations. Protected health information is kept in a secure place. Name, social security number, address, and other such personal data are kept solely at the clinical center where the patient receives her/his clinical care. Such information will not be transmitted to the Coordinating Center or to other study sites. A dataset limited so as to contain a minimal amount of protected health information–that required to make the data useful for accomplishing the purposes of the trial may be disclosed, as needed, to collaborating study sites, the NEI, and the FDA, as will be stated on a study privacy acknowledgment form signed by the participant at the time of enrollment.. This privacy acknowledgment will be designed to conform to specifications of HIPAA regulations, and any other relevant regulations, as approved by the local governing authorities invested with oversight of HIPAA regulations at each participating site. Clinically relevant information from the study may be placed in the patient's medical record. Release of protected health information to any other persons or organizations will require additional written consent of the patient affected, except as required by law.
    Background therapy
    		 -
    Evidence for comparator
    		 Recent pilot studies have shown intravitreal methotrexate (MTX) and intravitreal ranibizumab (Lucentis®, Genentech Inc., San Francisco, CA) to be promising treatments for uveitic ME, and intravitreal dexamethasone implant (Ozurdex®, Allergan, Irvine, CA) has recently been approved for uveitic ME in patients with non-infectious uveitis. In addition to being effective, intravitreal MTX and ranibizumab potentially may have less ocular side effects than corticosteroids, particularly less IOP elevation
    Actual start date of recruitment
    01 May 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 25
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    India: 27
    Country: Number of subjects enrolled
    United States: 127
    Worldwide total number of subjects
    194
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    132
    From 65 to 84 years
    62
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Screening details: 353 screened, 194 randomized Excluded Major reasons for exclusion were; central subfield macular thickness within the normal range for the OCT machine (38%) Patient preference (14%) Uveitis (9%) IOP issues (9%)

    Period 1
    Period 1 title
    Overall trial 12 weeks (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Reading center graders assessing primary outcome and visual acuity examiners masked to treatment

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dexamethasone intravitreal implant 0.7mg
    Arm description
    		 Dexamethasone intravitreal implant 0.7mg.Eligible eye(s) treated at study visit M01 (week 0). Retreatment required at study visit M03 (8 weeks) if re-treatment criteria met. Standard preparation as described for intravitreal injections. (Ozurdex®, Allergan, Irvine, CA)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Ozurdex (0.7 mg dexamethasone pellet)
    Investigational medicinal product code
    Other name
    intravitreal dexamethasone pellet, Ozurdex
    Pharmaceutical forms
    Emulsion for injection
    Routes of administration
    Intraocular use
    Dosage and administration details
    • Prepare eye for injection using the following sequence of steps: - Consider placing 2-3 drops of 5% povidone iodine in the lower fornix and/or using sterile cotton-tipped applicators soaked in 5% or 10% povidone iodine to swab the upper and lower eyelid margins and the upper and lower eyelashes (Optional) - Retract the eyelids and lashes away from the injection site and needle for the duration of the procedure (use of an eyelid speculum is optional) - Consider additional anesthesia with the application of one or two cotton-tipped applicators soaked in topical anesthetic over the intended injection site for at least 30 seconds. The use of lidocaine gel or other types of viscous anesthetic (e.g. TetraVisc™) is also permitted. A subconjunctival anesthetic can be used in specific circumstances in which the study ophthalmologist believes that topical anesthetic is not sufficient to minimize discomfort • Remove the lid speculum/unretract eyelid and lashes and avoid any excess pre

    Arm title
    		 Intravitreal methotrexate 400µg in 0.1mL
    Arm description
    		 Drug: Intravitreal Methotrexate 400 µg Intravitreal Methotrexate 400 µg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to the injection.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Intravitreal methotrexate 400 μg in 0.1 mL
    Investigational medicinal product code
    Other name
    Intravitreal methotrexate 400 μg in 0.1 mL
    Pharmaceutical forms
    Emulsion for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    Intravitreal methotrexate 400 μg in 0.1 mL Eligible eye(s) treated M01+ Retreatment required at M02, M03 if retreatment criteria met Retreatment permitted at M04 and later if retreatment criteria met Retreatment criteria: 1. Central subfield thickness greater than 1.1 times the upper limit of normal (330 μm for Zeiss and Topcon SD OCT and 352 μm for Heidelberg OCT) and/or cystoid space(s) within 1 mm central subfield. 1. IOP of <25 mm Hg (treatment with ≤3 IOP-lowering agents permitted), IOP criteria for initial injection of study treatment in eligible eye(s) is ≤21 mm Hg with ≤3 IOP-lowering agents

    Arm title
    		 Intravitreal ranibizumab 0.5mg in 0.05mL
    Arm description
    		 Intravitreal Ranibizumab 0.5 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to the injection. (Lucentis®, Genentech Inc., San Francisco, CA) Eligible eye(s) treated at study visit M01 (week 0). Retreatment required at study visit M03 (8 weeks) if re-treatment criteria met. Retreatment permitted at later time points if retreatment criteria met. Re-treatment criteria: Central subfield thickness greater than 1.1X upper limit of normal (330 μm for Zeiss and Topcon Spectral Domain (SD) Optical Coherence Tomography (OCT) and 352 μm for Heidelberg OCT) and/or cystoid space(s) within 1 mm central subfield. IOP of <25 mm Hg (treatment with ≤3 IOP-lowering agents permitted) Minimum time between treatments: minimum
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL
    Investigational medicinal product code
    Other name
    Lucentis
    Pharmaceutical forms
    Emulsion for emulsion for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    Intravitreal ranibizumab (Lucentis) 0.5 mg in 0.05 mL Eligible eye(s) treated M01+ Retreatment required at M02, M03 if retreatment criteria met Retreatment permitted at M04 and later if retreatment criteria met Retreatment criteria: 1) Central subfield thickness greater than 1.1 times the upper limit of normal (330 μm for Zeiss and Topcon SD OCT and 352 μm for Heidelberg OCT) and/or cystoid space(s) within 1 mm central subfield.

    Number of subjects in period 1
    		Dexamethasone intravitreal implant 0.7mg Intravitreal methotrexate 400µg in 0.1mL Intravitreal ranibizumab 0.5mg in 0.05mL
    Started
    65
    65
    64
    12 Week Primary outcome
    64
    63
    61
    Completed
    60
    59
    58
    Not completed
    5
    6
    6
         Lost to follow-up
    5
    6
    6

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Dexamethasone intravitreal implant 0.7mg
    Reporting group description
    		 Dexamethasone intravitreal implant 0.7mg.Eligible eye(s) treated at study visit M01 (week 0). Retreatment required at study visit M03 (8 weeks) if re-treatment criteria met. Standard preparation as described for intravitreal injections. (Ozurdex®, Allergan, Irvine, CA)

    Reporting group title
    Intravitreal methotrexate 400µg in 0.1mL
    Reporting group description
    		 Drug: Intravitreal Methotrexate 400 µg Intravitreal Methotrexate 400 µg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to the injection.

    Reporting group title
    Intravitreal ranibizumab 0.5mg in 0.05mL
    Reporting group description
    		 Intravitreal Ranibizumab 0.5 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to the injection. (Lucentis®, Genentech Inc., San Francisco, CA) Eligible eye(s) treated at study visit M01 (week 0). Retreatment required at study visit M03 (8 weeks) if re-treatment criteria met. Retreatment permitted at later time points if retreatment criteria met. Re-treatment criteria: Central subfield thickness greater than 1.1X upper limit of normal (330 μm for Zeiss and Topcon Spectral Domain (SD) Optical Coherence Tomography (OCT) and 352 μm for Heidelberg OCT) and/or cystoid space(s) within 1 mm central subfield. IOP of <25 mm Hg (treatment with ≤3 IOP-lowering agents permitted) Minimum time between treatments: minimum

    Reporting group values
    		 Dexamethasone intravitreal implant 0.7mg Intravitreal methotrexate 400µg in 0.1mL Intravitreal ranibizumab 0.5mg in 0.05mL Total
    Number of subjects
    		 65 65 64 194
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Age in years at baseline
    Units: years
        median (full range (min-max))
    		 59 (18 to 81) 59 (20 to 83) 57 (24 to 83) -
    Gender categorical
    Units: Subjects
        Female
    		 41 48 40 129
        Male
    		 24 17 24 65
    Race
    Units: Subjects
        Asian
    		 10 10 8 28
        Black
    		 16 22 13 51
        White
    		 38 28 41 107
        More than 1 race
    		 0 1 0 1
        Unknown race
    		 1 4 2 7
    Concomitant systemic medication
    Participant was on systemic medication for the treatment of macular edema or uveitis at baseline
    Units: Subjects
        Yes
    		 28 27 29 84
        No
    		 37 38 35 110
    Visual acuity
    Participants’ visual acuity was measured by certified examiners with best refractive correction in place. Participants were challenged with reading letters on lines of the standard ETDRS eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until no more meaningful readings could be made and were scored by how many letters could be correctly identified. More letters read is associated with higher visual acuity. (85 standard letters = 20/20 vision)
    Units: Standard letters
        median (full range (min-max))
    		 -
    Intraocular pression (IOP)
    Units: mm Hg
        median (full range (min-max))
    		 -
    Retinal thickness at the center subfield
    Central subfield thickness as measured by OCT at a fundus photograph reading center
    Units: um
        median (full range (min-max))
    		 -
    Subject analysis sets

    Subject analysis set title
    Macular edema eyes from Arm 1 (Ozurdex)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Eyes with macular edema at baseline for Arm 1

    Subject analysis set title
    Macular edema eyes in Arm 2 (Intravitreal Methotrexate)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Eyes with macular edema at baseline in Arm 2 (Intravitreal Methotrexate)

    Subject analysis set title
    Macular edema eyes from Arm 3 Intravitreal Ranibizumab
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Eyes with macular edema at baseline for Arm 3 Intravitreal Ranibizumab

    Subject analysis sets values
    		 Macular edema eyes from Arm 1 (Ozurdex) Macular edema eyes in Arm 2 (Intravitreal Methotrexate) Macular edema eyes from Arm 3 Intravitreal Ranibizumab
    Number of subjects
    77
    79
    69
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Age in years at baseline
    Units: years
        median (full range (min-max))
    Gender categorical
    Units: Subjects
        Female
        Male
    Race
    Units: Subjects
        Asian
        Black
        White
        More than 1 race
        Unknown race
    Concomitant systemic medication
    Participant was on systemic medication for the treatment of macular edema or uveitis at baseline
    Units: Subjects
        Yes
        No
    Visual acuity
    Participants’ visual acuity was measured by certified examiners with best refractive correction in place. Participants were challenged with reading letters on lines of the standard ETDRS eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until no more meaningful readings could be made and were scored by how many letters could be correctly identified. More letters read is associated with higher visual acuity. (85 standard letters = 20/20 vision)
    Units: Standard letters
        median (full range (min-max))
    68 (25 to 89)
    64 (6 to 85)
    67 (6 to 88)
    Intraocular pression (IOP)
    Units: mm Hg
        median (full range (min-max))
    15 (5 to 21)
    15 (5 to 23)
    14 (7 to 21)
    Retinal thickness at the center subfield
    Central subfield thickness as measured by OCT at a fundus photograph reading center
    Units: um
        median (full range (min-max))
    457 (241 to 1116)
    476 (276 to 991)
    401 (220 to 1091)

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Dexamethasone intravitreal implant 0.7mg
    Reporting group description
    		 Dexamethasone intravitreal implant 0.7mg.Eligible eye(s) treated at study visit M01 (week 0). Retreatment required at study visit M03 (8 weeks) if re-treatment criteria met. Standard preparation as described for intravitreal injections. (Ozurdex®, Allergan, Irvine, CA)

    Reporting group title
    Intravitreal methotrexate 400µg in 0.1mL
    Reporting group description
    		 Drug: Intravitreal Methotrexate 400 µg Intravitreal Methotrexate 400 µg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to the injection.

    Reporting group title
    Intravitreal ranibizumab 0.5mg in 0.05mL
    Reporting group description
    		 Intravitreal Ranibizumab 0.5 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to the injection. (Lucentis®, Genentech Inc., San Francisco, CA) Eligible eye(s) treated at study visit M01 (week 0). Retreatment required at study visit M03 (8 weeks) if re-treatment criteria met. Retreatment permitted at later time points if retreatment criteria met. Re-treatment criteria: Central subfield thickness greater than 1.1X upper limit of normal (330 μm for Zeiss and Topcon Spectral Domain (SD) Optical Coherence Tomography (OCT) and 352 μm for Heidelberg OCT) and/or cystoid space(s) within 1 mm central subfield. IOP of <25 mm Hg (treatment with ≤3 IOP-lowering agents permitted) Minimum time between treatments: minimum

    Subject analysis set title
    Macular edema eyes from Arm 1 (Ozurdex)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Eyes with macular edema at baseline for Arm 1

    Subject analysis set title
    Macular edema eyes in Arm 2 (Intravitreal Methotrexate)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Eyes with macular edema at baseline in Arm 2 (Intravitreal Methotrexate)

    Subject analysis set title
    Macular edema eyes from Arm 3 Intravitreal Ranibizumab
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Eyes with macular edema at baseline for Arm 3 Intravitreal Ranibizumab

    Primary: Proportion of Baseline Central Subfield Thickness Observed at 12 Weeks

    		 Close Top of page
    End point title
    		 Proportion of Baseline Central Subfield Thickness Observed at 12 Weeks
    End point description
    The primary outcome is the change in central subfield thickness from baseline to 12 weeks measured on a relative scale as the the proportion of the baseline central subfield thickness. Values less than 1 indicate a decrease in retinal thickness with lower values indicating greater decreases. Smaller values are better The assessment of OCT outcomes was performed by masked readers.
    End point type
    Primary
    End point timeframe
    The 12-week visit was chosen as the time to assess the primary outcome because the ranibizumab treatment arm specifies injections at baseline, 4 weeks and 8 weeks in all participants, and because the peak benefit for the dexamethasone pellet appears to be
    End point values
    		 Dexamethasone intravitreal implant 0.7mg Intravitreal methotrexate 400µg in 0.1mL Intravitreal ranibizumab 0.5mg in 0.05mL Macular edema eyes from Arm 1 (Ozurdex) Macular edema eyes in Arm 2 (Intravitreal Methotrexate) Macular edema eyes from Arm 3 Intravitreal Ranibizumab
    Number of subjects analysed
    0 [1]
    0 [2]
    0 [3]
    77
    79
    69
    Units: Proportion of baseline retinal thickness
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    0.65 (0.58 to 0.72)
    0.88 (0.81 to 0.96)
    0.79 (0.70 to 0.89)
    Notes
    [1] - analyzed eyes with ME
    [2] - Analyzed eyes with ME
    [3] - Analyzed eyes with ME
    Statistical analysis title
    		 Methotrexate compared to Ozurdex
    Statistical analysis description
    Mixed model was used to determine the treatment effect as the ratio of the proportions of baseline retinal thickness (Lucentis/Ozurdex) at 12 weeks. Values greater than 1 indicate less reduction in retinal thickness in the methotrexate treated group compared to Ozurdex
    Comparison groups
    Macular edema eyes from Arm 1 (Ozurdex) v Macular edema eyes in Arm 2 (Intravitreal Methotrexate)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Ratio of proportion of baseline
    Point estimate
    1.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.19
         upper limit
    		 1.56
    Notes
    [4] - Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection, Intravitreal Methotrexate 400 μg in 0.1 mL 0.9% Sodium Chloride Solution, Preservative-free
    Statistical analysis title
    		 Lucentis compared to Ozurdex
    Statistical analysis description
    Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection, Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL Comments The treatment effect is the ratio of the proportions of baseline retinal thickness (Lucentis/Ozurdex) at 12 weeks. Values greater than 1 indicate less reduction in retinal thickness in the Lucentis treated group compared to Ozurdex estimated by a mixed model
    Comparison groups
    Macular edema eyes from Arm 1 (Ozurdex) v Macular edema eyes from Arm 3 Intravitreal Ranibizumab
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.12 [5]
    Method
    		 Mixed models analysis
    Parameter type
    		 Ratio of the proportion of baseline
    Point estimate
    1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 1.43
    Notes
    [5] - Bonferroni correction was used to adjust for the co-primary hypotheses;a two-sided type I error rate of 0.05/2 = 0.025 was used to determine statistical significance for the two pairwise comparisons (Ozurdex vs Methotrexate and Ozurdex vs Lucentis)

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events over 24 weeks
    Adverse event reporting additional description
    Serious adverse events were reported via an expediated reporting system followed by medical safety review. Non-serious events collected in non-systemic means via an adverse event log that was completed at each visit and by systemic collection of information on ocular events of special interest on the follow up visit case reform forms.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Arm 1 Ozurdex (Demamethasone)
    Reporting group description
    		 -

    Reporting group title
    Arm 2 Intravitreal methotrexate
    Reporting group description
    		 Intravitreal methotrexate 400 μg in 0.1 mL Eligible eye(s) treated at week 0 Retreatment required at M02, M03 if retreatment criteria met Retreatment permitted at M04 and later if retreatment criteria met

    Reporting group title
    Arm 3 Intravitreal ranibizumab (Lucentis)
    Reporting group description
    		 Intravitreal ranibizumab (Lucentis) 0.5 mg in 0.05 mL Eligible eye(s) treated M01+ Retreatment required at M02, M03 if retreatment criteria met Retreatment permitted at M04 and later if retreatment criteria met

    Serious adverse events
    		 Arm 1 Ozurdex (Demamethasone) Arm 2 Intravitreal methotrexate Arm 3 Intravitreal ranibizumab (Lucentis)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 65 (15.38%)
    10 / 65 (15.38%)
    3 / 64 (4.69%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    breast caner
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    post procedure infection
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 65 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Vasovagal response
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 65 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Catheterization cardiac for hypertension
         subjects affected / exposed
    0 / 65 (0.00%)
    0 / 65 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    tachycardia
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Intraocular pressure decreased
         subjects affected / exposed
    2 / 65 (3.08%)
    0 / 65 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intraocular pressure increased
         subjects affected / exposed
    3 / 65 (4.62%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iridotomy
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    visual acuity decreased
         subjects affected / exposed
    0 / 65 (0.00%)
    5 / 65 (7.69%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    glaucoma
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 65 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Corneal oedema
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    2 / 65 (3.08%)
    0 / 65 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glaucoma surgery
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 65 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Rectal haemorrhage
         subjects affected / exposed
    0 / 65 (0.00%)
    0 / 65 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Arm 1 Ozurdex (Demamethasone) Arm 2 Intravitreal methotrexate Arm 3 Intravitreal ranibizumab (Lucentis)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    23 / 65 (35.38%)
    29 / 65 (44.62%)
    20 / 64 (31.25%)
    Investigations
    Intraocular pressure decreased
         subjects affected / exposed
    3 / 65 (4.62%)
    0 / 65 (0.00%)
    0 / 64 (0.00%)
         occurrences all number
    3
    0
    0
    Injury, poisoning and procedural complications
    Intraocular pressure fluctuation
    Additional description: Following treatment injection IOP was increased > than 30 mm Hg temporary
         subjects affected / exposed
    0 / 65 (0.00%)
    12 / 65 (18.46%)
    6 / 64 (9.38%)
         occurrences all number
    0
    24
    14
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 65 (0.00%)
    2 / 65 (3.08%)
    0 / 64 (0.00%)
         occurrences all number
    0
    2
    0
    Nervous system disorders
    headache
         subjects affected / exposed
    1 / 65 (1.54%)
    2 / 65 (3.08%)
    4 / 64 (6.25%)
         occurrences all number
    1
    4
    4
    Eye disorders
    Eye pain
         subjects affected / exposed
    8 / 65 (12.31%)
    5 / 65 (7.69%)
    5 / 64 (7.81%)
         occurrences all number
    13
    9
    7
    Ocular hypertension
         subjects affected / exposed
    2 / 65 (3.08%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences all number
    3
    2
    0
    surgery to control IOP
         subjects affected / exposed
    1 / 65 (1.54%)
    4 / 65 (6.15%)
    0 / 64 (0.00%)
         occurrences all number
    1
    5
    0
    Uveitis
         subjects affected / exposed
    2 / 65 (3.08%)
    2 / 65 (3.08%)
    2 / 64 (3.13%)
         occurrences all number
    2
    2
    2
    Vitreous haemorrhage
         subjects affected / exposed
    3 / 65 (4.62%)
    0 / 65 (0.00%)
    1 / 64 (1.56%)
         occurrences all number
    3
    0
    1
    Vitreous floaters
         subjects affected / exposed
    2 / 65 (3.08%)
    4 / 65 (6.15%)
    1 / 64 (1.56%)
         occurrences all number
    3
    5
    2
    Chalazion
         subjects affected / exposed
    1 / 65 (1.54%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences all number
    1
    1
    0
    Conjunctival haemorrhage
         subjects affected / exposed
    2 / 65 (3.08%)
    0 / 65 (0.00%)
    1 / 64 (1.56%)
         occurrences all number
    2
    0
    1
    Dry eye
         subjects affected / exposed
    2 / 65 (3.08%)
    1 / 65 (1.54%)
    2 / 64 (3.13%)
         occurrences all number
    3
    2
    2
    Eyelid oedema
         subjects affected / exposed
    2 / 65 (3.08%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences all number
    2
    1
    0
    Photopsia
         subjects affected / exposed
    4 / 65 (6.15%)
    2 / 65 (3.08%)
    0 / 64 (0.00%)
         occurrences all number
    6
    2
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 65 (1.54%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences all number
    1
    1
    0
    Nausea
         subjects affected / exposed
    0 / 65 (0.00%)
    2 / 65 (3.08%)
    1 / 64 (1.56%)
         occurrences all number
    0
    2
    1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    1 / 65 (1.54%)
    1 / 65 (1.54%)
    2 / 64 (3.13%)
         occurrences all number
    1
    1
    3
    Arthritis
         subjects affected / exposed
    1 / 65 (1.54%)
    1 / 65 (1.54%)
    0 / 64 (0.00%)
         occurrences all number
    1
    1
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 65 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    1
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    0 / 65 (0.00%)
    0 / 65 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    0
    2
    Pneumonia
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 65 (0.00%)
    1 / 64 (1.56%)
         occurrences all number
    1
    0
    1
    Sinusitis
         subjects affected / exposed
    2 / 65 (3.08%)
    1 / 65 (1.54%)
    1 / 64 (1.56%)
         occurrences all number
    2
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 65 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    1
    0
    2
    Urinary track infection
         subjects affected / exposed
    2 / 65 (3.08%)
    0 / 65 (0.00%)
    0 / 64 (0.00%)
         occurrences all number
    2
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    16 Mar 2020
    Enrollment was temporarily suspended due to the COVID-19 pandemic on 16 Mar 2020. Enrollment was permitted to resume on a clinic-by-clinic basis begining 23 Jul 2023.
    23 Jul 2020

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed May 08 03:26:54 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA