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   43871   clinical trials with a EudraCT protocol, of which   7290   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:
    An international, multicenter, randomized, blinded-assessor, parallel-group clinical study comparing eye drops of combined LEvofloxAcin + DExamethasone foR 7 days followed by dexamethasone alone for an additional 7 days vs. tobramycin + dexamethasone for 14 days for the prevention and treatment of inflammation and prevention of infection associated with cataract surgery in adults – LEADER 7.

    Summary
    EudraCT number
    		 2018-000286-36
    Trial protocol
    		 ES   IT  
    Global end of trial date
    19 Dec 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Oct 2020
    First version publication date
    17 Oct 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    LEVODESA_04-2017
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    NTC SRL
    Sponsor organisation address
    Via dei Gracchi, 35, Milano, Italy, 20146
    Public contact
    Dr. Federico Bertocchi, NTC SRL, 0039 0243850436, federico.bertocchi@ntcpharma.com
    Scientific contact
    Dr. Federico Bertocchi, NTC SRL, 0039 0243850436, federico.bertocchi@ntcpharma.com
    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
    22 Mar 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Dec 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the non-inferiority of combined levofloxacin + dexamethasone eye drops for 7 days followed by dexamethasone eye drops alone for an additional 7 days vs. standard treatment tobramycin + dexamethasone eye drops for 14 days in the prevention and treatment of postoperative ocular inflammation and prevention of infection.
    Protection of trial subjects
    The trial will be conducted in accordance with International Conference on Harmonisation Good Clinical Practice (ICH GCP) and all applicable laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Sep 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 652
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Russian Federation: 140
    Worldwide total number of subjects
    808
    EEA total number of subjects
    668
    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)
    145
    From 65 to 84 years
    628
    85 years and over
    35

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Study period: • Date of first enrolment: 03.09.2018 • Date study finalized (LPLV): 19.12.2018 Study centers: • 42 centers in Italy • 4 centers in Spain • 4 centers in Russia • 1 center in Germany

    Pre-assignment
    Screening details
    		 Planned sample size n.800; randomized patients n.808; screened patients n.863 In the section "population of trial subjects", the population of randomized patients (n. 808) has been inserted instead of the population of enrolled patients (n. 863)

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Assessor [1]

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone
    Arm description
    		 Levofloxacin + dexamethasone ophthalmic solution containing levofloxacin hemihydrate 5.12 mg/ml, corresponding to levofloxacin 5 mg/ml, and dexamethasone sodium phosphate 1.32 mg/ml, corresponding to dexamethasone 1 mg/ml (L-DSP), followed by Dexamethasone 1 mg/ml ophthalmic suspension (Maxidex). Dose and regimen: Levofloxacin + dexamethasone sodium phosphate eye drops for 7 days, 1 x 30 μl drop - 4 times a day, followed by dexamethasone eye drops (Maxidex) for an additional 7 days, 1 drop - 4 times a day.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Levofloxacin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Eye drops
    Routes of administration
    Conjunctival use
    Dosage and administration details
    Levofloxacin + dexamethasone sodium phosphate eye drops for 7 days, 1 x 30 μl drop - 4 times a day, followed by dexamethasone eye drops (Maxidex) for an additional 7 days, 1 drop - 4 times a day.

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Eye drops
    Routes of administration
    Conjunctival use
    Dosage and administration details
    Levofloxacin + dexamethasone sodium phosphate eye drops for 7 days, 1 x 30 μl drop - 4 times a day, followed by dexamethasone eye drops (Maxidex) for an additional 7 days, 1 drop - 4 times a day.

    Arm title
    		 Tobramycin + Dexamethasone
    Arm description
    		 Tobramycin 3 mg/ml + dexamethasone 1 mg/ml eye drops suspension (Tobradex) Dose and regimen: 1 drop - 4 times a day for 14 days
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tobramycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Eye drops
    Routes of administration
    Conjunctival use
    Dosage and administration details
    Tobramycin 3 mg/ml + dexamethasone 1 mg/ml eye drops suspension (Tobradex) 1 drop - 4 times a day for 14 days

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Eye drops
    Routes of administration
    Conjunctival use
    Dosage and administration details
    Tobramycin 3 mg/ml + dexamethasone 1 mg/ml eye drops suspension (Tobradex) 1 drop - 4 times a day for 14 days

    Notes
    [1] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: This is a randomized, assessor-blinded, parallel-group study
    Number of subjects in period 1
    		Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Started
    403
    405
    Received at Least One Treatment
    395
    393
    Completed
    388
    388
    Not completed
    15
    17
         Physician decision
    1
    2
         Consent withdrawn by subject
    7
    8
         Other
    -
    2
         Adverse event
    5
    3
         Lost to follow-up
    1
    1
         Protocol deviation
    1
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Levofloxacin + Dexamethasone Followed by Dexamethasone
    Reporting group description
    		 Levofloxacin + dexamethasone ophthalmic solution containing levofloxacin hemihydrate 5.12 mg/ml, corresponding to levofloxacin 5 mg/ml, and dexamethasone sodium phosphate 1.32 mg/ml, corresponding to dexamethasone 1 mg/ml (L-DSP), followed by Dexamethasone 1 mg/ml ophthalmic suspension (Maxidex). Dose and regimen: Levofloxacin + dexamethasone sodium phosphate eye drops for 7 days, 1 x 30 μl drop - 4 times a day, followed by dexamethasone eye drops (Maxidex) for an additional 7 days, 1 drop - 4 times a day.

    Reporting group title
    Tobramycin + Dexamethasone
    Reporting group description
    		 Tobramycin 3 mg/ml + dexamethasone 1 mg/ml eye drops suspension (Tobradex) Dose and regimen: 1 drop - 4 times a day for 14 days

    Reporting group values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone Total
    Number of subjects
    		 403 405 808
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 72 73 145
        From 65-84 years
    		 312 316 628
        85 years and over
    		 19 16 35
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 72.20 ± 8.59 71.96 ± 8.67 -
    Gender categorical
    Units: Subjects
        Female
    		 234 248 482
        Male
    		 169 157 326
    Race
    Units: Subjects
        White
    		 401 403 804
        Asian
    		 1 1 2
        American Indian or Alaska Native
    		 1 0 1
        Native Hawaiian or other Pacific Islander
    		 0 1 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Levofloxacin + Dexamethasone Followed by Dexamethasone
    Reporting group description
    		 Levofloxacin + dexamethasone ophthalmic solution containing levofloxacin hemihydrate 5.12 mg/ml, corresponding to levofloxacin 5 mg/ml, and dexamethasone sodium phosphate 1.32 mg/ml, corresponding to dexamethasone 1 mg/ml (L-DSP), followed by Dexamethasone 1 mg/ml ophthalmic suspension (Maxidex). Dose and regimen: Levofloxacin + dexamethasone sodium phosphate eye drops for 7 days, 1 x 30 μl drop - 4 times a day, followed by dexamethasone eye drops (Maxidex) for an additional 7 days, 1 drop - 4 times a day.

    Reporting group title
    Tobramycin + Dexamethasone
    Reporting group description
    		 Tobramycin 3 mg/ml + dexamethasone 1 mg/ml eye drops suspension (Tobradex) Dose and regimen: 1 drop - 4 times a day for 14 days

    Primary: Proportion of Participants Without Signs of Anterior Chamber Inflammation

    		 Close Top of page
    End point title
    		 Proportion of Participants Without Signs of Anterior Chamber Inflammation
    End point description
    The proportion of participants without signs of anterior chamber inflammation (sum of cells and flare score = 0). The following non-inferiority hypotheses has been tested: H0 : πT – πS ≤ - Δ; H1 : πT – πS > - Δ. Where πT and πS are the proportion of participants without signs of anterior chamber inflammation in the test and standard treatments, respectively, and the non-inferiority margin is Δ = 10%. The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Primary
    End point timeframe
    Day 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: Count of Participants
        Number of participants without signs
    376
    373
        Number of participants with signs
    19
    20
    Statistical analysis title
    		 Non-inferiority test
    Statistical analysis description
    Difference between proportions of patients without signs of anterior chamber inflammation (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.0028
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0275
         upper limit
    		 0.0331

    Secondary: Incidence of endophthalmitis

    		 Close Top of page
    End point title
    		 Incidence of endophthalmitis
    End point description
    The incidence of endophthalmitis was assessed and reported. Diagnosis of endophthalmitis is based on clinical evaluation of signs and symptoms (such as swollen eyelids, ocular pain, conjunctival hyperemia, decreased visual acuity, opaque vitreous) through slit lamp examination, and microbiological tests on conjunctival or corneal swabs. The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set). This outcome was not analyzed by applying the Last Observation Carried Forward (LOCF) method to impute missing values if at least one post-baseline value was available.
    End point type
    Secondary
    End point timeframe
    Day 4, 8, 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: Count of Participants
        Visit 3 - Day 4: patients evaluable at the Visit
    393
    393
        Visit 3 - Day 4: no diagnosis of endophthalmitis
    393
    393
        Visit 4 - Day 8: patients evaluable at the Visit
    391
    393
        Visit 4 - Day 8: no diagnosis of endophthalmitis
    391
    393
        Visit 5 – Day 15: patients evaluable at the Visit
    389
    391
        Visit 5 – Day 15: no diagnosis of endophthalmitis
    389
    391
    No statistical analyses for this end point

    Secondary: Proportion of Participants Without Signs of Anterior Ocular Chamber Inflammation

    		 Close Top of page
    End point title
    		 Proportion of Participants Without Signs of Anterior Ocular Chamber Inflammation
    End point description
    Proportion of participants without signs of anterior chamber inflammation (sum of cells and flare score = 0). The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Secondary
    End point timeframe
    Day 4 and 8
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: Count of Participants
        Visit 3 - Day 4: N. of participants without signs
    289
    302
        Visit 3 - Day 4: N. of participants with signs
    106
    91
        Visit 4 - Day 8: N. of participants without signs
    338
    341
        Visit 4 - Day 8: N. of participants with signs
    57
    52
    Statistical analysis title
    		 Superiority Test (Visit 3 – Day 4)
    Statistical analysis description
    Difference between proportions of patients without signs of anterior chamber inflammation (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Tobramycin + Dexamethasone v Levofloxacin + Dexamethasone Followed by Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.0368
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0972
         upper limit
    		 0.0236
    Statistical analysis title
    		 Superiority Test (Visit 4 – Day 8)
    Statistical analysis description
    Difference between proportions of patients without signs of anterior chamber inflammation (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0602
         upper limit
    		 0.0362

    Secondary: Proportion of patients with presence/absence of conjunctival hyperemia

    		 Close Top of page
    End point title
    		 Proportion of patients with presence/absence of conjunctival hyperemia
    End point description
    Conjunctival hyperemia was evaluated with slit lamp and results provided as a score as follows: 0 = absence of inflammation, 1 = mild inflammation (some vessels injected), 2 = moderate inflammation (diffuse injection of vessels, but individual vessels are still discernable) 3 = severe inflammation (intense injection of vessels, individual vessels not easily discernable). The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Secondary
    End point timeframe
    Day 4, 8, 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: Count of Participants
        Visit 3 - Day 4: Score=0
    337
    323
        Visit 3 - Day 4: Score>0
    58
    70
        Visit 4 - Day 8: Score=0
    348
    358
        Visit 4 - Day 8: Score>0
    47
    35
        Visit 5 - Day 15: Score=0
    371
    375
        Visit 5 - Day 15: Score>0
    24
    18
    Statistical analysis title
    		 Superiority Test (Visit 3 – Day 4)
    Statistical analysis description
    Difference between proportions of patients without conjunctival hyperemia (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.0313
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0202
         upper limit
    		 0.0828
    Statistical analysis title
    		 Superiority Test (Visit 4 – Day 8)
    Statistical analysis description
    Difference between proportions of patients without conjunctival hyperemia (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.0299
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0725
         upper limit
    		 0.0126
    Statistical analysis title
    		 Superiority Test (Visit 5 – Day 15)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.015
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0463
         upper limit
    		 0.0164

    Secondary: Total ocular symptoms score (TOSS)

    		 Close Top of page
    End point title
    		 Total ocular symptoms score (TOSS)
    End point description
    The TOSS is a patient-reported evaluation in the TOSS Questionnaire of 3 ocular symptoms: itching/burning, hyperemia of conjunctiva and tearing. A score was given in the presence of symptoms: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Secondary
    End point timeframe
    Day 4, 8, 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: score on a scale
    arithmetic mean (standard deviation)
        Visit 3 - Day 4
    0.29 ± 0.63
    0.37 ± 0.73
        Visit 4 - Day 8
    0.28 ± 0.67
    0.26 ± 0.62
        Visit 5 - Day 15
    0.17 ± 0.49
    0.17 ± 0.59
    No statistical analyses for this end point

    Secondary: Ocular Pain/Discomfort: 4-point Scale

    		 Close Top of page
    End point title
    		 Ocular Pain/Discomfort: 4-point Scale
    End point description
    Overall ocular pain and discomfort was evaluated by the subject on a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe). The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Secondary
    End point timeframe
    Day 4, 8, 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: Count of Participants
        Day 4: Presence/absence of ocular pain: Score=0
    360
    361
        Day 4: Presence/absence of ocular pain: Score>0
    35
    32
        Day 8: Presence/absence of ocular pain: Score=0
    366
    366
        Day 8: Presence/absence of ocular pain: Score>0
    29
    27
        Day 15: Presence/absence of ocular pain: Score=0
    377
    373
        Day 15: Presence/absence of ocular pain: Score>0
    18
    20
    Statistical analysis title
    		 Superiority Test (Visit 3 – Day 4)
    Statistical analysis description
    Difference between proportions of patients with an ocular pain and discomfort score of zero (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.0072
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0461
         upper limit
    		 0.0318
    Statistical analysis title
    		 Superiority Test (Visit 4 – Day 8)
    Statistical analysis description
    Difference between proportions of patients with an ocular pain and discomfort score of zero (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.0047
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0406
         upper limit
    		 0.0312
    Statistical analysis title
    		 Superiority Test (Visit 5 – Day 15)
    Statistical analysis description
    Difference between proportions of patients with an ocular pain and discomfort score of zero (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.0053
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0246
         upper limit
    		 0.0352

    Secondary: Use of Rescue Therapy

    		 Close Top of page
    End point title
    		 Use of Rescue Therapy
    End point description
    All rescue therapy used following cataract surgery is to be reported at all visits. The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Secondary
    End point timeframe
    During all the treatment until day 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: Count of Participants
        Patients with rescue therapy
    3
    1
        Patients with no rescue therapy
    392
    392
    Statistical analysis title
    		 Superiority Test
    Statistical analysis description
    Difference between proportions of patients with any rescue therapy (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.0051
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0049
         upper limit
    		 0.015

    Secondary: Intraocular Pressure (IOP)

    		 Close Top of page
    End point title
    		 Intraocular Pressure (IOP)
    End point description
    IOP is measured using a tonometer. IOP is measured as mmHg; normal intraocular pressures average between 12-22 mm Hg. The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Secondary
    End point timeframe
    At day 0 (screening) and at day 4, 8, 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: mmHg
    arithmetic mean (standard deviation)
        Visit 1 - Screening
    15.16 ± 2.48
    15.12 ± 2.41
        Visit 3 - Day 4
    14.26 ± 2.73
    14.49 ± 2.81
        Visit 4 - Day 8
    14.29 ± 2.51
    14.45 ± 3.03
        Visit 5 - Day 15
    14.45 ± 2.65
    14.37 ± 2.47
    No statistical analyses for this end point

    Other pre-specified: Visual Acuity

    		 Close Top of page
    End point title
    		 Visual Acuity
    End point description
    Visual acuity was assessed as per local clinical practice, i.e. with the Snellen (feet) or the ETDRS (meter) chart. Visual acuity was then analysed using decimal unit. Decimal score is the decimal expression of the Snellen (feet) or the ETDRS (meter) charts in which the numerator indicates the distance from the chart and the denominator indicates the size of the smallest line that can be read. Decimal values were provided directly from the investigator or computed as a result of the Snellen or ETDRS fraction. Generally decimal values from 0.01 to 0.10 indicate severe vision loss; decimal values from 0.125 to 0.25 indicate moderate vision loss; decimal values from 0.32 to 0.63 indicate mild vision loss; decimal values from 0.8 to 1.6 indicate normal vision. Lower decimal values correspond to a reduced visual acuity and worst outcomes, while higher decimal values indicate an improved visual acuity and better outcomes. The analysis population is represented by all randomized patients
    End point type
    Other pre-specified
    End point timeframe
    At day 0 (screening) and at day 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: decimal score
    arithmetic mean (standard deviation)
        Visit 1 - Screening
    0.41 ± 0.23
    0.41 ± 0.26
        Visit 5 - Day 15
    0.88 ± 0.19
    0.89 ± 0.17
    No statistical analyses for this end point

    Other pre-specified: Adverse Events

    		 Close Top of page
    End point title
    		 Adverse Events
    End point description
    Adverse events were described according to System Organ Classes (SOC) and Preferred Terms (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) and were presented by treatment group. The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Other pre-specified
    End point timeframe
    From baseline to the end of the treatment, corresponding to 15 days and 30 days (for SAEs) after the last day of study participation.
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: Count of Participants
        Patients with TEAEs
    56
    51
        Patients with serious TEAEs
    4
    2
        Patients with TEAEs suspected to be study related
    26
    26
        Patients with TEAEs leading to discontinuation
    4
    3
        Patients with fatal TEAEs
    1
    0
        Patients with severe TEAEs
    3
    0
    No statistical analyses for this end point

    Other pre-specified: Global Evaluation of Local Tolerability

    		 Close Top of page
    End point title
    		 Global Evaluation of Local Tolerability
    End point description
    Global evaluation was evaluated on a 4-point scale: 0 = no intolerability, 1 = mild intolerability, 2 = moderate intolerability, 3 = maximum intolerability The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Other pre-specified
    End point timeframe
    Day 4, 8, 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: score on a scale
    arithmetic mean (standard deviation)
        Visit 3 - Day 4
    0.03 ± 0.21
    0.01 ± 0.09
        Visit 4 - Day 8
    0.01 ± 0.11
    0.03 ± 0.19
        Visit 5 - Day 15
    0.02 ± 0.15
    0.02 ± 0.13
    Statistical analysis title
    		 Superiority Test - Global evaluation - Visit 3
    Statistical analysis description
    Difference between mean value of global evaluation (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.0178
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.005
         upper limit
    		 0.0406
    Statistical analysis title
    		 Superiority Test - Global evaluation - Visit 4
    Statistical analysis description
    Difference between mean value of global evaluation (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.0127
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0343
         upper limit
    		 0.009
    Statistical analysis title
    		 Superiority Test - Global evaluation - Visit 5
    Statistical analysis description
    Difference between mean value of global evaluation (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.0001
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0199
         upper limit
    		 0.0201

    Other pre-specified: Burning, Stinging, Blurred Vision

    		 Close Top of page
    End point title
    		 Burning, Stinging, Blurred Vision
    End point description
    Burning, stinging, blurred vision were evaluated on a 4-point scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Other pre-specified
    End point timeframe
    Day 4, 8, 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: score on a scale
    arithmetic mean (standard deviation)
        Burning: visit 3 - day 4
    0.08 ± 0.27
    0.09 ± 0.29
        Burning: visit 4 - day 8
    0.06 ± 0.24
    0.11 ± 0.35
        Burning: visit 5 - day 15
    0.07 ± 0.29
    0.07 ± 0.27
        Stinging: visit 3 - day 4
    0.05 ± 0.23
    0.04 ± 0.20
        Stinging: visit 4 - day 8
    0.07 ± 0.29
    0.07 ± 0.26
        Stinging: visit 5 - day 15
    0.06 ± 0.26
    0.04 ± 0.20
        Blurred vision: visit 3 - day 4
    0.06 ± 0.27
    0.05 ± 0.23
        Blurred vision: visit 4 - day 8
    0.06 ± 0.25
    0.04 ± 0.22
        Blurred vision: visit 5 - day 15
    0.03 ± 0.20
    0.01 ± 0.11
    Statistical analysis title
    		 Superiority Test - Burning - Visit 3
    Statistical analysis description
    Difference between mean value of burning (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.0153
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0541
         upper limit
    		 0.0236
    Statistical analysis title
    		 Superiority Test - Burning - Visit 4
    Statistical analysis description
    Difference between mean value of burning (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.0582
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1003
         upper limit
    		 -0.0161
    Statistical analysis title
    		 Superiority Test - Burning - Visit 5
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.0029
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0364
         upper limit
    		 0.0422
    Statistical analysis title
    		 Superiority Test - Stinging - Visit 3
    Statistical analysis description
    Difference between mean value of stinging (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.0076
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0229
         upper limit
    		 0.0382
    Statistical analysis title
    		 Superiority Test - Stinging - Visit 4
    Statistical analysis description
    Difference between mean value of stinging (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.0003
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.038
         upper limit
    		 0.0387
    Statistical analysis title
    		 Superiority Test - Stinging - Visit 5
    Statistical analysis description
    Difference between mean value of stinging (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.0182
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0141
         upper limit
    		 0.0505
    Statistical analysis title
    		 Superiority Test - Blurred vision - Visit 3
    Statistical analysis description
    Difference between mean value of blurred vision (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.0153
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.02
         upper limit
    		 0.0505
    Statistical analysis title
    		 Superiority Test - Blurred vision - Visit 4
    Statistical analysis description
    Difference between mean value of blurred vision (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.0181
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0148
         upper limit
    		 0.051
    Statistical analysis title
    		 Superiority Test - Blurred vision - Visit 5
    Statistical analysis description
    Difference between mean value of blurred vision (Levofloxacin+Dexamethasone vs. Tobramycin+Dexamethasone)
    Comparison groups
    Levofloxacin + Dexamethasone Followed by Dexamethasone v Tobramycin + Dexamethasone
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.0181
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0048
         upper limit
    		 0.041

    Other pre-specified: Assessment of Patient Diary (Compliance)

    		 Close Top of page
    End point title
    		 Assessment of Patient Diary (Compliance)
    End point description
    Treatment compliance is derived from the number of instillations each day during the study treatment exposure The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
    End point type
    Other pre-specified
    End point timeframe
    Day 15
    End point values
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Number of subjects analysed
    395
    393
    Units: Count of Participants
        No missed dose
    332
    332
        1 missed dose per day or 3 missed doses per week
    59
    57
        > 1 missed dose per day or > 3 missed doses per we
    4
    4
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From baseline to the end of the treatment, corresponding to 15 days and 30 days (for SAEs) after the last day of study participation.
    Adverse event reporting additional description
    It is not possible to attribute Adverse Events to Dexamethasone alone following treatment with Levofloxacin + Dexamethasone
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Levofloxacin + Dexamethasone Followed by Dexamethasone
    Reporting group description
    		 Levofloxacin + dexamethasone ophthalmic solution containing levofloxacin hemihydrate 5.12 mg/ml, corresponding to levofloxacin 5 mg/ml, and dexamethasone sodium phosphate 1.32 mg/ml, corresponding to dexamethasone 1 mg/ml (L-DSP), followed by Dexamethasone 1 mg/ml ophthalmic suspension (Maxidex) Dose and regimen: Levofloxacin + dexamethasone sodium phosphate eye drops for 7 days, 1 x 30 μl drop - 4 times a day, followed by dexamethasone eye drops (Maxidex) for an additional 7 days, 1 drop - 4 times a day.

    Reporting group title
    Tobramycin + Dexamethasone
    Reporting group description
    		 Tobramycin 3 mg/ml + dexamethasone 1 mg/ml eye drops suspension (Tobradex) Dose and regimen: 1 drop - 4 times a day for 14 days

    Serious adverse events
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 395 (1.01%)
    2 / 393 (0.51%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 395 (0.51%)
    1 / 393 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial Infarction
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 393 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Eye disorders
    Retinal Detachment
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 393 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Levofloxacin + Dexamethasone Followed by Dexamethasone Tobramycin + Dexamethasone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    52 / 395 (13.16%)
    49 / 393 (12.47%)
    General disorders and administration site conditions
    Disorders not specified
    Additional description: Tables for SOC and PT have not been required for non-serious adverse events but have been carried out for all adverse events (serious and non serious adverse events togheter) and only for serious events.
         subjects affected / exposed
    52 / 395 (13.16%)
    49 / 393 (12.47%)
         occurrences all number
    52
    49

    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? No

    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-Thu May 02 07:22:46 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA