The Effect of Intravitreal Ranibizumab on Visual Acuity and Hard Exudate Resolution in the Treatment of Diabetic Macular Edema With Center Involved Edema and Lipid Exudates

Sponsor
South Coast Retina Center; Carson, McBeath, Boswell, Inc. (Other)
Overall Status
Completed
CT.gov ID
NCT02448446
Collaborator
Genentech, Inc. (Industry), Doheny Image Reading Center (Other), Retina Partners (Other)
25
4
2
33
6.3
0.2

Study Details

Study Description

Brief Summary

This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab in subjects with diabetic macular edema and lipid exudates in the central subfield.

Condition or Disease Intervention/Treatment Phase
  • Drug: ranibizumab 0.3mg
Phase 1/Phase 2

Detailed Description

This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab in subjects with diabetic macular edema and lipid exudates in the central subfield.

Consented, enrolled subjects will receive multiple open-label intravitreal injections on 0.3mg ranibizumab administered every 30 days for 12 months per the treatment algorithm.

The patients will be randomized to 1 of 2 treatment groups. Group 1: Treatment algorithm based on the Diabetic Retinopathy Clinical Research (DRCR) protocol I 4:2:7 strategy based on the presence of macular edema.

Group 2: Continue treatment until not only the macular edema is resolved but also until the lipid exudate is resolved.

Sample size: 30 eyes Follow-up Schedule: Every 4 weeks throughout the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
25 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Effect of Intravitreal Ranibizumab on Visual Acuity and Hard Exudate Resolution in the Treatment of Diabetic Macular Edema With Foveal Involving Edema and Lipid Exudates
Study Start Date :
Aug 1, 2015
Actual Primary Completion Date :
May 1, 2018
Actual Study Completion Date :
May 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Diabetic macular edema treatment group (Group 1)

Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema.

Drug: ranibizumab 0.3mg
intravitreally administered
Other Names:
  • Lucentis
  • Active Comparator: Diabetic macular edema and lipid treatment group (Group 2)

    Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved.

    Drug: ranibizumab 0.3mg
    intravitreally administered
    Other Names:
  • Lucentis
  • Outcome Measures

    Primary Outcome Measures

    1. Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months [6-12 months]

      Compare Group 1 and Group 2 for best correct visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters.

    Secondary Outcome Measures

    1. Percentage of Eyes With Improvement of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography [12 months]

    2. Percentage of Eyes With Complete Resolution of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography [12 months]

    3. Number of Eyes With Complete Resolution in the Central Subfield as Measured on OCT and Fundus Photography [12 months]

    4. Percentage of Eyes With Improvement in Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography [12 months]

    5. Percentage of Patients With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured on OCT and Fundus Photography [12 months]

    6. Number of Eyes With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography [12 months]

    7. Incidence and Severity of Ocular Adverse Events as a Measure of Safety and Tolerability [12 months]

    8. Incidence and Severity of Other Adverse Events as a Measure of Safety and Tolerability [12 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Subjects will be eligible if the following criteria are met:

    Inclusion Criteria

    • Ability to provide written informed consent and comply with study assessments for the full duration of the study

    • Age ≥ 18 years

    • Type 1 or Type 2 Diabetes mellitus

    • Best corrected ETDRS visual acuity (20/32-20/320) or letter score 78 to 24

    • Diabetic macular edema on clinical examination involving the center of the macula assessed to be the main cause of visual loss

    • Retinal thickness measured on spectral domain optical coherence tomography (OCT). Zeiss Cirrus: ≥290μm in women and ≥305 μm in men in the central subfield. Heidelberg Spectralis: ≥305μm in women and ≥320 μm in men in the central subfield

    • Lipid exudates involving the central subfield on spectral domain OCT.

    Exclusion Criteria

    Subjects who meet any of the following criteria will be excluded from this study:
    • Treatment for diabetic macular edema within the prior 4 months.

    • Panretinal photocoagulation within the prior 4 months or anticipated need for panretinal photocoagulation within the next 6 months

    • major ocular surgery within the prior 4 months

    • myocardial infarction, other cardiac event requiring hospitalization, cerebrovascular accident, transient ischemic attack, or treatment for acute congestive heart failure occurred within 4 months before randomization

    • Pregnancy (positive pregnancy test) or lactation

    • Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an intrauterine device (IUD), or contraceptive hormone implant or patch.

    • Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated

    • Participation in another simultaneous medical investigation or trial

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 South Coast Retina Center; Carson, McBeath, Boswell, Inc Huntington Beach California United States 92647
    2 South Coast Retina Center; Carson, McBeath, and Boswell, Inc Long Beach California United States 90505
    3 Retina Partners Santa Monica California United States 90404
    4 South Coast Retina Center; Carson, McBeath, Boswell, Inc Torrance California United States 90505

    Sponsors and Collaborators

    • South Coast Retina Center; Carson, McBeath, Boswell, Inc.
    • Genentech, Inc.
    • Doheny Image Reading Center
    • Retina Partners

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Julie Gasperini, M.D., Medical Doctor, South Coast Retina Center; Carson, McBeath, Boswell, Inc.
    ClinicalTrials.gov Identifier:
    NCT02448446
    Other Study ID Numbers:
    • ML259577
    First Posted:
    May 19, 2015
    Last Update Posted:
    Jul 8, 2021
    Last Verified:
    Jul 1, 2021
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Period Title: Overall Study
    STARTED 13 12
    COMPLETED 12 12
    NOT COMPLETED 1 0

    Baseline Characteristics

    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2) Total
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered Total of all reporting groups
    Overall Participants 12 12 24
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    8
    66.7%
    7
    58.3%
    15
    62.5%
    >=65 years
    4
    33.3%
    5
    41.7%
    9
    37.5%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64.5
    (8.46)
    67
    (8.83)
    65.75
    (8.65)
    Sex: Female, Male (Count of Participants)
    Female
    6
    50%
    8
    66.7%
    14
    58.3%
    Male
    6
    50%
    4
    33.3%
    10
    41.7%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    12
    100%
    12
    100%
    24
    100%

    Outcome Measures

    1. Primary Outcome
    Title Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months
    Description Compare Group 1 and Group 2 for best correct visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters.
    Time Frame 6-12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Measure Participants 12 12
    Measure Eyes 12 12
    6 Months
    78
    (9.98)
    73.92
    (8.40)
    12 Months
    77.92
    (9.61)
    74.83
    (8.32)
    2. Secondary Outcome
    Title Percentage of Eyes With Improvement of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography
    Description
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Measure Participants 12 12
    Measure eyes 12 12
    Number [percentage of eyes]
    70
    83
    3. Secondary Outcome
    Title Percentage of Eyes With Complete Resolution of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography
    Description
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Measure Participants 12 12
    Measure eyes 12 12
    Number [percentage of eyes]
    60
    58
    4. Secondary Outcome
    Title Number of Eyes With Complete Resolution in the Central Subfield as Measured on OCT and Fundus Photography
    Description
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Measure Participants 12 12
    Measure eyes 12 12
    Number [eyes]
    7
    7
    5. Secondary Outcome
    Title Percentage of Eyes With Improvement in Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography
    Description
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Measure Participants 12 12
    Measure eyes 12 12
    Number [percentage of eyes]
    90
    92
    6. Secondary Outcome
    Title Percentage of Patients With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured on OCT and Fundus Photography
    Description
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Measure Participants 12 12
    Number [participants]
    0
    0%
    0
    0%
    7. Secondary Outcome
    Title Number of Eyes With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography
    Description
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Measure Participants 12 12
    Measure eyes 12 12
    Number [eyes]
    0
    0
    8. Secondary Outcome
    Title Incidence and Severity of Ocular Adverse Events as a Measure of Safety and Tolerability
    Description
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    eyes
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Measure Participants 12 12
    Count of Participants [Participants]
    0
    0%
    4
    33.3%
    9. Secondary Outcome
    Title Incidence and Severity of Other Adverse Events as a Measure of Safety and Tolerability
    Description
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    eyes
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    Measure Participants 12 12
    Count of Participants [Participants]
    9
    75%
    9
    75%

    Adverse Events

    Time Frame 1 year
    Adverse Event Reporting Description
    Arm/Group Title Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Arm/Group Description Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. ranibizumab 0.3mg: intravitreally administered Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. ranibizumab 0.3mg: intravitreally administered
    All Cause Mortality
    Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 0/12 (0%)
    Serious Adverse Events
    Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/12 (25%) 2/12 (16.7%)
    Cardiac disorders
    Low Hemoglobin 1/12 (8.3%) 1 0/12 (0%) 0
    Congestive Heart Failure 1/12 (8.3%) 1 0/12 (0%) 0
    Heart Attack 0/12 (0%) 0 1/12 (8.3%) 1
    Gastrointestinal disorders
    Cysticercosis 1/12 (8.3%) 1 0/12 (0%) 0
    Infections and infestations
    Kidney Infection 1/12 (8.3%) 1 0/12 (0%) 0
    Appendix Surgery 0/12 (0%) 0 1/12 (8.3%) 2
    Vascular disorders
    Stroke 0/12 (0%) 0 1/12 (8.3%) 1
    Other (Not Including Serious) Adverse Events
    Diabetic Macular Edema Treatment Group (Group 1) Diabetic Macular Edema and Lipid Treatment Group (Group 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/12 (75%) 9/12 (75%)
    Blood and lymphatic system disorders
    Elevated Blood Pressure 1/12 (8.3%) 1 1/12 (8.3%) 1
    Elevated Triglycerides 1/12 (8.3%) 1 0/12 (0%) 0
    Ear and labyrinth disorders
    Ear Infection 0/12 (0%) 0 1/12 (8.3%) 1
    Ear Infection 1/12 (8.3%) 1 0/12 (0%) 0
    Eye disorders
    Branch Retinal Artery Occlusion 0/12 (0%) 0 1/12 (8.3%) 1
    Central Retinal Vein Occlusion 1/12 (8.3%) 1 0/12 (0%) 0
    Ocular Hypertension 1/12 (8.3%) 1 0/12 (0%) 0
    Allergic conjunctivitis 1/12 (8.3%) 1 0/12 (0%) 0
    Subconjunctival Hemhorrage 0/12 (0%) 0 1/12 (8.3%) 1
    Visual Acuity Loss 1/12 (8.3%) 1 1/12 (8.3%) 1
    Floater 0/12 (0%) 0 1/12 (8.3%) 1
    Gastrointestinal disorders
    Nausea/Vomiting 0/12 (0%) 0 1/12 (8.3%) 1
    Immune system disorders
    Shingles 1/12 (8.3%) 1 0/12 (0%) 0
    Infections and infestations
    Influenza 0/12 (0%) 0 3/12 (25%) 3
    Sinusitis 1/12 (8.3%) 1 0/12 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastatic Tumor 1/12 (8.3%) 1 0/12 (0%) 0
    Product Issues
    Drug Administration Error 1/12 (8.3%) 1 0/12 (0%) 0
    Renal and urinary disorders
    Decreased Liver Function 0/12 (0%) 0 1/12 (8.3%) 2
    Social circumstances
    Broken Wrist 1/12 (8.3%) 1 0/12 (0%) 0
    Right Hip Injury 1/12 (8.3%) 1 0/12 (0%) 0
    Vascular disorders
    Headache 1/12 (8.3%) 1 0/12 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE 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 Dr. Julie Gasperini
    Organization South Coast Retina Center
    Phone 5629847024
    Email jgasperini@gmail.com
    Responsible Party:
    Julie Gasperini, M.D., Medical Doctor, South Coast Retina Center; Carson, McBeath, Boswell, Inc.
    ClinicalTrials.gov Identifier:
    NCT02448446
    Other Study ID Numbers:
    • ML259577
    First Posted:
    May 19, 2015
    Last Update Posted:
    Jul 8, 2021
    Last Verified:
    Jul 1, 2021