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Ranibizumab For Persistent Diabetic Macular Edema After Bevacizumab (ROTATE)

Primary Purpose

Diabetic Macular Edema

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ranibizumab 0.3mg/0.05cc
Sponsored by
Southeast Retina Center, Georgia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Macular Edema

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Ability to provide written informed consent and comply with study assessments for the full duration of the study.
  • >=18 years
  • Type I/II diabetes mellitus
  • Central-involved DME in study eye (OCT CSF >=275um on Heidelberg Spectralis spectral domain OCT with evidence of intraretinal or subretinal fluid or cysts)
  • Definite retinal thickening due to diabetic macular edema involving the center of the macula.
  • Media clarity, pupillary dilation and individual cooperation for adequate fungus photography and fluorescein angiography.
  • Visual Acuity score in study eye <=80 and >=20 (approximate Snellen equivalent 20/25 to 20/400).
  • History of at least 6 intravitreal bevacizumab injections within the past 9 months and 2 intravitreal bevacizumab injections within the past 2 months.
  • No history of an anti-VEGF treatment for DME in the past 3 weeks.
  • No other DME treatment for DME, other than bevacizumab, in the study eye at any time in the past 3 months.
  • No history of major ocular surgery in the study eye within prior 3 months or anticipated within the next six months following randomization.

Exclusion Criteria:

  • Pregnancy or lactation
  • Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
  • Participation in another medical investigation or trial within 30 days of randomization
  • Known allergy to ranibizumab
  • Acute cardiovascular event requiring hospitalization within the past 3 months
  • Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization or anticipated use during the study
  • Macular edema is considered to be due to a cause other than DME
  • An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from the resolution of macular edema
  • History of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agent other than bevacizumab within 9 months prior to randomization
  • History of panretinal photocoagulation within 3 months prior to randomization or anticipated need for panretinal photocoagulation in the 6 months following randomization
  • Yag capsulotomy performed within 1 month prior to randomization
  • External ocular infection including conjunctivitis, significant blepharitis, etc.

Sites / Locations

  • Southeast Retina Center, PCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ranibizumab 0.3mg (12 months)

Ranibizumab 0.3mg (6 months)

Arm Description

Intravitreal injection of ranibizumab 0.3mg/0.05cc

Intravitreal injection of ranibizumab 0.3mg/0.05cc

Outcomes

Primary Outcome Measures

Incidence of ocular and systemic adverse events will be compared between experimental and active comparator groups
Examples include worsened acuity of greater than 30 letters, retinal detachment, endophthalmitis, cataract progression, vitreous hemorrhage, new PDR or neovascularization of the iris or angle, incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs and will include thromboembolic events, deaths and systemic serious adverse events
Severity of ocular and systemic adverse events will be compared between experimental and active comparator groups
Examples include worsened acuity of greater than 30 letters, retinal detachment, endophthalmitis, cataract progression, vitreous hemorrhage, new PDR or neovascularization of the iris or angle, incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs and will include thromboembolic events, deaths and systemic serious adverse events

Secondary Outcome Measures

Efficacy of monthly and monthly followed by PRN dosing of 0.3 mg ranibizumab after persistent DME despite previous bevacizumab therapy
Examples include proportion of eyes with absence of fluorescein angiographic macular leakage at 12 months; proportion of eyes with unchanged, worsened, or improved fluorescein angiographic macular leakage from baseline at 1, 6 and 12 months; proportion of eyes with unchanged, worsened, or improved fundus photographic DME appearance from baseline at 1, 6 and 12 months; proportion of eyes with new vitreous hemorrhage or traction retinal detachment secondary to Proliferative Diabetic Retinopathy (PDR); proportion of eyes with progression from baseline Non-proliferative Diabetic Retinopathy (NPDR) to PDR

Full Information

First Posted
April 2, 2013
Last Updated
September 16, 2014
Sponsor
Southeast Retina Center, Georgia
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01845844
Brief Title
Ranibizumab For Persistent Diabetic Macular Edema After Bevacizumab
Acronym
ROTATE
Official Title
Ranibizumab For Persistent Diabetic Macular Edema After Bevacizumab (ROTATE Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Unknown status
Study Start Date
April 2013 (undefined)
Primary Completion Date
January 2015 (Anticipated)
Study Completion Date
January 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Southeast Retina Center, Georgia
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is an open-label, Phase I/II study of Intravitreally administered 0.3mg ranibizumab in subjects with persistent Diabetic Macular Edema (DME) after recent and frequent bevacizumab (at least 2 bevacizumab intravitreal injections within 2 months prior to enrollment and at least 6 bevacizumab injections within 9 months of enrollment).
Detailed Description
30 eyes will be randomized in a 1:2 ratio (Group A= 10 patients; Group B= 20 patients) Group A: ("monthly group")- Consented patient with enrolled eye will receive 12 monthly required injections of 0.3mg ranibizumab over 1 year OR Group B: ("As needed (PRN) Group")- Consented patient with enrolled eye will receive 6 monthly required injections of 0.3mg ranibizumab for 6 months, followed by as needed (PRN) dosing (required ranibizumab if DME persistent on Optical Coherence Tomography (OCT) and Early Treatment Diabetic Retina Study (ETDRS) Best Corrected Visual Acuity (BCVA) <20/20) for 6 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Macular Edema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ranibizumab 0.3mg (12 months)
Arm Type
Experimental
Arm Description
Intravitreal injection of ranibizumab 0.3mg/0.05cc
Arm Title
Ranibizumab 0.3mg (6 months)
Arm Type
Active Comparator
Arm Description
Intravitreal injection of ranibizumab 0.3mg/0.05cc
Intervention Type
Drug
Intervention Name(s)
Ranibizumab 0.3mg/0.05cc
Other Intervention Name(s)
Lucentis
Intervention Description
Group A (Arm A) will receive monthly 0.3mg/0.05cc intravitreal injections for 12 consecutive months. Group B (Arm B) will receive monthly 0.3mg/0.05cc intravitreal injections for the first six months and then PRN for the remaining 6 months per protocol specified criteria.
Primary Outcome Measure Information:
Title
Incidence of ocular and systemic adverse events will be compared between experimental and active comparator groups
Description
Examples include worsened acuity of greater than 30 letters, retinal detachment, endophthalmitis, cataract progression, vitreous hemorrhage, new PDR or neovascularization of the iris or angle, incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs and will include thromboembolic events, deaths and systemic serious adverse events
Time Frame
1 year
Title
Severity of ocular and systemic adverse events will be compared between experimental and active comparator groups
Description
Examples include worsened acuity of greater than 30 letters, retinal detachment, endophthalmitis, cataract progression, vitreous hemorrhage, new PDR or neovascularization of the iris or angle, incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs and will include thromboembolic events, deaths and systemic serious adverse events
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Efficacy of monthly and monthly followed by PRN dosing of 0.3 mg ranibizumab after persistent DME despite previous bevacizumab therapy
Description
Examples include proportion of eyes with absence of fluorescein angiographic macular leakage at 12 months; proportion of eyes with unchanged, worsened, or improved fluorescein angiographic macular leakage from baseline at 1, 6 and 12 months; proportion of eyes with unchanged, worsened, or improved fundus photographic DME appearance from baseline at 1, 6 and 12 months; proportion of eyes with new vitreous hemorrhage or traction retinal detachment secondary to Proliferative Diabetic Retinopathy (PDR); proportion of eyes with progression from baseline Non-proliferative Diabetic Retinopathy (NPDR) to PDR
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Mean BCVA letter score
Description
◦Mean BCVA letter changes from baseline at 1, 3, 6, 9 and 12 months
Time Frame
Baseline, 1, 3, 6, 9, and 12 months
Title
Mean OCT CSF thickness and macular volume
Description
OCT Central Subfield (CSF) thickness and macular volume mean changes from baseline at 1, 3, 6, 9 and 12 months
Time Frame
Baseline, 1, 3, 6, 9, and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Ability to provide written informed consent and comply with study assessments for the full duration of the study. >=18 years Type I/II diabetes mellitus Central-involved DME in study eye (OCT CSF >=275um on Heidelberg Spectralis spectral domain OCT with evidence of intraretinal or subretinal fluid or cysts) Definite retinal thickening due to diabetic macular edema involving the center of the macula. Media clarity, pupillary dilation and individual cooperation for adequate fungus photography and fluorescein angiography. Visual Acuity score in study eye <=80 and >=20 (approximate Snellen equivalent 20/25 to 20/400). History of at least 6 intravitreal bevacizumab injections within the past 9 months and 2 intravitreal bevacizumab injections within the past 2 months. No history of an anti-VEGF treatment for DME in the past 3 weeks. No other DME treatment for DME, other than bevacizumab, in the study eye at any time in the past 3 months. No history of major ocular surgery in the study eye within prior 3 months or anticipated within the next six months following randomization. Exclusion Criteria: Pregnancy or lactation Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated Participation in another medical investigation or trial within 30 days of randomization Known allergy to ranibizumab Acute cardiovascular event requiring hospitalization within the past 3 months Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization or anticipated use during the study Macular edema is considered to be due to a cause other than DME An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from the resolution of macular edema History of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agent other than bevacizumab within 9 months prior to randomization History of panretinal photocoagulation within 3 months prior to randomization or anticipated need for panretinal photocoagulation in the 6 months following randomization Yag capsulotomy performed within 1 month prior to randomization External ocular infection including conjunctivitis, significant blepharitis, etc.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dennis M Marcus, M.D.
Phone
706-650-0061
Email
dmarcus@southeastretina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dennis M Marcus, M.D.
Organizational Affiliation
Southeast Retina Center
Official's Role
Study Director
Facility Information:
Facility Name
Southeast Retina Center, PC
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30909
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dennis M Marcus, MD
Phone
706-650-0061
Email
dmarcus@southeastretina.com
First Name & Middle Initial & Last Name & Degree
Jared Gardner, BS
Phone
706-650-0061
Email
jgardner@southeastretina.com
First Name & Middle Initial & Last Name & Degree
Dennis M Marcus, M.D.
First Name & Middle Initial & Last Name & Degree
Harinderjit Singh, M.D.

12. IPD Sharing Statement

Learn more about this trial

Ranibizumab For Persistent Diabetic Macular Edema After Bevacizumab

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