Clinical trial NCT01845844: Ranibizumab For Persistent Diabetic Macular Edema After Bevacizumab
Official title: Ranibizumab For Persistent Diabetic Macular Edema After Bevacizumab (ROTATE Trial)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Diabetic Macular Edema
Lead sponsor: Southeast Retina Center, Georgia
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2013-05-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of ocular and systemic adverse events will be compared between experimental and active comparator groups
timeFrame: 1 year
measure: Severity of ocular and systemic adverse events will be compared between experimental and active comparator groups
timeFrame: 1 year
Secondary outcomes:
measure: Efficacy of monthly and monthly followed by PRN dosing of 0.3 mg ranibizumab after persistent DME despite previous bevacizumab therapy
timeFrame: 1 year
Other outcomes:
measure: Mean BCVA letter score
timeFrame: Baseline, 1, 3, 6, 9, and 12 months
measure: Mean OCT CSF thickness and macular volume
timeFrame: Baseline, 1, 3, 6, 9, and 12 months
Locations:
city: Augusta
country: United States
facility: Southeast Retina Center, PC
state: Georgia
Study officials:
affiliation: Southeast Retina Center
name: Dennis M Marcus, M.D.
role: STUDY_DIRECTOR
References: