The purpose of this study is to find a dose of intravitreal bevacizumab that is lower than currently used for severe retinopathy of prematurity (ROP), is effective in this study, and can be tested in future larger studies.
Despite promising initial results using empirical doses of bevacizumab based on half the adult dose for treatment of acute severe ROP, little is known about lower doses of bevacizumab for ROP. An increasing number of ophthalmologists are treating premature infants with severe ROP using bevacizumab. Given the potential systemic and ocular adverse effects of intravitreal bevacizumab injections, determining a lower effective dose of bevacizumab is an important next step. The proposed study will test progressively lower doses to find a dose to take forward to a future larger study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
120
Varying dosages in 10µl
The Emory Eye Center
Atlanta, Georgia, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Wilmer Institute
Baltimore, Maryland, United States
Number of Participants With Successful Treatment of ROP
Success is defined as improvement\* by the 4-day exam and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks of injection. \* For infants with plus disease, improvement by the 4-day post-injection exam is defined as plus disease no longer being present. For infants with type 1 ROP without plus disease (i.e., zone I, stage 3), improvement by the 4-day post-injection exam is defined as: (1) a significant reduction in severity and/or extent of extraretinal neovascularization, and, (2) if pre-plus was present pre-injection, reduction in the degree of abnormal vascular dilation and/or tortuosity. A dose will be considered effective if it successfully treats at least 80% of subjects.
Time frame: 4 weeks post-injection
Distribution of VEGF Levels
The parents of each infant enrolled in the study will be given the option to participate in a study to measure levels of vascular endothelial growth factor (VEGF) and Avastin in the plasma. Participants in this optional study will have blood collected for analysis The distribution of VEGF and Avastin levels (median, range, and quartiles) will be described before injection, and at 2 weeks and 4 weeks post-injection. For each dosage level, at 2, and 4-weeks post-injection, the change from pre-injection will be calculated.
Time frame: 2 weeks post-injection
Distribution of VEGF Levels
The parents of each infant enrolled in the study will be given the option to participate in a study to measure levels of VEGF and Avastin in the plasma. Participants in this optional study will have blood collected for analysis The distribution of VEGF and Avastin levels (median, range, and quartiles) will be described before injection, and at 2 weeks and 4 weeks post-injection. For each dosage level, at 2, and 4-weeks post-injection, the change from pre-injection will be calculated.
Time frame: 4 weeks post-injection
Distribution of Avastin Levels
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Boston Children's Hospital
Boston, Massachusetts, United States
Duke University Eye Center
Durham, North Carolina, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, United States
Pediatric Ophthalmology Associates, Inc.
Columbus, Ohio, United States
Dean A. McGee Eye Institute, University of Oklahoma
Oklahoma City, Oklahoma, United States
Texas Children's Hospital - Dept. Of Ophthalmology
Houston, Texas, United States
University of Utah Moran Eye Center
Salt Lake City, Utah, United States
...and 1 more locations
The parents of each infant enrolled in the study will be given the option to participate in a study to measure levels of VEGF and Avastin in the plasma. Participants in this optional study will have blood collected for analysis The distribution of VEGF and Avastin levels (median, range, and quartiles) will be described before injection, and at 2 weeks and 4 weeks post-injection. For each dosage level, at 2, and 4-weeks post-injection, the change from pre-injection will be calculated, and a 95% confidence interval calculated for the change.
Time frame: 2 weeks post-injection
Distribution of Avastin Levels
The parents of each infant enrolled in the study will be given the option to participate in a study to measure levels of VEGF and Avastin in the plasma. Participants in this optional study will have blood collected for analysis The distribution of VEGF and Avastin levels (median, range, and quartiles) will be described before injection, and at 2 weeks and 4 weeks post-injection. For each dosage level, at 2, and 4-weeks post-injection, the change from pre-injection will be calculated, and a 95% confidence interval calculated for the change.
Time frame: 4 weeks post-injection
Number of Study Eyes Requiring Additional Treatment/s for ROP
12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
Time frame: 12-month corrected age
Any Adverse Events or Complications Since the 4-week Exam
12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
Time frame: 12-month corrected age
Visual Fixation Status at 12 Months
12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
Time frame: 12-month corrected age
Proportion of Infants for Whom at Least One Event Was Reported
Adverse events reported at any time during the study will be tabulated for all enrolled infants and coded using the MedRA system. For each dosage level, an estimate and 95% confidence interval of the proportions will be obtained using the exact binomial method 12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
Time frame: Enrollment to 12-month corrected age
Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug
Adverse events reported at any time during the study will be tabulated for all enrolled infants and coded using the MedRA system. For each dosage level, an estimate and 95% confidence interval of the proportions will be obtained using the exact binomial method 12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
Time frame: Enrollment to 12-month corrected age
Count of Infants for Whom at Least One Serious Adverse Event Was Reported
Adverse events reported at any time during the study will be tabulated for all enrolled infants and coded using the MedRA system. For each dosage level, an estimate and 95% confidence interval of the proportions will be obtained using the exact binomial method.
Time frame: Enrollment to 12-month corrected age
Number of Infant Deaths
Adverse events reported at any time during the study will be tabulated for all enrolled infants and coded using the MedRA system. 12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
Time frame: Enrollment to 12-month corrected age
Number of Infants With 24-Month Extended Follow Up Exam
A subset of infants enrolled in ROP1 will have extended follow up consisting of one additional office exam with developmental testing. This testing will provide a cross-sectional evaluation of visual acuity, refractive error, and development at the adjusted age 24-month visit. 24-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 24 months.
Time frame: 24-month corrected age
Number of Fellow Eyes Requiring Additional Treatment/s for ROP
12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
Time frame: 12-month corrected age