Retinopathy of Prematurity
Conditions
Brief summary
This randomized clinical trial will compare retinal outcomes with low-dose intravitreous bevacizumab (0.063 mg) versus laser photocoagulation as treatment for infants with type 1 retinopathy of prematurity (ROP). The study also will assess neurodevelopment, refractive error, visual acuity, and peripheral visual fields.
Detailed description
Infants with type 1 ROP and no prior treatment for ROP will be randomly assigned (1:1) to treatment with either intravitreous bevacizumab 0.063 mg or peripheral retinal laser ablation. Study exams will be at weeks 1, 2, and 4 weeks, and at 2 and 4-months post-treatment (and re-treatment when indicated). Additional study exams will occur at adjusted age 6 months, 1 year, and then annually for 5 more years. Non-study examinations will be at clinician discretion and are likely to occur more often. The primary outcome will be treatment success, defined as no worsening of ROP 5-13 days after treatment (or re-treatment if indicated), no plus disease or severe neovascularization 2 weeks to 6 months after treatment (or re-treatment if indicated), and no unfavorable structural outcome (or prior scleral buckle or vitrectomy) at 6 months adjusted age. Important secondary outcomes include the number of re-treatments, extent of retinal vascularization, refractive error, neurodevelopment assessed by the Bayley-4 test, IQ and neuropsychiatric testing, visual acuity, visual fields, and systemic morbidities.
Interventions
DRUGBevacizumab
For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated.
PROCEDURELaser
For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by OSHA and facility standards, will be followed.
Sponsors
Jaeb Center for Health Research
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
Healthy volunteers
No
Inclusion criteria
* Birth weight \< 1251 grams * Newly diagnosed (within 2 days) type 1 ROP in one or both eyes; meeting the following criteria: * Zone I, any stage ROP with plus disease, with retinal vessels or ROP in Zone II in any quadrant, or * Zone I, stage 3 ROP without plus disease, with retinal vessels or ROP in zone II in any quadrant or * Zone II, stage 2 or 3 ROP with plus disease
Exclusion criteria
* Previous treatment for ROP * Stage 4 or 5 ROP in either eye * All ROP in zone I in either eye (no retinal vessels or ROP extend into zone II in any quadrant) * Either treatment could not be done within 2 days of diagnosis of type 1 ROP * Investigator unwilling to randomize or parent unwilling to accept random assignment to either treatment * Transfer to another hospital not covered by study-certified examiners anticipated within the next 4 weeks * Active ocular infection or purulent nasolacrimal duct obstruction in either eye One eye will be excluded, and other eye may be eligible, if either of the following are present: * Visually significant ocular anomaly (e.g., cataract, coloboma) * Opacity that precludes an adequate view of the retina
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success Rate At 6 Months Adjusted Age | 6 Months Adjusted Age | The primary objective for the randomized trial is to determine if infants with type 1 ROP treated with intravitreal bevacizumab (subsequently referred to as BV) have a treatment success rate determined at 6 months adjusted age that is non-inferior compared with infants treated with laser photocoagulation (subsequently referred to as LASER). |
Countries
Canada, United States
Contacts
STUDY_CHAIRDavid K Wallace, MD, MPH
Indiana University
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated.
Bevacizumab: For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated. | 7 |
| Laser For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by Occupational Safety and Health Administration (OSHA) and facility standards, will be followed.
Laser: For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by OSHA and facility standards, will be followed. | 9 |
| Total | 16 |
Baseline characteristics
| Characteristic | Bevacizumab | Laser | Total |
|---|---|---|---|
| Age, Continuous | 25 weeks STANDARD_DEVIATION 1 | 24 weeks STANDARD_DEVIATION 1 | 24 weeks STANDARD_DEVIATION 1 |
| Birth Weight | 698 grams STANDARD_DEVIATION 122 | 670 grams STANDARD_DEVIATION 141 | 682 grams STANDARD_DEVIATION 129 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 7 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 9 |
| other Total, other adverse events | 4 / 7 | 6 / 9 |
| serious Total, serious adverse events | 1 / 7 | 4 / 9 |
Outcome results
Primary
Treatment Success Rate At 6 Months Adjusted Age
The primary objective for the randomized trial is to determine if infants with type 1 ROP treated with intravitreal bevacizumab (subsequently referred to as BV) have a treatment success rate determined at 6 months adjusted age that is non-inferior compared with infants treated with laser photocoagulation (subsequently referred to as LASER).
Time frame: 6 Months Adjusted Age
Population: Study terminated due to lack of feasibility of recruitment. No analyses conducted due to lack of power for analysis given small sample size.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab | Treatment Success Rate At 6 Months Adjusted Age | 3 Participants |
| Laser | Treatment Success Rate At 6 Months Adjusted Age | 4 Participants |