A Randomized Trial of Low-Dose Bevacizumab vs Laser for Type 1 ROP

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Trial of Low-Dose Bevacizumab Versus Laser for Type 1 Retinopathy of Prematurity

Conditions
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Retinopathy of Prematurity

Intervention / Treatment
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* Drug: Bevacizumab
* Procedure: Laser


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Laser<br>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. | Procedure: Laser<br>* 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.<br>|
| Experimental: Bevacizumab<br>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. | Drug: Bevacizumab<br>* 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.<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 6 Months Adjusted Age |