Retinopathy of PrematurityPhase 3ROP3NCT04634604
A Randomized Trial of Low-Dose Bevacizumab vs Laser for Type 1 ROP
A Phase 3 study testing Bevacizumab and Laser in people with Retinopathy of Prematurity, run by Jaeb Center for Health Research at 35 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 6 months
- Conditions the study is for
- Retinopathy of Prematurity
- What is being tested?
- Bevacizumab and Laser
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 35 sitesin 2 countries
- Study dates
- 27 Apr 2022to 14 Aug 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
35 sites in 2 countries.
35 sites in 2 countries
United States32 sites
The Emory Eye Center
Atlanta, Georgia, 30322
University of Colorado Health Sciences Center
Aurora, Colorado, 80045
Greater Baltimore Medical Center
Baltimore, Maryland, 21204-5809
Boston Children's Hospital
Boston, Massachusetts, 02215
University of North Carolina
Chapel Hill, North Carolina, 27599
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
U of Illinois at Chicago Eye and Ear Infirmary
Chicago, Illinois, 60612
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
University of Missouri- Columbia Mason Eye Institute
Columbia, Missouri, 65201
Pediatric Ophthalmology Associates, Inc.
Columbus, Ohio, 43205
Denver Health and Hospital Authority
Denver, Colorado, 80204
Duke University Eye Center
Durham, North Carolina, 27710
Connecticut Childrens Medical Center
Farmington, Connecticut, 06032
Texas Children's Hospital - Dept. Of Ophthalmology
Houston, Texas, 77030
The Woman's Hospital of Texas
Houston, Texas, 77054
University of Chicago
Hyde Park, Illinois, 60637
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Riley Hospital for Children
Indianapolis, Indiana, 46202
Univ of California, Irvine- Gavin Herbert Eye Institute
Irvine, California, 92697
UK Ophthalmology and Visual Sciences, The Eye Clinic
Lexington, Kentucky, 40508
Arkansas Childrens Hospital/ University of Arkansas Medical Sciences
Little Rock, Arkansas, 72202
Storm Eye Institute
Mt. Pleasant, South Carolina, 29464
New York Presbyterian David H Koch Center
New York, New York, 10065
Virginia Pediatric Eye Center
Norfolk, Virginia, 23502
Children's Hospital & Medical Center
Omaha, Nebraska, 68114
Arizonia Pediatric Eye Specialists
Phoenix, Arizona, 85006
UPMC Children's Eye Center of Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Casey Eye Institute
Portland, Oregon, 97239
University of California, Davis
Sacramento, California, 95817
University of Utah Moran Eye Center
Salt Lake City, Utah, 84132
University of California San Francisco Department of Ophthalmology
San Francisco, California, 94143
St. Louis University Ophthalmology
St Louis, Missouri, 63104
Canada3 sites
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
CHU - Sainte-Justine
Montreal, Quebec, H3T 1C5
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Official title: A Randomized Trial of Low-Dose Bevacizumab Versus Laser for Type 1 Retinopathy of Prematurity
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.
Read the 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.
- Conditions
- Retinopathy of Prematurity
- Being tested
- Bevacizumab, Laser
- Medical subject headings
- Retinopathy of Prematurity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
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.
LaserProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Laser | Active comparator | 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. Receives: Procedure: Laser |
| Bevacizumab | Experimental | 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. Receives: Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 Months Adjusted Age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2020
- Study start27 Apr 2022
- Primary completion14 Aug 2023
- Study completion14 Aug 2023
Why it stopped: Lack of feasibility to recruit.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Retinopathy of PrematurityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jaeb Center for Health Research
- Sponsor type
- University, hospital or other
- Collaborators
- Pediatric Eye Disease Investigator Group, National Eye Institute (NEI)
- Responsible party
- Sponsor
- Investigators
- David K Wallace, MD, MPH, Study chair, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04634604
- Sponsor's protocol ID
- ROP3
- Other IDs
- UG1EY011751
- Acronym
- ROP3
- Status last verified
- May 2026
- First submitted
- 16 Nov 2020
- Last updated
- 14 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Yes In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the Pediatric Eye Disease Investigator Group (PEDIG) public website after the completion of each protocol and publication of the primary manuscript.
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Low-Dose Bevacizumab Versus Laser for Type 1 Retinopathy of Prematurity
- ClinicalTrials.gov ID
- NCT04634604
- Acronym / sponsor ID
- ROP3 / ROP3
- Conditions
- Retinopathy of Prematurity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of feasibility to recruit.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Jaeb Center for Health ResearchUniversity, hospital or other
- Collaborators
- Pediatric Eye Disease Investigator Group, National Eye Institute (NEI)
- Study start
- 27 Apr 2022 (actual)
- Primary completion
- 14 Aug 2023 (actual)
- Study completion
- 14 Aug 2023 (actual)
- First posted
- 18 Nov 2020 (actual)
- Results
- Posted 1 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Laser | Active comparator | Procedure: LaserFor 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. |
| Bevacizumab | Experimental | Drug: BevacizumabFor 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. |
Who may qualify
- Ages
- Up to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Birth weight < 1251 grams
- Newly diagnosed (within 2 days) type 1 ROP in one or both eyes; meeting the following criteria:
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: AvastinFor 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 |
| LaserFor 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. | Procedure or surgery | Laser |
Primary outcome
Treatment Success Rate At 6 Months Adjusted Age
Time frame: 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- PEDIG Public WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Yes In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the Pediatric Eye Disease Investigator Group (PEDIG) public website after the completion of each protocol and publication of the primary manuscript.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David K Wallace, MD, MPH study chair
Indiana University
35 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bevacizumab and Laser in people with Retinopathy of Prematurity, run by Jaeb Center for Health Research at 35 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Success Rate At 6 Months Adjusted Age (time frame: 6 Months Adjusted Age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.