Bevacizumab Treatment For Type 1 ROP (ROP4)

Bevacizumab Treatment For Type 1 Retinopathy of Prematurity

Type 1 retinopathy of prematurity in zone I represents the most severe type of ROP and has the worst prognosis. It is unknown whether low-dose bevacizumab will be successful in these severe cases. Also unknown is the timing and extent of peripheral retinal vascularization after low-dose bevacizumab compared with the standard dose. The current study will evaluate whether doses of 0.063 mg and 0.25mg are effective as treatment for type 1 ROP, with ROP and retinal vessels all in zone I.

Study Overview

• Status: Active, not recruiting
• Conditions: Retinopathy of Prematurity
• Intervention / Treatment: Drug: Bevacizumab

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 either intravitreous bevacizumab 0.25 mg. Study exams will be at 1 day, 4 days (if no improvement on day 1), 1, 2, 3, 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 and 12 months. Non-study examinations will be at clinician discretion and are likely to occur more often. The primary outcome will be treatment success within each dose group, defined as improvement by the day 4 exam and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks of injection. Important secondary outcomes include safety and efficacy. refractive outcomes, and the extent of retinal vascularization at 2 and 4 months post-injection between the two dose groups.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Childrens Hospital/ University of Arkansas Medical Sciences
  • California
    • Irvine, California, United States, 92697
      • Univ of California, Irvine- Gavin Herbert Eye Institute
    • Los Angeles, California, United States, 90095
      • Jules Stein Eye Institute at the University of California, Los Angeles
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • San Francisco, California, United States, 94143
      • University of California San Francisco Department of Ophthalmology
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Eye Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Chicago, Illinois, United States, 60612
      • U of Illinois at Chicago Eye and Ear Infirmary
    • Hyde Park, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • UK Ophthalmology and Visual Sciences, The Eye Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21204-5809
      • Greater Baltimore Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston Children's Hospital
  • New York
    • New York, New York, United States, 10065
      • New York Presbyterian David H Koch Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Eye Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Pediatric Ophthalmology Associates, Inc.
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Eye Center of Children's Hospital of Pittsburgh
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
      • Storm Eye Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital - Dept. Of Ophthalmology
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Moran Eye Center
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Pediatric Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The study participant must have at least one eye meeting all of the inclusion criteria in order to be eligible to participate:

1. Birth weight < 1251 grams
2. Newly diagnosed (within 2 days) type 1 ROP in zone I in one or both eyes

Exclusion Criteria:

Participants meeting any of the following exclusion criteria will be excluded from study participation.

1. Previous treatment for ROP
2. Stage 4 or 5 ROP in either eye
3. Treatment could not be done within 2 days of diagnosis of type 1 ROP
4. Investigator unwilling to randomize or parent unwilling to accept randomized assignment to either treatment
5. Transfer to another hospital anticipated within the next 4 weeks where exams by study-certified examiners are not available. If hospital discharge is anticipated within the next 4 weeks, parents unable or unwilling to return to the PEDIG site for outpatient follow-up visits.
6. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab- 0.063 mg; Participants will receive a single intravitreal injection of 0.063 mg of bevacizumab in one or both eyes following enrollment into the study. The injection/s should be given as soon as possible but no later than 2 days after the diagnosis of type 1 ROP meeting all of the inclusion criteria and none of the exclusion criteria.	Drug: Bevacizumab; All participants will receive a single intravitreal injection of bevacizumab in one or both eyes following enrollment into the study. The injection/s should be given as soon as possible but no later than 2 days after the diagnosis of type 1 ROP meeting all of the inclusion criteria and none of the exclusion criteria. Eyes meeting eligibility criteria will receive a single dose of 0.063 mg or 0.25mg bevacizumab provided by the pharmacy at the investigator's institution.; Other Names: Avastin
Experimental: Bevacizumab- 0.25 mg; Participants will receive a single intravitreal injection of 0.25 mg of bevacizumab in one or both eyes following enrollment into the study. The injection/s should be given as soon as possible but no later than 2 days after the diagnosis of type 1 ROP meeting all of the inclusion criteria and none of the exclusion criteria.	Drug: Bevacizumab; All participants will receive a single intravitreal injection of bevacizumab in one or both eyes following enrollment into the study. The injection/s should be given as soon as possible but no later than 2 days after the diagnosis of type 1 ROP meeting all of the inclusion criteria and none of the exclusion criteria. Eyes meeting eligibility criteria will receive a single dose of 0.063 mg or 0.25mg bevacizumab provided by the pharmacy at the investigator's institution.; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Success at 4 Weeks Post Injection	Treatment success, determined at 4 weeks, post injection, and meeting all the following criteria: Improvement by the 4-day exam (3 to 5 days); No recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks of injection.	4 weeks

Collaborators and Investigators

• Sponsor: Jaeb Center for Health Research
• Collaborators: National Eye Institute (NEI); Pediatric Eye Disease Investigator Group
• Investigators: Study Chair: David K Wallace, MD, MPH, Vanderbilt University

Publications and helpful links

Helpful Links

• PEDIG Public Website

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Actual): July 1, 2025
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infant, Premature, Diseases; Infant, Newborn, Diseases; Eye Diseases; Retinal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinopathy of Prematurity; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab
• Other Study ID Numbers: ROP4; UG1EY011751 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: Data will be made available after publication of each primary manuscript.
• IPD Sharing Access Criteria: Users accessing the data must enter an email address.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No