A Randomized Trial of Low-Dose Bevacizumab vs Laser for Type 1 ROP (ROP3)

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.

Study Overview

• Status: Terminated
• Conditions: Retinopathy of Prematurity
• Intervention / Treatment: Procedure: Laser; 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 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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU - Sainte-Justine
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Arizonia Pediatric Eye Specialists
  • 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
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • San Francisco, California, United States, 94143
      • University of California San Francisco Department of Ophthalmology
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Health Sciences Center
    • Denver, Colorado, United States, 80204
      • Denver Health and Hospital Authority
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • Connecticut Childrens Medical Center
  • 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
  • Missouri
    • Columbia, Missouri, United States, 65201
      • University of Missouri- Columbia Mason Eye Institute
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University Ophthalmology
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Children's Hospital & Medical Center
  • New York
    • New York, New York, United States, 10065
      • New York Presbyterian David H Koch Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of 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
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Eye Center of Children's Hospital of Pittsburgh
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Storm Eye Institute
  • Texas
    • Houston, Texas, United States, 77054
      • The Woman's Hospital of 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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Procedure: 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.
Experimental: 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.	Drug: 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.; Other Names: Avastin

What is the study measuring?

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

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, Indiana University

Publications and helpful links

Helpful Links

• PEDIG Public Website

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2022
• Primary Completion (Actual): August 14, 2023
• Study Completion (Actual): August 14, 2023

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): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Retinal Diseases; Premature Birth; Retinopathy of Prematurity; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: ROP3; UG1EY011751 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• 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