NCT04634604

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Apr 2022

Shorter than P25 for phase_3

Geographic Reach
2 countries

35 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 16, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 18, 2020

Completed
1.4 years until next milestone

Study Start

First participant enrolled

April 27, 2022

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 14, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 14, 2023

Completed
12 months until next milestone

Results Posted

Study results publicly available

August 1, 2024

Completed
Last Updated

August 1, 2024

Status Verified

July 1, 2024

Enrollment Period

1.3 years

First QC Date

November 16, 2020

Results QC Date

June 24, 2024

Last Update Submit

July 29, 2024

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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

Study Arms (2)

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.

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.

Drug: Bevacizumab

Interventions

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.

Also known as: Avastin
Bevacizumab
LaserPROCEDURE

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.

Laser

Eligibility Criteria

AgeUp to 6 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (35)

Arizonia Pediatric Eye Specialists

Phoenix, Arizona, 85006, United States

Location

Arkansas Childrens Hospital/ University of Arkansas Medical Sciences

Little Rock, Arkansas, 72202, United States

Location

Univ of California, Irvine- Gavin Herbert Eye Institute

Irvine, California, 92697, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

University of California San Francisco Department of Ophthalmology

San Francisco, California, 94143, United States

Location

University of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Denver Health and Hospital Authority

Denver, Colorado, 80204, United States

Location

Connecticut Childrens Medical Center

Farmington, Connecticut, 06032, United States

Location

The Emory Eye Center

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

U of Illinois at Chicago Eye and Ear Infirmary

Chicago, Illinois, 60612, United States

Location

University of Chicago

Hyde Park, Illinois, 60637, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

UK Ophthalmology and Visual Sciences, The Eye Clinic

Lexington, Kentucky, 40508, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204-5809, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

University of Missouri- Columbia Mason Eye Institute

Columbia, Missouri, 65201, United States

Location

St. Louis University Ophthalmology

St Louis, Missouri, 63104, United States

Location

Children's Hospital & Medical Center

Omaha, Nebraska, 68114, United States

Location

New York Presbyterian David H Koch Center

New York, New York, 10065, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Eye Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Pediatric Ophthalmology Associates, Inc.

Columbus, Ohio, 43205, United States

Location

Casey Eye Institute

Portland, Oregon, 97239, United States

Location

UPMC Children's Eye Center of Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Storm Eye Institute

Mt. Pleasant, South Carolina, 29464, United States

Location

Texas Children's Hospital - Dept. Of Ophthalmology

Houston, Texas, 77030, United States

Location

The Woman's Hospital of Texas

Houston, Texas, 77054, United States

Location

University of Utah Moran Eye Center

Salt Lake City, Utah, 84132, United States

Location

Virginia Pediatric Eye Center

Norfolk, Virginia, 23502, United States

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

CHU - Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Links

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

BevacizumabLasers

Condition Hierarchy (Ancestors)

Retinal DiseasesEye DiseasesInfant, Premature, DiseasesInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsOptical DevicesEquipment and SuppliesRadiation Equipment and Supplies

Limitations and Caveats

Early termination leading to small numbers of subjects which precluded statistical analysis. Active participants were released from study at time of study termination.

Results Point of Contact

Title
Ray Kraker
Organization
Jaeb Center for Health Research

Study Officials

  • David K Wallace, MD, MPH

    Indiana University

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 16, 2020

First Posted

November 18, 2020

Study Start

April 27, 2022

Primary Completion

August 14, 2023

Study Completion

August 14, 2023

Last Updated

August 1, 2024

Results First Posted

August 1, 2024

Record last verified: 2024-07

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Data will be made available after publication of each primary manuscript.
Access Criteria
Users accessing the data must enter an email address.

Locations