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

NCT ID: NCT04634604

Last Updated: 2024-08-01

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-27

Study Completion Date

2023-08-14

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.

Conditions

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Retinopathy of Prematurity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Laser

Intervention Type PROCEDURE

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.

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type PROCEDURE

Other Intervention Names

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Avastin

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
Maximum Eligible Age

6 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pediatric Eye Disease Investigator Group

NETWORK

Sponsor Role collaborator

National Eye Institute (NEI)

NIH

Sponsor Role collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David K Wallace, MD, MPH

Role: STUDY_CHAIR

Indiana University

Locations

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Arizonia Pediatric Eye Specialists

Phoenix, Arizona, United States

Site Status

Arkansas Childrens Hospital/ University of Arkansas Medical Sciences

Little Rock, Arkansas, United States

Site Status

Univ of California, Irvine- Gavin Herbert Eye Institute

Irvine, California, United States

Site Status

University of California, Davis

Sacramento, California, United States

Site Status

University of California San Francisco Department of Ophthalmology

San Francisco, California, United States

Site Status

University of Colorado Health Sciences Center

Aurora, Colorado, United States

Site Status

Denver Health and Hospital Authority

Denver, Colorado, United States

Site Status

Connecticut Childrens Medical Center

Farmington, Connecticut, United States

Site Status

The Emory Eye Center

Atlanta, Georgia, United States

Site Status

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

Chicago, Illinois, United States

Site Status

U of Illinois at Chicago Eye and Ear Infirmary

Chicago, Illinois, United States

Site Status

University of Chicago

Hyde Park, Illinois, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

UK Ophthalmology and Visual Sciences, The Eye Clinic

Lexington, Kentucky, United States

Site Status

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

University of Missouri- Columbia Mason Eye Institute

Columbia, Missouri, United States

Site Status

St. Louis University Ophthalmology

St Louis, Missouri, United States

Site Status

Children's Hospital & Medical Center

Omaha, Nebraska, United States

Site Status

New York Presbyterian David H Koch Center

New York, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Duke University Eye Center

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Site Status

Pediatric Ophthalmology Associates, Inc.

Columbus, Ohio, United States

Site Status

Casey Eye Institute

Portland, Oregon, United States

Site Status

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

Pittsburgh, Pennsylvania, United States

Site Status

Storm Eye Institute

Mt. Pleasant, South Carolina, United States

Site Status

Texas Children's Hospital - Dept. Of Ophthalmology

Houston, Texas, United States

Site Status

The Woman's Hospital of Texas

Houston, Texas, United States

Site Status

University of Utah Moran Eye Center

Salt Lake City, Utah, United States

Site Status

Virginia Pediatric Eye Center

Norfolk, Virginia, United States

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

CHU - Sainte-Justine

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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http://www.pedig.net

PEDIG Public Website

Other Identifiers

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UG1EY011751

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ROP3

Identifier Type: -

Identifier Source: org_study_id

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