search
Back to results

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

Primary Purpose

Retinopathy of Prematurity

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Bevacizumab
Laser
Sponsored by
Jaeb Center for Health Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Retinopathy of Prematurity

Eligibility Criteria

undefined - 6 Months (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arizonia Pediatric Eye Specialists
  • Arkansas Childrens Hospital/ University of Arkansas Medical Sciences
  • Univ of California, Irvine- Gavin Herbert Eye Institute
  • University of California, Davis
  • University of California San Francisco Department of Ophthalmology
  • University of Colorado Health Sciences Center
  • Denver Health and Hospital Authority
  • Connecticut Childrens Medical Center
  • The Emory Eye Center
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • U of Illinois at Chicago Eye and Ear Infirmary
  • University of Chicago
  • Indiana University School of Medicine
  • Riley Hospital for Children
  • UK Ophthalmology and Visual Sciences, The Eye Clinic
  • Greater Baltimore Medical Center
  • Boston Children's Hospital
  • University of Missouri- Columbia Mason Eye Institute
  • St. Louis University Ophthalmology
  • Children's Hospital & Medical Center
  • New York Presbyterian David H Koch Center
  • University of North Carolina
  • Duke University Eye Center
  • Cincinnati Children's Hospital
  • Pediatric Ophthalmology Associates, Inc.
  • Casey Eye Institute
  • UPMC Children's Eye Center of Children's Hospital of Pittsburgh
  • Storm Eye Institute
  • Texas Children's Hospital - Dept. Of Ophthalmology
  • The Woman's Hospital of Texas
  • University of Utah Moran Eye Center
  • Virginia Pediatric Eye Center
  • IWK Health Centre
  • The Hospital for Sick Children
  • CHU - Sainte-Justine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Laser

Bevacizumab

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Full Information

First Posted
November 16, 2020
Last Updated
August 22, 2023
Sponsor
Jaeb Center for Health Research
Collaborators
Pediatric Eye Disease Investigator Group, National Eye Institute (NEI)
search

1. Study Identification

Unique Protocol Identification Number
NCT04634604
Brief Title
A Randomized Trial of Low-Dose Bevacizumab vs Laser for Type 1 ROP
Acronym
ROP3
Official Title
A Randomized Trial of Low-Dose Bevacizumab Versus Laser for Type 1 Retinopathy of Prematurity
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 27, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
April 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jaeb Center for Health Research
Collaborators
Pediatric Eye Disease Investigator Group, National Eye Institute (NEI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinopathy of Prematurity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Laser
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Bevacizumab
Arm Type
Experimental
Arm Description
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
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
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
Procedure
Intervention Name(s)
Laser
Intervention Description
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.
Primary Outcome Measure Information:
Title
Treatment Success Rate At 6 Months Adjusted Age
Description
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).
Time Frame
6 Months Adjusted Age

10. Eligibility

Sex
All
Maximum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David K Wallace, MD, MPH
Organizational Affiliation
Indiana University
Official's Role
Study Chair
Facility Information:
Facility Name
Arizonia Pediatric Eye Specialists
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Arkansas Childrens Hospital/ University of Arkansas Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Univ of California, Irvine- Gavin Herbert Eye Institute
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
University of California, Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of California San Francisco Department of Ophthalmology
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Colorado Health Sciences Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Denver Health and Hospital Authority
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Connecticut Childrens Medical Center
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06032
Country
United States
Facility Name
The Emory Eye Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
U of Illinois at Chicago Eye and Ear Infirmary
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago
City
Hyde Park
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
UK Ophthalmology and Visual Sciences, The Eye Clinic
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40508
Country
United States
Facility Name
Greater Baltimore Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204-5809
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Missouri- Columbia Mason Eye Institute
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65201
Country
United States
Facility Name
St. Louis University Ophthalmology
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Children's Hospital & Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
New York Presbyterian David H Koch Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University Eye Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Pediatric Ophthalmology Associates, Inc.
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Casey Eye Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
UPMC Children's Eye Center of Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Storm Eye Institute
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
Texas Children's Hospital - Dept. Of Ophthalmology
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Woman's Hospital of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States
Facility Name
University of Utah Moran Eye Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Virginia Pediatric Eye Center
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
IWK Health Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3K 6R8
Country
Canada
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
CHU - Sainte-Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
http://www.pedig.net
Description
PEDIG Public Website

Learn more about this trial

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

We'll reach out to this number within 24 hrs