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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04634604
Recruitment Status : Recruiting
First Posted : November 18, 2020
Last Update Posted : November 8, 2021
Sponsor:
Collaborators:
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Information provided by (Responsible Party):
Jaeb Center for Health Research

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.


Condition or disease Intervention/treatment Phase
Retinopathy of Prematurity Drug: Bevacizumab Procedure: Laser Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 212 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Trial of Low-Dose Bevacizumab Versus Laser for Type 1 Retinopathy of Prematurity
Estimated Study Start Date : November 2021
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : April 2029

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

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 Name: Avastin




Primary Outcome Measures :
  1. Treatment Success Rate At 6 Months Adjusted Age [ Time Frame: 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).



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Ages Eligible for Study:   up to 6 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04634604


Contacts
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Contact: Raymond T Kraker, MSPH 8139758690 rkraker@jaeb.org
Contact: Brooke P Fimbel 813-975-8690 bfimbel@jaeb.org

Locations
Show Show 35 study locations
Sponsors and Collaborators
Jaeb Center for Health Research
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Investigators
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Study Chair: David K Wallace, MD, MPH Indiana University
  Study Documents (Full-Text)

Documents provided by Jaeb Center for Health Research:
Study Protocol  [PDF] August 26, 2021
Statistical Analysis Plan  [PDF] October 5, 2021
Informed Consent Form  [PDF] June 25, 2021

Additional Information:
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Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT04634604    
Other Study ID Numbers: ROP3
UG1EY011751 ( U.S. NIH Grant/Contract )
First Posted: November 18, 2020    Key Record Dates
Last Update Posted: November 8, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Retinal Diseases
Retinopathy of Prematurity
Premature Birth
Eye Diseases
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Infant, Premature, Diseases
Infant, Newborn, Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors