Intravitreal Ranibizumab Injection for Aggressive Versus Type 1 Prethreshold Retinopathy of Prematurity

NCT05701124 | Completed Phase 3 FDA Drug

• 1 other identifier: ZU-IRB#6269/22-7-2020
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Despite advances in the neonatal intensive care units, retinopathy of prematurity (ROP) has become a common reason for blindness and visual disabilities in premature infants so that it accounts for about 5% and 30% of such complications in developed and developing countries. The pathophysiology of ROP is multifactorial. Supplemental oxygen demand and lower gestational age (GA) and birth weight (BW) are among the major risk factors for the occurrence and progression of ROP. Anti-vascular endothelial growth factor (anti-VEGF) agents are a promising modality of treatment for ROP, as laser therapy is associated with disadvantages such as complications from undertreatment or overtreatment, anterior segment burns, hemorrhage, or ischemia, and potentially higher rates of myopia. Ranibizumab is the first approved anti-VEGF treatment for the management of retinopathy, and is a promising alternative to laser therapy. Ranibizumab is a humanized monoclonal recombinant antibody fragment with a shorter half-life and less systemic toxicity than bevacizumab. Its binding affinity is nearly tenfold that of bevacizumab. The plasma half-life of bevacizumab is 17-21 days, while that of ranibizumab is 3 days. Greater systemic absorption of bevacizumab is thought to lead to greater systemic suppression of VEGF. These data may explain the better safety profile of ranibizumab. Type I ROP is defined as any stage of ROP with plus disease in zone I, stage 3 ROP in zone I and stage 2 or 3 ROP with plus disease in zone II . The hallmark of Aggressive-ROP (previously known as Aggressive posterior-ROP) is rapid development of pathological neovascularization and severe plus disease without progression being observed through the typical stages of ROP. It may occur in larger preterm infants and beyond the posterior retina. The aim of this prospective study is to compare the efficacy of intravitreal ranibizumab for type 1 ROP and A-ROP as regard acute ROP regression, recurrence profile, peripheral retinal vascularization and the need for further ablative therapy.

Conditions

Retina Disease; Retinopathy of Prematurity; Ranibizumab

Keywords

Aggressive ROP; Ranibizumab; Type 1 ROP; anti-VEGF; Laser photocoagulation

Outcome Measures

Primary Outcomes (2)

• Number of eyes that achieved regression of plus disease or active neovessels achieved either by single or multiple injections

  active ROP regression

  at 55 weeks post-menstrual age

• The number of eyes in which retinal vessels reach ora serrata (complete retinal vascularization)

  complete retinal vascularization(retinal vessels reach ora serrata)

  at 55 weeks post-menstrual age

Secondary Outcomes (3)

• The number of eyes that showed recurrent plus disease, recurrent neovascularization, reformation of a ridge

  at 55 weeks post-menstrual age

• The number of eyes that needed late peripheral laser

  at 55 weeks post-menstrual age

• The number of eyes progressing to stage 4 or 5 necessitating vitrectomy with/without lensectomy

  one year

Study Arms (2)

Aggressive ROP

ACTIVE COMPARATOR

Intravitreal injection (IVI) was performed under topical anesthesia in standard ophthalmic operating room. 5% povidone-iodine disinfection and topical antibiotic were instilled. Ranibizumab (0.25 mg/0.025 mL) was injected into the vitreous cavity with a 31-gauge needle, aiming the needle directly toward the optic nerve in direction of visual axis 1.0 mm posterior to the corneoscleral junction at the inferotemporal quadrant.

Drug: Ranibizumab (0.25 mg/0.025 mL)

Type 1 prethreshold ROP

ACTIVE COMPARATOR

Intravitreal injection (IVI) was performed under topical anesthesia in standard ophthalmic operating room. 5% povidone-iodine disinfection and topical antibiotic were instilled. Ranibizumab (0.25 mg/0.025 mL) was injected into the vitreous cavity with a 31-gauge needle, aiming the needle directly toward the optic nerve in direction of visual axis 1.0 mm posterior to the corneoscleral junction at the inferotemporal quadrant.

Drug: Ranibizumab (0.25 mg/0.025 mL)

Interventions

Ranibizumab (0.25 mg/0.025 mL) DRUG

Intravitreal injection (IVI) was performed under topical anesthesia in standard ophthalmic operating room. 5% povidone-iodine disinfection and topical antibiotic were instilled. Ranibizumab (0.25 mg/0.025 mL) was injected into the vitreous cavity with a 31-gauge needle, aiming the needle directly toward the optic nerve in direction of visual axis 1.0 mm posterior to the corneoscleral junction at the inferotemporal quadrant. The intraocular pressure and central artery perfusion were then checked.

Also known as: Lucentis

Aggressive ROP; Type 1 prethreshold ROP

Eligibility Criteria

• Age: 28 Days - 3 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants with a birth weight of ≤ 1500 g or gestational age of ≤ 30 weeks and selected infants with birth weight between 1500 and 2000 g or gestational age of more than 30 weeks with an unstable clinical course, including those requiring cardiorespiratory support.
• Infants with type 1 ROP, as defined by the ETROP study 11, Zone 1, any stage ROP with plus disease; Zone 1, stage 3 ROP with or without plus disease; Zone 2, stage 2 or 3 ROP with plus disease( affecting either one or both eyes).
• Aggressive ROP (A-ROP), according to the International Classification of ROP (ICROP) criteria affecting either one or both eyes.

You may not qualify if:

• Eyes with previous intravitreal injections.
• Eyes with previous laser therapy.
• Eyes with any other pathology, other than ROP.
• Eyes with ROP stage 4 or 5.

Sponsors & Collaborators

• Zagazig University: lead
• Cairo University: collaborator

Study Sites (1)

Zagazig University, Faculty of medicine

Zagazig, 44511, Egypt

Location

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sherif Abbas Dabour, MD, FRCS

  Zagazig University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: single masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Study Record Dates

• First Submitted: January 8, 2023
• First Posted: January 27, 2023
• Study Start: November 20, 2020
• Primary Completion: November 20, 2022
• Study Completion: November 20, 2022
• Last Updated: January 30, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)