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

NCT ID: NCT05701124

Last Updated: 2023-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-20
• Study Completion Date: 2022-11-20

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.

Detailed Description

A prospective randomized study of 37 eyes of 30 infants, who received intravitreal injections of ranibizumab in one eye (the most severe) or both eyes, were included. A-ROP group included 18 eyes of 15 infants and type 1 ROP group included 19 eyes of 15 infants. The primary outcome measure was the number of eyes that achieved regression of ROP without additional treatment till 55 weeks' post-menstrual age (PMA). The mean follow-up period for A-ROP group was 11.44 months and 13.95 months for type 1 ROP group.

Treatment was performed within 72 hours once treatment criteria were detected. 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. Topical antibiotics were given for 7 days postoperatively. All infants were followed up on the next day, third day, then weekly until the regression of ROP, after that every (2-4) weeks until a minimum of 55 weeks' post menstrual age (PMA) or retinal vascularization achieved zone III without an active component such as hemorrhage or exudation or clinically significant tractional elements, which came earlier. Each examination evaluated disease regression (via indirect fundoscopic analysis), recurrence, the presence of tractional elements and peripheral vascularization. Then follow up was continued monthly for at least 6 months following treatment.

Successful treatment was defined as remission of plus disease, good pupil dilation and reduced disease grade. Outcomes were further classified as insufficient regression (persistence of plus disease and neovascularization at 3-5 days' post-injection), progression (post-injection intravitreal hemorrhage, increased neovascularization and formation of tractional components) and recurrence requiring treatment (recurrence of plus disease, recurrent neovascularization, reformation of a ridge or extraretinal fibrovascular proliferation, despite initial regression post injection) Once insufficient regression or ROP recurrence requiring treatment was determined, rescue therapy of IVR was applied.

Cases with no recurrence or recurrence not requiring treatment (stage 1 or 2 eyes, with Zone 2 or Zone 3 localisation, not accompanied by plus disease) were closely monitored until peripheral retinal vascularization was completed.

In case of failed peripheral retinal vascularization to approach zone III until 55 weeks' PMA, an indirect infrared diode laser (IRIDEX, Iris Medical SL laser with laser indirect ophthalmoscope (LIO) Ophthalmic Laser, 810 nm, USA) was used to apply photocoagulation through a +20/+28 diopter condensing lens under sedation or general anesthesia in the operating room to reduce the risk of late ROP reactivation.

Follow-up examinations were made weekly for the first month after laser photocoagulation and at 3-4-week intervals thereafter until the ROP findings receded. Follow-up examinations were continued at 3-4-month intervals after the patients turned 1-year old.

Conditions

Retina Disease; Retinopathy of Prematurity; Ranibizumab

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Aggressive ROP

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.

Group Type: ACTIVE_COMPARATOR

Ranibizumab (0.25 mg/0.025 mL)

Intervention Type: 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.

Type 1 prethreshold ROP

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.

Group Type: ACTIVE_COMPARATOR

Ranibizumab (0.25 mg/0.025 mL)

Intervention Type: 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.

Interventions

Ranibizumab (0.25 mg/0.025 mL)

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.

Intervention Type: DRUG

Other Intervention Names

Lucentis

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 28 Days
• Maximum Eligible Age: 3 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: collaborator

Zagazig University

OTHER_GOV

Sponsor Role: lead

Responsible Party

Ghada Mahmoud Tawfik Ibrahim Eladawy

principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sherif Abbas Dabour, MD, FRCS

Role: STUDY_DIRECTOR

Zagazig University

Locations

Zagazig University, Faculty of medicine

Zagazig, , Egypt

Countries

Egypt

Other Identifiers

ZU-IRB#6269/22-7-2020

Identifier Type: -

Identifier Source: org_study_id