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Ranibizumab Vs Bevacizumab for Type 1 Retinopathy of Prematurity

Phase 3
Conditions
Retinopathy of Prematurity Both Eyes
Interventions
Drug: Bevacizumab, Ranibizumab
Registration Number
NCT05033106
Lead Sponsor
Zagazig University
Brief Summary

Retinopathy of prematurity (ROP) with inadequate growth and development of retinal blood vessels in premature infants is one of the foremost reasons for childhood blindness. Recently there is a shift of treatment to VEGF inhibitors which can regress ROP without destroying the peripheral retina. Yet, the best drug has not been identified.Bevacizumab is a larger, full-length immunoglobulin G (IgG) molecule with slower retinal clearance and therefore prolonged diffusion into the systemic circulation, up to 3 weeks. In contrast, the systemic half-life of a Fab molecule, such as ranibizumab, is a few hours. The objective is to compare the efficacy and reliability of intravitreal bevacizumab with standard 0.625 mg dose and intravitreal ranibizumab treatments for type 1 ROP, namely pattern of disease regression, recurrence of ROP, necessity of subsequent ablative procedures.

Detailed Description

Objectives

To compare the efficacy and reliability of intravitreal bevacizumab with standard 0.625 mg dose and intravitreal ranibizumab treatments for type 1 ROP, namely pattern of disease regression, recurrence of ROP, necessity of subsequent ablative procedures.

Study population \& Sample size Infants with Type 1 ROP (affecting both eyes) screened at neonatal intensive care unit (NICU) of Cairo University.

The sample size is calculated to be 36 eyes of 18 infants using open Epi confidence total 95%, power of the study 80% according to the following : the mean SD of axial length of patients with stage 3 ROP using bevacizumab versus ranibizumab (20.3 1.16 versus 19.4 ).

Study Design

This is a prospective, comparative, interventional non inferiority study.

Methods

* Infants with type 1 ROP affecting both eyes will be included.

* Before intravitreal injection, the parents or legal guardian of the infants will be informed about the procedure.

* After written consent is obtained, the pupil will be dilated with 2.5% phenylephrine and 0.5% tropicamide injection.

* The injections will be performed in the operating theatre under general (light inhalational anesthesia) or topical anesthesia with Benoxinate hydrochloride 0.4%.

* Povidone iodine10% swab will be applied on the eyelids and eyelashes. A sterile eyelid speculum will be inserted. Each eye will be meticulously bathed with 5% povidone iodine solution for 3 min before intravitreal injection.

* A dose of 0.25 mg/0.025 mL ranibizumab (Lucentis) is injected in the right eye of the infant and 0.625 mg/0.025 mL bevacizumab is injected into the vitreous cavity of the left eye 1 mm posterior to the superior/inferior temporal limbus via 30 G needle. The two injections are done sequentially on two consecutive days starting with the eye of more advanced disease.

* Fundus examination will be conducted with an indirect ophthalmoscope and a 28-D lens. The central retinal artery and the lens will be evaluated in addition to whether a retinal tear is present.

* Postoperative moxifloxacin 0.4% drops will be prescribed 4 times daily for one week.

* Patients will be seen 24 hours after first injection, to monitor for any signs of infection.

* Infants will then be seen weekly for 4 weeks and dilated fundus examination and and digital coloured fundus images by RetCam will be performed to document response of the disease.

* Success criteria to the IVB injection will be defined as, during the follow up period of 60 weeks' postmenstrual age:

* recovery of the plus disease

* regression of any stage of ROP

* progression of peripheral retinal vascularization

* If any progression occurs in the disease course, in terms of: increase in plus disease or progression to higher stage of ROP, immediate second IVB dose 0.625mg will be given to either groups.

* Follow-up will be continued for a minimum of one year corrected age or until we ensure complete peripheral retinal vascularization.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
36
Inclusion Criteria
  • Infants with a birth weight of ≤ 1500 g or geststional 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. Patients with bilateral disease who will receive bilateral injections, are only included. Type 1 ROP according to ETROP study which is defined as, Zone I ROP with plus disease, Zone I, stage 3 ROP without plus disease and Zone II, stage 2 or 3 ROP with plus disease.
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. Eyes with mucopurulent or purulent conjunctivitis. Infants who will not be able to comply to the follow-up schedule.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Eyes with IVI bevacizumabBevacizumab, Ranibizumab0.625 mg/0.025 mL bevacizumab is injected into the vitreous cavity of the left eye
Eyes with IVI ranibizumabBevacizumab, RanibizumabA dose of 0.25 mg/0.025 mL ranibizumab (Lucentis) is injected in the right eye of the infant
Primary Outcome Measures
NameTimeMethod
• Regression achieved either by single injection or multiple injections or additional laser therapy at 60 weeks postmenstrual age.60 weeks PMA

regression of plus disease and the active neovessels

Secondary Outcome Measures
NameTimeMethod
• Recurrence of ROP60 weeks PMA

(recurrent plus disease, recurrent neovascularization, or reformation of ridge despite treatment)

Trial Locations

Locations (1)

Zagazig University

🇪🇬

Zagazig, Egypt

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