Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05701124 |
| Other study ID # |
ZU-IRB#6269/22-7-2020 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
November 20, 2020 |
| Est. completion date |
November 20, 2022 |
Study information
| Verified date |
January 2023 |
| Source |
Zagazig University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
