a Prospective Cohort Study for Propranolol Treatment in Retinopathy of Prematurity

Guangdong Women and Children Hospital

Status and phase: Unknown; Phase 2

Conditions: Retinopathy of Prematurity

Treatments: Drug: Propranolol; Drug: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03038295

lqiong

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and efficacy of oral/local propranolol in preterm newborns who diagnosed as early phase of retinopathy of prematurity (ROP).

Full description

The incidence of Retinopathy of Prematurity (ROP) in preterm newborns less than 1500g is about 60% in the developed countries around the world, while there are much more preterm newborns more than 1500g and 32 weeks gestational age with Retinopathy of Prematurity (ROP) had to be treated in the developing countries. ROP has listed top of the five causes lead to blindness in children, which seriously threated children's vision and quality of life.

The ablation of the retina with photocoagulation by laser or cryotherapy reduces the incidence of blindness by suppressing the neovascular phase of ROP. However, those Surgeries require anesthesia and some of them may result in complications such as apnea, neonatal necrotizing enterocolitis, sepsis, and hemorrhage of digestive tract. As a result, it's important to study an alternative non-surgical treatment method.

The development of ROP depends largely from vascular endothelial growth factor (VEGF). The reduction of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP.

Propranolol is a kind of beta-adrenergic receptor (β-AR) which can inhibit the expression of VEGF and has been first choice of treating infantile hemangioma, the most common tumor of infancy. There are some pilot studies suggesting that the administration of oral propranolol is effective in counteracting the progression of ROP in patients without operation indication. Nevertheless that safety is a concern, for oral propranolol may result in associated complications and side effects such as bradycardia, hypotension, injury of cerebrum growth and olfactory.

Recently a research of eye drop propranolol in a mouse model of oxygen-induced retinopathy (OIR) has shown that propranolol was still effective in inhibiting angiogenic processes, indicating that local administration is equally effective.

The purpose of this study is to evaluate safety and efficacy of oral/local propranolol in preterm newborns with early phase of retinopathy of prematurity (ROP).The study will be followed up for a period of time, observing the development of optic and nerve system complications to further confirm the efficacy of propranolol to ROP treatment, which can provide theoretical basis for the futher clinical application of the drug in ROP.

Enrollment: 100 estimated patients

Sex: All

Ages: Under 8 weeks old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Preterm newborns (birth weight less than 1500g) with stage 1/2 ROP in Zone 2 or 3 without plus
• A signed parental informed consent

Exclusion criteria

• Newborns with heart failure
• Newborns with recurrent bradycardia (heart rate < 90 beat per minute)
• Newborns with second or third degree atrioventricular block
• Newborns with congenital cardiovascular anomalies, except for persistent ductus arteriosus, patent foramen ovale and small ventricular septal defects
• Newborns with hypotension
• Newborns with renal failure
• Newborns with actual cerebral haemorrhage
• Newborns with other diseases which contraindicate the use of beta-adrenoreceptor blockers.
• Newborns with a more severe stage of ROP than stage 2 or in Zone 1

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 4 patient groups, including a placebo group

oral propranol group

Experimental group

Description:

Enrolled preterm newborns will receive oral propranolol 0.25mg/kg daily(every 24 hours). The treatment will be started as soon as the diagnosis of stage 1 or 2 ROP without plus is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days.

Treatment:

Drug: Propranolol

oral placebo group

Placebo Comparator group

Description:

Enrolled preterm newborns will receive oral normal saline 0.25mg/kg daily(every 24 hours) and other disposals will be done similarily to the oral propranol group.

Treatment:

Drug: placebo

eye drop propranol group

Experimental group

Description:

Enrolled preterm newborns will receive propranolol as ophthalmic solution (0.2%). 3 microdrops of 6 microliters (μL) propranolol solution (= 6 μg propranolol/microdrop) will be topically applied with a calibrated pipette,in each eye, four times daily (every 6 hours) . The treatment will be started as soon as the diagnosis of stage 1 or 2 ROP without plus is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days.

Treatment:

Drug: Propranolol

eye drop placebo group

Placebo Comparator group

Description:

Enrolled preterm newborns will receive placebo as ophthalmic solution in the same way of eye drop propranolol and other disposals will be done similarily to the eye drop propranol group.

Treatment:

Drug: placebo