Clinical trial NCT03038295: a Prospective Cohort Study for Propranolol Treatment in Retinopathy of Prematurity
Official title: Safety and Efficacy of Propranolol Treatment in Newborns With Retinopathy of Prematurity:a Prospective Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Retinopathy of Prematurity
Keywords: Retinopathy of Prematurity
propranolol
ROP
Lead sponsor: Guangdong Women and Children Hospital
Sponsor class: OTHER
First posted: 2017-01-31
Enrollment: 100
Sex: ALL
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of newborns who have ROP progression
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Number of newborns who need surgical treatment
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Number of newborns who have side effects
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Plasma concentrations of propranolol at the steady state measured by dried blood spots
timeFrame: 10th day of treatment
Secondary outcomes:
measure: visual assessment of enrolled newborns
timeFrame: about 12 months
measure: Scores of Gesell development scale of enrolled newborns
timeFrame: about 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Guangdong Women and Children Hospital
name: Chuan Nie, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zin A, Gole GA. Retinopathy of prematurity-incidence today. Clin Perinatol. 2013 Jun;40(2):185-200. doi: 10.1016/j.clp.2013.02.001.
citation: Fierson WM; American Academy of Pediatrics Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; American Association of Certified Orthoptists. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2013 Jan;131(1):189-95. doi: 10.1542/peds.2012-2996. Epub 2012 Dec 31.
citation: Filippi L, Cavallaro G, Bagnoli P, Dal Monte M, Fiorini P, Donzelli G, Tinelli F, Araimo G, Cristofori G, la Marca G, Della Bona ML, La Torre A, Fortunato P, Furlanetto S, Osnaghi S, Mosca F. Oral propranolol for retinopathy of prematurity: risks, safety concerns, and perspectives. J Pediatr. 2013 Dec;163(6):1570-1577.e6. doi: 10.1016/j.jpeds.2013.07.049. Epub 2013 Sep 18.
citation: Dal Monte M, Casini G, la Marca G, Isacchi B, Filippi L, Bagnoli P. Eye drop propranolol administration promotes the recovery of oxygen-induced retinopathy in mice. Exp Eye Res. 2013 Jun;111:27-35. doi: 10.1016/j.exer.2013.03.013. Epub 2013 Mar 23.