a Prospective Cohort Study for Propranolol Treatment in Retinopathy of Prematurity

Retinopathy of Prematurity Clinical Trial

Official title:

Safety and Efficacy of Propranolol Treatment in Newborns With Retinopathy of Prematurity:a Prospective Cohort Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03038295
• Other study ID #: lqiong
• Status: Not yet recruiting
• Phase: Phase 2
• First received: January 19, 2017
• Last updated: February 1, 2017
• Start date: March 2017
• Est. completion date: December 2019

Study information

• Verified date: February 2017
• Source: Guangdong Women and Children Hospital
• Contact: Chuan Nie, Doctor
• Phone: +86-136-8227-0294
• Email: chuannie[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 8 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• Propranolol
Oral propranolol:0.25mg/kg daily(every 24 hours);Eye drop propranolol(0.2%):3 microdrops,in each eye, four times daily (every 6 hours) .Both administration routes will be discontinued until retinal vascularization will be completed, but no more than 90 days.The study will be discontinued immediately in the presence of serious adverse effects attributable to the pharmacological actions of propranolol (severe hypotension, bradycardia or bronchospasm).In case of surgery or induction of anesthesia during the administration of propranolol, the drug should be discontinued at least 24 hours before surgery.In cases of severe hypotension or bradycardia may be administered one or more of the following drugs:Atropine.Isoproterenol hydrochloride (isoprenaline).Terlipressin.Glucagon In case of severe bronchospasm may be used salbutamol aerosol or salbutamol + ipratropium bromide. Betamethasone could be used for aerosol or systemic (intravenous or intramuscular).
• placebo
Oral/eye drop placebo will be taken in enrolled newborns. Other treatment will follow the standard treatment schedule of Early Treatment For Retinopathy Of Prematurity Cooperative Group.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong Women and Children Hospital

References & Publications (4)

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. — View 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. Review. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of newborns who have ROP progression		participants will be followed for the duration of hospital stay, an expected average of 2 months
Primary	Number of newborns who need surgical treatment		participants will be followed for the duration of hospital stay, an expected average of 2 months
Primary	Number of newborns who have side effects		participants will be followed for the duration of hospital stay, an expected average of 2 months
Primary	Plasma concentrations of propranolol at the steady state measured by dried blood spots		10th day of treatment
Secondary	visual assessment of enrolled newborns		about 12 months
Secondary	Scores of Gesell development scale of enrolled newborns		about 12 months

External Links

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