Safety and Efficacy of Propranolol in Newborns With Retinopathy of Prematurity

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether the administration of propranolol is effective in the treatment of the retinopathy of the prematurity.

Detailed Description
-----------------
Retinopathy of Prematurity (ROP) is still a major cause of blindness in children in developed countries around the world, and an increasing cause of blindness in developing countries. The ablation of the retina with photocoagulation by laser or cryotherapy reduces the incidence of blindness by suppressing the neovascular phase of ROP. However, the visual outcomes after treatment are often poor. 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. The purpose of this study is to evaluate whether the administration of propranolol is safe and is able to reduce the incidence of blindness by suppressing the neovascular phase of ROP compared to a control group receiving conventional laser therapy.

Official Title
-----------------
Safety and Efficacy of Treatment With Propranolol in Newborns With Retinopathy of Prematurity: a Pilot Study

Conditions
-----------------
Retinopathy of Prematurity

Intervention / Treatment
-----------------
* Drug: Propranolol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants who have been screened for ROP (≤ 32 weeks gestation) who develop Stage 2 ROP in zone II without plus. Informed Consent from a parent Exclusion Criteria: Newborns with one or more of the following conditions at the enrollment in the study: Heart failure. Recurrent episodes of bradycardia (Heart rate less than 90 bpm). Atrio-ventricular block (second or third degree). Significant congenital heart anomaly, not including patent ductus arteriosus, patent foramen ovale or small ventricular septal defect. Hypotension. Renal failure. Cerebral hemorrhage. Other diseases which contraindicate the use of beta-blockers Newborns with ROP stages more advances than Stage 2 in zone II without plus. Informed Consent from a parent refused. This will mean that an infant automatically will receive standard laser therapy. No data will be used from an infant without Informed Consent.

Ages Eligible for Study
-----------------
Minimum Age: 22 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propranolol<br>Oral Propranolol administration is the experimental arm of this study | Drug: Propranolol<br>* Dosage of 0.5mg/Kg oral, every 6 hours. 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 such events occur in any of the 3 groups of gestational age, the study could start again with half dose (0.25mg/Kg oral, every 6 hours) after notification to the Ethics Committee. 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).<br>|
| No Intervention: Control<br>Control arm is treated following the standard treatment schedule of Early Treatment For Retinopathy Of Prematurity Cooperative Group | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary aim is to evaluate the safety of propranolol administration |  | Three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary aim is to evaluate the efficacy of treatment with propranolol for reducing blindness and retinal detachment in newborns with ROP |  | six months from the beginning of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Newborn, Retinal Diseases, Angiogenesis Modulating Agents, Adrenergic beta-Antagonists