Safety and Efficacy of Propranolol 0.2% Eye Drops in Treating Retinopathy of Premature: A Pilot Study (DROP-ROP-0.2%)

Study Overview
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Brief Summary
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The aim of the present study is to evaluate the safety and efficacy of propranolol 0.2% eye drops in treating preterm newborns with a precocious stage of retinopathy of prematurity (ROP). Preterm newborns (gestational age 23-32 weeks) with a stage 1 ROP will receive propranolol 0.2% eye drops treatment until retinal vascularization will be completed, but no more than 90 days. Propranolol concentrations will be measured on dried blood spots at the steady state (10th day). Cardiovascular and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions will be performed periodically, as well as cardiac function, in order to verify the treatment safety. Serial ophthalmological evaluations will be planned to monitor the efficacy of the treatment, the ROP progression and the possible complications.

Official Title
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Safety and Efficacy of Propranolol 0.2% Eye Drops in Treating Newborn With Retinopathy of Premature: A Pilot Study (DROP-ROP-0.2%)

Conditions
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Retinopathy of Prematurity

Intervention / Treatment
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* Drug: Propranolol 0.2% eye drops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm newborns (gestational age 23-32 weeks) with stage 1 ROP 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 1
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propranolol 0.2% eye drops<br>Enrolled preterm newborns will receive propranolol as ophthalmic solution (0.2%). The treatment will be started as soon as the diagnosis of stage 1 ROP is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days. Cardiovascular and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions will be performed periodically, as well as cardiac function, in order to verify the treatment safety. Propranolol concentrations will be measured on dried blood spots at the steady state (10th day). Serial ophthalmological evaluations will be planned to monitor the efficacy of the treatment, the ROP progression and the possible complications. | Drug: Propranolol 0.2% eye drops<br>* 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). Propranolol treatment will be always associated to the conventional approach adopted by the Early Treatment for Retinopathy of Prematurity Study (ETROP) Cooperative Group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of progression from stage 1 ROP to zone II stage 2 ROP with plus |  | participants will be followed for the duration of hospital stay, an expected average of 2 months | 
| Incidence rate of progression from stage 1 ROP to zone II stage 3 ROP with plus |  | participants will be followed for the duration of hospital stay, an expected average of 2 months | 
| Plasma concentrations of propranolol at the steady state measured by dried blood spots |  | 10th day of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of newborns who progress to Stage 2 without plus ROP |  | participants will be followed for the duration of hospital stay, an expected average of 2 months | 
| Number of newborns who progress to Stage 3 without plus ROP |  | participants will be followed for the duration of hospital stay, an expected average of 2 months | 
| Number of newborns who progress to Stage 4 with total or partial retinal detachment |  | participants will be followed for the duration of hospital stay, an expected average of 2 months | 
| Number of newborns who progress to Stage 5 ROP with total or partial retinal detachment |  | participants will be followed for the duration of hospital stay, an expected average of 2 months | 
| Number of newborns who need vitrectomy |  | participants will be followed for the duration of hospital stay, an expected average of 2 months | 
| Collection of adverse events due to eye drop propranolol treatment |  | participants will be followed for the duration of hospital stay, an expected average of 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinopathy of prematurity, Propranolol, Newborn, Eye Drops, Retinal angiogenesis, Retinal neovascularization