ISRCTN - ISRCTN68126628: PROPranolol eye DROPs in newborns with retinopathy of prematurity (DROP-PROP)

Plain English Summary

Background and study aims
A previous study has shown that oral propranolol is effective in preventing the progression of a disease of the eye called retinopathy of prematurity (ROP) in preterm newborns, but its safety is not sufficient. Therefore we have developed a topical delivery system and the aim of the present study is to evaluate the safety and efficacy of propranolol eye drops in preterm newborns with a precocious stage of ROP.

Who can participate?
Preterm newborns (gestational Age 23-32 weeks) with a stage 2 ROP (zone II without plus) who are admitted to the neonatal care units contributing to the study (Neonatal Intensive Care Unit, A. Meyer University Childrens Hospital of Florence and Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan) will be considered for enrolment.

What does the study involve?
All the enrolled newborns will receive propranolol. It will be applied in each eye, three times daily (every 8 hours). The treatment will continue until the complete development of retinal vascularization, but no more than 60 days.

What are the possible benefits and risks of participating?
Eye drops propranolol is considered to be effective in counteracting the progression of ROP if the treatment decreases the rate of progression from stage 2 ROP to more severe stage ROP (stage 2 or 3 with plus) from actual 38% to 19% or less. Additionally, in order to verify the treatment safety, the propranolol concentrations will be measured on dried blood spots at the steady state (10th day). The main risk of receiving eye drops propranolol is represented by the development of adverse events (i.e. bradycardia, bronchospasm, severe hypotension), similar to those occurring after oral administration. Therefore cardiovascular and respiratory parameters will be continuously monitored and blood samplings checking metabolic, renal and liver functions, as well as the evaluation of cardiac function, will be periodically performed.

Where is the study run from?
Neonatal Intensive Care Unit, A. Meyer University Childrens Hospital of Florence and Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan (Italy)

When is the study starting and how long is it expected to run for?
The overall duration of the study will be 2 years, with the goal of enrolling 55 preterm newborns.

Who is funding the study?
A. Meyer University Children's Hospital (Italy)

Who is the main contact?
Luca Filippi
l.filippi@meyer.it

Trial website

Contact information

Type

Scientific

Primary contact

Dr Luca Filippi

ORCID ID

Contact details

Neonatal Intensive Care Unit
A. Meyer University Childrens' Hospital
Viale Pieraccini 24
Florence
50139
Italy
+39 (0)55 5662434
l.filippi@meyer.it

Additional identifiers

EudraCT number

2013-002062-39

ClinicalTrials.gov number

NCT02014454

Protocol/serial number

N/A

Study information

Scientific title

Safety and efficacy of PROPranolol eye DROPs in newborns with retinopathy of prematurity (DROP-PROP)

Acronym

DROP-PROP

Study hypothesis

We have recently verified that oral propranolol is effective in preventing retinopathy of prematurity (ROP) progression in preterm newborns, but the safety of systemic administration is not adequate. In order to decrease the plasma propranolol concentrations and the adverse events, we have developed a topical delivery system. The aim of the present study is to evaluate the safety and efficacy of propranolol eye drops in preterm newborns with a precocious stage of ROP.

Ethics approval

Pediatric Regional Ethics Committee (Comitato Etico Pediatrico Regionale) affiliated to Pediatric Ethics Committee of the Region of Tuscany (Comitato Etico Pediatrico Regionale/Regione Toscana), 24/07/2013

Study design

Interventional open-label phase 2 multicenter study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Retinopathy of prematurity

Intervention

All the enrolled preterm newborns will receive propranolol as ophthalmic solution (0.1%): 3 microdrops of 6 μL propranolol solution (= 6 μg propranolol/microdrop) will be topically applied with a calibrated pipette, in each eye, three times daily (every 8 hours).The treatment will continue until the complete development of retinal vascularization, but no more than 60 days. The propranolol treatment will be always associated to the conventional approach adopted by the ETROP Cooperative Group.

Intervention type

Drug

Phase

Not Specified

Drug names

Propranolol

Primary outcome measure

1. Incidence rate of progression from stage 2 ROP to more severe stage ROP (stage 2 or 3 with plus, stage 4 and stage 5), evaluated by ophthalmologic examinations at baseline and at least weekly, until the resolution of ROP
2. Plasma concentrations of propranolol at the steady state, measured on the 10th day of treatment by dried blood spots

Secondary outcome measures

1. Number of newborns who progress to Stage 3 without plus ROP
2. Number of newborns who progress to Stage 4 or 5 ROP with total or partial retinal detachment
3. Number of newborns who need laser treatment
4. Number of newborns who need rescue treatment with bevacizumab
5. Number of newborns who need vitrectomy
6. Collection of adverse events due to eye drop propranolol treatment

Secondary outcomes will be evaluated by ophthalmologic examinations at baseline and at least weekly, until the resolution of ROP.

Overall trial start date

01/11/2013

Overall trial end date

01/11/2015

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Preterm newborns (gestational age 23-32 weeks) with stage 2 ROP, zone II without plus
2. A signed parental informed consent

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

55 preterm newborns

Participant exclusion criteria

1. Newborns with heart failure
2. Newborns with congenital cardiovascular anomalies, except for persistent ductus arteriosus, patent foramen ovale and small ventricular septal defects
3. Newborns with recurrent bradycardia (heart rate < 90 beat per minute)
4. Newborns with second or third degree atrioventricular block
5. Newborns with hypotension
6. Newborns with renal failure
7. Newborns with actual cerebral haemorrhage
8. Newborns with other diseases which contraindicate the use of beta-adrenoreceptor blockers

Recruitment start date

01/11/2013

Recruitment end date

01/11/2015

Locations

Countries of recruitment

Italy

Trial participating centre

A. Meyer University Childrens' Hospital
Florence
50139
Italy

Sponsor information

Organisation

A. Meyer University Children's Hospital (Italy)

Sponsor details

Neonatal Intensive Care Unit
Viale Pieraccini 24
Florence
50139
Italy
+39 (0)55 5662434
direzioneamministrativa@meyer.it