PROPranolol eye DROPs in newborns with retinopathy of prematurity (DROP-PROP)
| ISRCTN | ISRCTN68126628 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68126628 |
| EudraCT/CTIS number | 2013-002062-39 |
| ClinicalTrials.gov number | NCT02014454 |
| Secondary identifying numbers | N/A |
- Submission date
- 16/01/2014
- Registration date
- 27/03/2014
- Last edited
- 30/01/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Eye Diseases
Plain English summary of protocol
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
Contact information
Scientific
Neonatal Intensive Care Unit
A. Meyer University Childrens' Hospital
Viale Pieraccini 24
Florence
50139
Italy
| Phone | +39 (0)55 5662434 |
|---|---|
| l.filippi@meyer.it |
Study information
| Study design | Interventional open-label phase 2 multicenter study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Safety and efficacy of PROPranolol eye DROPs in newborns with retinopathy of prematurity (DROP-PROP) |
| Study acronym | DROP-PROP |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/11/2013 |
| Completion date | 01/11/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Both |
| Target number of participants | 55 preterm newborns |
| Key inclusion criteria | 1. Preterm newborns (gestational age 23-32 weeks) with stage 2 ROP, zone II without plus 2. A signed parental informed consent |
| Key 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 |
| Date of first enrolment | 01/11/2013 |
| Date of final enrolment | 01/11/2015 |
Locations
Countries of recruitment
- Italy
Study participating centre
50139
Italy
Sponsor information
Hospital/treatment centre
Neonatal Intensive Care Unit
Viale Pieraccini 24
Florence
50139
Italy
| Phone | +39 (0)55 5662434 |
|---|---|
| direzioneamministrativa@meyer.it | |
"ROR" |
https://ror.org/01n2xwm51 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/02/2017 | Yes | No |
Editorial Notes
30/01/2017: Publication reference added.
