Clinical trial NCT02014454: Safety and Efficacy of Propranolol Eye Drops in Treating Retinopathy of Premature
Official title: Safety and Efficacy of Propranolol Eye Drops in Newborns With Retinopathy of Premature (DROP-PROP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Retinopathy of Prematurity
Keywords: Retinopathy of prematurity
Propranolol
Eye drops
Newborns
Retinal angiogenesis
Retinal neovascularization
Lead sponsor: Meyer Children's Hospital IRCCS
Sponsor class: OTHER
First posted: 2013-12-18
Enrollment: 23
Sex: ALL
Minimum age (years): 1
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 retinopathy of prematurity (ROP). Preterm newborns (gestational age 23-32 weeks) with a stage 2 ROP (zone II without plus) will receive propranolol eye drops treatment until retinal vascularization will be completed.

Propranolol concentrations will be measured on dried blood spots during the first 3 days of treatment and at the steady state. 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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Incidence rate of progression from stage 2 ROP to more severe stage ROP (stage 2 or 3 with plus, stage 4 and stage 5)
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Plasma concentrations of propranolol at the steady state
timeFrame: 10th day of treatment
Secondary outcomes:
measure: Number of newborns who progress to Stage 3 without plus ROP
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Number of newborns who progress to Stage 4 or 5 ROP with total or partial retinal detachment
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Number of newborns who need laser treatment
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Number of newborns who need rescue treatment with bevacizumab
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Number of newborns who need vitrectomy
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Collection of adverse events due to eye drop propranolol treatment
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
Other outcomes:
Locations:
city: Florence
country: Italy
facility: Neonatal Intensive Care Unit, A. Meyer University Childrens' Hospital
city: Milan
country: Italy
facility: Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan
Study officials:
affiliation: Meyer Children's Hospital IRCCS
name: Luca Filippi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. Epub 2013 Sep 18.
citation: 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. Epub 2013 Mar 23.
citation: Filippi L, Cavallaro G, Fiorini P, Malvagia S, Della Bona ML, Giocaliere E, Bagnoli P, Dal Monte M, Mosca F, Donzelli G, la Marca G. Propranolol concentrations after oral administration in term and preterm neonates. J Matern Fetal Neonatal Med. 2013 May;26(8):833-40. doi: 10.3109/14767058.2012.755169. Epub 2013 Jan 31.
citation: Della Bona ML, Malvagia S, Villanelli F, Giocaliere E, Ombrone D, Funghini S, Filippi L, Cavallaro G, Bagnoli P, Guerrini R, la Marca G. A rapid liquid chromatography tandem mass spectrometry-based method for measuring propranolol on dried blood spots. J Pharm Biomed Anal. 2013 May 5;78-79:34-8. doi: 10.1016/j.jpba.2013.01.034. Epub 2013 Feb 4.
citation: Filippi L, Cavallaro G, Bagnoli P, Dal Monte M, Fiorini P, Berti E, Padrini L, Donzelli G, Araimo G, Cristofori G, Fumagalli M, la Marca G, Della Bona ML, Pasqualetti R, Fortunato P, Osnaghi S, Tomasini B, Vanni M, Calvani AM, Milani S, Cortinovis I, Pugi A, Agosti M, Mosca F. Propranolol 0.1% eye micro-drops in newborns with retinopathy of prematurity: a pilot clinical trial. Pediatr Res. 2017 Feb;81(2):307-314. doi: 10.1038/pr.2016.230. Epub 2016 Nov 4.