Clinical trial NCT02504944: Safety and Efficacy of Propranolol 0.2% Eye Drops in Treating Retinopathy of Premature: A Pilot Study (DROP-ROP-0.2%)
Official title: Safety and Efficacy of Propranolol 0.2% Eye Drops in Treating Newborn With Retinopathy of Premature: A Pilot Study (DROP-ROP-0.2%)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Retinopathy of Prematurity
Keywords: Retinopathy of prematurity
Propranolol
Newborn
Eye Drops
Retinal angiogenesis
Retinal neovascularization
Lead sponsor: Meyer Children's Hospital IRCCS
Sponsor class: OTHER
First posted: 2015-07-22
Enrollment: 98
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence rate of progression from stage 1 ROP to zone II stage 2 ROP with plus
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 2 months
measure: Incidence rate of progression from stage 1 ROP to zone II stage 3 ROP with plus
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 measured by dried blood spots
timeFrame: 10th day of treatment
Secondary outcomes:
measure: Number of newborns who progress to Stage 2 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 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 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 progress to Stage 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 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: Brescia
country: Italy
facility: Neonatal Intensive Care Unit, Azienda Ospedaliera Spedali Civili di Brescia
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
city: Monza
country: Italy
facility: Neonatal Intensive Care Unit, Azienda Ospedaliera San Gerardo
city: Padova
country: Italy
facility: Piermarocchi Stefano
city: Siena
country: Italy
facility: Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese
city: Varese
country: Italy
facility: Neonatal Intensive Care Unit, Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi
Study officials:
affiliation: A. Meyer University Childrens' Hospital
name: Luca Filippi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Padrini L, Isacchi B, Bilia AR, Pini A, Lanzi C, Masini E, Della Bona ML, Calvani AM, Ceccantini R, la Marca G, Filippi L. Pharmacokinetics and local safety profile of propranolol eye drops in rabbits. Pediatr Res. 2014 Oct;76(4):378-85. doi: 10.1038/pr.2014.108. Epub 2014 Jul 16.
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, Berti E, Padrini L, Araimo G, Regiroli G, Raffaeli G, Bozzetti V, Tagliabue P, Tomasini B, Mori A, Buonocore G, Agosti M, Bossi A, Chirico G, Aversa S, Fortunato P, Osnaghi S, Cavallotti B, Suzani M, Vanni M, Borsari G, Donati S, Nascimbeni G, Nardo D, Piermarocchi S, la Marca G, Forni G, Milani S, Cortinovis I, Calvani M, Bagnoli P, Dal Monte M, Calvani AM, Pugi A, Villamor E, Donzelli G, Mosca F. Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study. Front Pediatr. 2019 May 7;7:180. doi: 10.3389/fped.2019.00180. eCollection 2019.
citation: Filippi L, Cavallaro G, Berti E, Padrini L, Araimo G, Regiroli G, Bozzetti V, De Angelis C, Tagliabue P, Tomasini B, Buonocore G, Agosti M, Bossi A, Chirico G, Aversa S, Pasqualetti R, Fortunato P, Osnaghi S, Cavallotti B, Vanni M, Borsari G, Donati S, Nascimbeni G, la Marca G, Forni G, Milani S, Cortinovis I, Bagnoli P, Dal Monte M, Calvani AM, Pugi A, Villamor E, Donzelli G, Mosca F. Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial. BMC Pediatr. 2017 Jul 14;17(1):165. doi: 10.1186/s12887-017-0923-8.