Propranolol 0.1% eye micro-drops in newborns with retinopathy of prematurity: a pilot clinical trial.
Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. This study evaluated safety and efficacy of propranolol eye micro-drops in preterm newborns with ROP.



A multicenter open-label trial, planned according to the Simon optimal two-stage design, was performed to analyze safety and efficacy of propranolol micro-drops in newborns with stage 2 ROP. To this end, hemodynamic and respiratory parameters were monitored, and blood samples were collected weekly, for 3 wk. Propranolol plasma levels were also monitored. The progression of the disease was evaluated with serial ophthalmologic examinations.



Twenty-three newborns were enrolled. Since the fourth of the first 19 newborns enrolled in the first stage of the study showed a progression to stage 2 or 3 with plus, the second stage was prematurely discontinued. Even though the objective to complete the second stage was not achieved, the percentage of ROP progression (26%) was similar to that obtained previously with oral propranolol administration. However, no adverse effects were observed and propranolol plasma levels were significantly lower than those measured after oral administration.



Propranolol 0.1% eye micro-drops are well tolerated, but not sufficiently effective. Further studies are required to identify the optimal dose and administration schedule.
Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy.
Luca
L
Filippi
Neonatal Intensive Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Giacomo
G
Cavallaro
Department of Biology, Unit of General Physiology, University of Pisa, Pisa, Italy.
Paola
P
Bagnoli
Department of Biology, Unit of General Physiology, University of Pisa, Pisa, Italy.
Massimo
M
Dal Monte
Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy.
Patrizio
P
Fiorini
Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy.
Elettra
E
Berti
Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy.
Letizia
L
Padrini
Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy.
Gianpaolo
G
Donzelli
Neonatal Intensive Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Gabriella
G
Araimo
Neonatal Intensive Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Gloria
G
Cristofori
Neonatal Intensive Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Monica
M
Fumagalli
Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Newborn Screening, Biochemistry and Pharmacology Laboratory, Meyer Children's University Hospital, Florence, Italy.
Giancarlo
G
la Marca
Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Newborn Screening, Biochemistry and Pharmacology Laboratory, Meyer Children's University Hospital, Florence, Italy.
Maria Luisa
ML
Della Bona
Pediatric Ophthalmology, A. Meyer" University Children's Hospital, Florence, Italy.
Roberta
R
Pasqualetti
Pediatric Ophthalmology, A. Meyer" University Children's Hospital, Florence, Italy.
Pina
P
Fortunato
Department of Ophthalmology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Polclinico, Milan, Italy.
Silvia
S
Osnaghi
Department of Pediatrics, Obstetrics and Reproductive Medicine, Neonatal Intensive Care Unit, University Hospital of Siena, Policlinico Santa Maria alle Scotte, Siena, Italy.
Barbara
B
Tomasini
Department of Pediatrics, Obstetrics and Reproductive Medicine, Neonatal Intensive Care Unit, University Hospital of Siena, Policlinico Santa Maria alle Scotte, Siena, Italy.
Maurizio
M
Vanni
Department of Pharmacy, "A. Meyer" University Children's Hospital, Florence, Italy.
Anna Maria
AM
Calvani
Laboratory "G.A. Maccacro", Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Silvano
S
Milani
Laboratory "G.A. Maccacro", Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Ivan
I
Cortinovis
Clinical Trial Office, "A. Meyer" University Children's Hospital, Florence, Italy.
Alessandra
A
Pugi
Neonatal Intensive Care Unit, Del Ponte Hospital, Varese, Italy.
Massimo
M
Agosti
Neonatal Intensive Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Fabio
F
Mosca
D060433:Administration, Ophthalmic; D000284:Administration, Oral; D000287:Administration, Topical; D018450:Disease Progression; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D061214:Patient Safety; D010865:Pilot Projects; D011433:Propranolol / Q000008:administration & dosage* / Q000097:blood; D012119:Respiration; D012178:Retinopathy of Prematurity / Q000188:drug therapy*
D011433:Propranolol