TY - JOUR
T1 - Study protocol
T2 - 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
AU - Filippi, Luca
AU - Cavallaro, Giacomo
AU - Berti, Elettra
AU - Padrini, Letizia
AU - Araimo, Gabriella
AU - Regiroli, Giulia
AU - Bozzetti, Valentina
AU - De Angelis, Chiara
AU - Tagliabue, Paolo
AU - Tomasini, Barbara
AU - Buonocore, Giuseppe
AU - Agosti, Massimo
AU - Bossi, Angela
AU - Chirico, Gaetano
AU - Aversa, Salvatore
AU - Pasqualetti, Roberta
AU - Fortunato, Pina
AU - Osnaghi, Silvia
AU - Cavallotti, Barbara
AU - Vanni, Maurizio
AU - Borsari, Giulia
AU - Donati, Simone
AU - Nascimbeni, Giuseppe
AU - la Marca, Giancarlo
AU - Forni, Giulia
AU - Milani, Silvano
AU - Cortinovis, Ivan
AU - Bagnoli, Paola
AU - Dal Monte, Massimo
AU - Calvani, Anna Maria
AU - Pugi, Alessandra
AU - Villamor, Eduardo
AU - Donzelli, Gianpaolo
AU - Mosca, Fabio
PY - 2017/7/14
Y1 - 2017/7/14
N2 - Background: Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1).Methods: A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations.Discussion: Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue.
AB - Background: Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1).Methods: A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations.Discussion: Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue.
KW - Propranolol
KW - Beta blocker
KW - Proliferative retinopathy
KW - Angiogenesis
KW - OXYGEN-INDUCED RETINOPATHY
KW - ENDOTHELIAL GROWTH-FACTOR
KW - BETA-ADRENERGIC-RECEPTOR
KW - ORAL PROPRANOLOL
KW - RETINAL NEOVASCULARIZATION
KW - BETA-2-ADRENERGIC RECEPTOR
KW - INFANTILE HEMANGIOMAS
KW - BETA-3-ADRENERGIC RECEPTORS
KW - FUNCTIONAL INVOLVEMENT
KW - VISUAL IMPAIRMENT
U2 - 10.1186/s12887-017-0923-8
DO - 10.1186/s12887-017-0923-8
M3 - Article
C2 - 28709412
SN - 1471-2431
VL - 17
JO - Bmc Pediatrics
JF - Bmc Pediatrics
IS - 1
M1 - 165
ER -