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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propranolol eye drops | Experimental | All the enrolled preterm newborns will receive propranolol as ophthalmic solution (0,1%): 3 microdrops of 6 microliters (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 Early Treatment for Retinopathy of Prematurity Study (ETROP Cooperative Group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol eye drops | Drug | All the enrolled preterm newborns will receive propranolol as ophthalmic solution (0,1%): 3 microdrops of 6 microliters (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 vascularisation, but no more than 60 days. The propranolol treatment will be always associated to the conventional approach adopted by the ETROP Cooperative Group. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence rate of progression from stage 2 ROP to more severe stage ROP (stage 2 or 3 with plus, stage 4 and stage 5) | Eye drop propranolol is considered to be effective in counteracting the progression of ROP if the treatment decreases the incidence 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. | participants will be followed for the duration of hospital stay, an expected average of 2 months |
| Plasma concentrations of propranolol at the steady state | To evaluate the safety of eye drop propranolol we consider the plasma propranolol concentrations at the steady state. In particular it should be always less than 20 ng/ml, which is the plasma concentration, at the steady state, reported after oral administration of propranolol in the PROP-ROP study | 10th day of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Number of newborns who progress to Stage 3 without plus ROP | participants will be followed for the duration of hospital stay, an expected average of 2 months | |
| Number of newborns who progress to Stage 4 or 5 ROP with total or partial retinal detachment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Luca Filippi, MD | Meyer Children's Hospital IRCCS | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Neonatal Intensive Care Unit, A. Meyer University Childrens' Hospital | Florence | 50139 | Italy | |||
| Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24054431 | Background | 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. | |
| 23528535 |
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| ID | Term |
|---|---|
| D012178 | Retinopathy of Prematurity |
| D015861 | Retinal Neovascularization |
| ID | Term |
|---|---|
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
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| participants will be followed for the duration of hospital stay, an expected average of 2 months |
| Number of newborns who need laser treatment | participants will be followed for the duration of hospital stay, an expected average of 2 months |
| Number of newborns who need rescue treatment with bevacizumab | participants will be followed for the duration of hospital stay, an expected average of 2 months |
| Number of newborns who need vitrectomy | participants will be followed for the duration of hospital stay, an expected average of 2 months |
| Collection of adverse events due to eye drop propranolol treatment | participants will be followed for the duration of hospital stay, an expected average of 2 months |
| Milan |
| 20122 |
| Italy |
| Background |
| 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. |
| 23205867 | Background | 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. |
| 23434527 | Background | 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. |
| 27814346 | Derived | 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. |
| D009358 |
| Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009389 | Neovascularization, Pathologic |
| D008679 | Metaplasia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |