Safety and Efficacy of Propranolol 0.2% Eye Drops in Treating Retinopathy of Premature: A Pilot Study (DROP-ROP-0.2%)

Retinopathy of Prematurity Clinical Trial

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%)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02504944
• Other study ID #: DROP-ROP-0.2%
• Status: Completed
• Phase: Phase 2
• Start date: July 2015
• Est. completion date: August 2018

Study information

• Verified date: August 2018
• Source: Azienda Ospedaliero, Universitaria Meyer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• Propranolol 0.2% eye drops
Enrolled preterm newborns will receive propranolol as ophthalmic solution (0.2%): 3 microdrops of 6 microliters (µL) propranolol solution (= 6 µg propranolol/microdrop) will be topically applied with a calibrated pipette, in each eye, four times daily (every 6 hours). Propranolol treatment will be always associated to the conventional approach adopted by the Early Treatment for Retinopathy of Prematurity Study (ETROP) Cooperative Group.

Locations

Country	Name	City	State
Italy	Neonatal Intensive Care Unit, Azienda Ospedaliera Spedali Civili di Brescia	Brescia
Italy	Neonatal Intensive Care Unit, A. Meyer University Childrens' Hospital	Florence
Italy	Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan	Milan
Italy	Neonatal Intensive Care Unit, Azienda Ospedaliera San Gerardo	Monza
Italy	Piermarocchi Stefano	Padova
Italy	Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese	Siena
Italy	Neonatal Intensive Care Unit, Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi	Varese

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero, Universitaria Meyer

Country where clinical trial is conducted

Italy, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate of progression from stage 1 ROP to zone II stage 2 ROP with plus		participants will be followed for the duration of hospital stay, an expected average of 2 months
Primary	Incidence rate of progression from stage 1 ROP to zone II stage 3 ROP with plus		participants will be followed for the duration of hospital stay, an expected average of 2 months
Primary	Plasma concentrations of propranolol at the steady state measured by dried blood spots		10th day of treatment
Secondary	Number of newborns who progress to Stage 2 without plus ROP		participants will be followed for the duration of hospital stay, an expected average of 2 months
Secondary	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
Secondary	Number of newborns who progress to Stage 4 with total or partial retinal detachment		participants will be followed for the duration of hospital stay, an expected average of 2 months
Secondary	Number of newborns who progress to Stage 5 ROP with total or partial retinal detachment		participants will be followed for the duration of hospital stay, an expected average of 2 months
Secondary	Number of newborns who need vitrectomy		participants will be followed for the duration of hospital stay, an expected average of 2 months
Secondary	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