Safety and Efficacy of Propranolol Eye Drops in Treating Retinopathy of Premature

Retinopathy of Prematurity Clinical Trial

— DROP-PROP  

Official title:

Safety and Efficacy of Propranolol Eye Drops in Newborns With Retinopathy of Premature (DROP-PROP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02014454
• Other study ID #: DROP-PROP
• Status: Completed
• Phase: Phase 2
• First received: December 10, 2013
• Last updated: July 6, 2015
• Start date: November 2013
• Est. completion date: August 2014

Study information

• Verified date: July 2015
• Source: Azienda Ospedaliero, Universitaria Meyer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines AgencyEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 4 Months

Eligibility

Inclusion Criteria:

• Preterm newborns (gestational age 23-32 weeks) with stage 2 ROP, zone II without plus.

• A signed parental informed consent.

Exclusion Criteria:

• Newborns with heart failure;

• Newborns with congenital cardiovascular anomalies, except for persistent ductus arteriosus, patent foramen ovale and small ventricular septal defects;

• Newborns with recurrent bradycardia (heart rate < 90 beat per minute);

• Newborns with second or third degree atrioventricular block;

• Newborns with hypotension;

• Newborns with renal failure;

• Newborns with actual cerebral haemorrhage;

• Newborns with other diseases which contraindicate the use of beta-adrenoreceptor blockers.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• Propranolol eye drops
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.

Locations

Country	Name	City	State
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

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero, Universitaria Meyer

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	Yes
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	No
Secondary	Number of newborns who progress to Stage 4 or 5 ROP with total or partial retinal detachment		participants will be followed for the duration of hospital stay, an expected average of 2 months	No
Secondary	Number of newborns who need laser treatment		participants will be followed for the duration of hospital stay, an expected average of 2 months	No
Secondary	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	No
Secondary	Number of newborns who need vitrectomy		participants will be followed for the duration of hospital stay, an expected average of 2 months	No
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	Yes