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

NCT02014454 | Completed Phase 2

• 1 other identifier: DROP-PROP
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Retinopathy of Prematurity

Keywords

Retinopathy of prematurity; Propranolol; Eye drops; Newborns; Retinal angiogenesis; Retinal neovascularization

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (6)

• 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

  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

Study Arms (1)

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.

Drug: Propranolol eye drops

Interventions

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.

Propranolol eye drops

Eligibility Criteria

• Age: 1 Month - 4 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (2)

Neonatal Intensive Care Unit, A. Meyer University Childrens' Hospital

Florence, 50139, Italy

Location

Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan

Milan, 20122, Italy

Location

Related Publications (5)

• 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.

  PMID: 24054431 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.

  PMID: 23528535 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.

  PMID: 23205867 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.

  PMID: 23434527 BACKGROUND

• 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.

  PMID: 27814346 DERIVED

MeSH Terms

Conditions

Retinopathy of Prematurity; Retinal Neovascularization

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Luca Filippi, MD

  Meyer Children's Hospital IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 10, 2013
• First Posted: December 18, 2013
• Study Start: November 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: July 7, 2015

Record last verified: 2015-07

Locations

IT (2)