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

NCT02504944 | Completed Phase 2

• 1 other identifier: DROP-ROP-0.2%
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Retinopathy of Prematurity

Keywords

Retinopathy of prematurity; Propranolol; Newborn; Eye Drops; Retinal angiogenesis; Retinal neovascularization

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• Plasma concentrations of propranolol at the steady state measured by dried blood spots

  10th day of treatment

Secondary Outcomes (6)

• 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

• 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 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 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

• 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 0.2% eye drops

EXPERIMENTAL

Enrolled preterm newborns will receive propranolol as ophthalmic solution (0.2%). The treatment will be started as soon as the diagnosis of stage 1 ROP is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days. 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. Propranolol concentrations will be measured on dried blood spots at the steady state (10th day). Serial ophthalmological evaluations will be planned to monitor the efficacy of the treatment, the ROP progression and the possible complications.

Drug: Propranolol 0.2% eye drops

Interventions

Propranolol 0.2% eye drops DRUG

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.

Propranolol 0.2% eye drops

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Preterm newborns (gestational age 23-32 weeks) with stage 1 ROP
• A signed parental informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (7)

Neonatal Intensive Care Unit, Azienda Ospedaliera Spedali Civili di Brescia

Brescia, Italy

Location

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

Neonatal Intensive Care Unit, Azienda Ospedaliera San Gerardo

Monza, Italy

Location

Piermarocchi Stefano

Padua, 35100, Italy

Location

Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese

Siena, Italy

Location

Neonatal Intensive Care Unit, Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi

Varese, Italy

Location

Related Publications (7)

• 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.

  PMID: 25029260 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.

  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, Berti E, Padrini L, Araimo G, Regiroli G, Raffaeli G, Bozzetti V, Tagliabue P, Tomasini B, Mori A, Buonocore G, Agosti M, Bossi A, Chirico G, Aversa S, Fortunato P, Osnaghi S, Cavallotti B, Suzani M, Vanni M, Borsari G, Donati S, Nascimbeni G, Nardo D, Piermarocchi S, la Marca G, Forni G, Milani S, Cortinovis I, Calvani M, Bagnoli P, Dal Monte M, Calvani AM, Pugi A, Villamor E, Donzelli G, Mosca F. Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study. Front Pediatr. 2019 May 7;7:180. doi: 10.3389/fped.2019.00180. eCollection 2019.

  PMID: 31134171 DERIVED

• Filippi L, Cavallaro G, Berti E, Padrini L, Araimo G, Regiroli G, Bozzetti V, De Angelis C, Tagliabue P, Tomasini B, Buonocore G, Agosti M, Bossi A, Chirico G, Aversa S, Pasqualetti R, Fortunato P, Osnaghi S, Cavallotti B, Vanni M, Borsari G, Donati S, Nascimbeni G, la Marca G, Forni G, Milani S, Cortinovis I, Bagnoli P, Dal Monte M, Calvani AM, Pugi A, Villamor E, Donzelli G, Mosca F. Study protocol: 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. BMC Pediatr. 2017 Jul 14;17(1):165. doi: 10.1186/s12887-017-0923-8.

  PMID: 28709412 DERIVED

MeSH Terms

Conditions

Retinopathy of Prematurity; Retinal Neovascularization

Interventions

Propranolol; Ophthalmic Solutions

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

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• Luca Filippi, MD

  A. Meyer University Childrens' Hospital

  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: July 19, 2015
• First Posted: July 22, 2015
• Study Start: July 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: August 31, 2018

Record last verified: 2018-08

Locations

IT (7)