search
Back to results

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

Primary Purpose

Retinopathy of Prematurity

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Propranolol 0.2% eye drops
Sponsored by
Azienda Ospedaliero, Universitaria Meyer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Retinopathy of Prematurity focused on measuring Retinopathy of prematurity, Propranolol, Newborn, Eye Drops, Retinal angiogenesis, Retinal neovascularization

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Neonatal Intensive Care Unit, Azienda Ospedaliera Spedali Civili di Brescia
  • Neonatal Intensive Care Unit, A. Meyer University Childrens' Hospital
  • Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan
  • Neonatal Intensive Care Unit, Azienda Ospedaliera San Gerardo
  • Piermarocchi Stefano
  • Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese
  • Neonatal Intensive Care Unit, Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Propranolol 0.2% eye drops

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence rate of progression from stage 1 ROP to zone II stage 2 ROP with plus
Incidence rate of progression from stage 1 ROP to zone II stage 3 ROP with plus
Plasma concentrations of propranolol at the steady state measured by dried blood spots

Secondary Outcome Measures

Number of newborns who progress to Stage 2 without plus ROP
Number of newborns who progress to Stage 3 without plus ROP
Number of newborns who progress to Stage 4 with total or partial retinal detachment
Number of newborns who progress to Stage 5 ROP with total or partial retinal detachment
Number of newborns who need vitrectomy
Collection of adverse events due to eye drop propranolol treatment

Full Information

First Posted
July 19, 2015
Last Updated
August 29, 2018
Sponsor
Azienda Ospedaliero, Universitaria Meyer
search

1. Study Identification

Unique Protocol Identification Number
NCT02504944
Brief Title
Safety and Efficacy of Propranolol 0.2% Eye Drops in Treating Retinopathy of Premature: A Pilot Study (DROP-ROP-0.2%)
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%)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
August 2018 (Actual)
Study Completion Date
August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliero, Universitaria Meyer

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinopathy of Prematurity
Keywords
Retinopathy of prematurity, Propranolol, Newborn, Eye Drops, Retinal angiogenesis, Retinal neovascularization

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
98 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Propranolol 0.2% eye drops
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Propranolol 0.2% eye drops
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence rate of progression from stage 1 ROP to zone II stage 2 ROP with plus
Time Frame
participants will be followed for the duration of hospital stay, an expected average of 2 months
Title
Incidence rate of progression from stage 1 ROP to zone II stage 3 ROP with plus
Time Frame
participants will be followed for the duration of hospital stay, an expected average of 2 months
Title
Plasma concentrations of propranolol at the steady state measured by dried blood spots
Time Frame
10th day of treatment
Secondary Outcome Measure Information:
Title
Number of newborns who progress to Stage 2 without plus ROP
Time Frame
participants will be followed for the duration of hospital stay, an expected average of 2 months
Title
Number of newborns who progress to Stage 3 without plus ROP
Time Frame
participants will be followed for the duration of hospital stay, an expected average of 2 months
Title
Number of newborns who progress to Stage 4 with total or partial retinal detachment
Time Frame
participants will be followed for the duration of hospital stay, an expected average of 2 months
Title
Number of newborns who progress to Stage 5 ROP with total or partial retinal detachment
Time Frame
participants will be followed for the duration of hospital stay, an expected average of 2 months
Title
Number of newborns who need vitrectomy
Time Frame
participants will be followed for the duration of hospital stay, an expected average of 2 months
Title
Collection of adverse events due to eye drop propranolol treatment
Time Frame
participants will be followed for the duration of hospital stay, an expected average of 2 months

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luca Filippi, MD
Organizational Affiliation
A. Meyer University Childrens' Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Neonatal Intensive Care Unit, Azienda Ospedaliera Spedali Civili di Brescia
City
Brescia
Country
Italy
Facility Name
Neonatal Intensive Care Unit, A. Meyer University Childrens' Hospital
City
Florence
ZIP/Postal Code
50139
Country
Italy
Facility Name
Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan
City
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
Neonatal Intensive Care Unit, Azienda Ospedaliera San Gerardo
City
Monza
Country
Italy
Facility Name
Piermarocchi Stefano
City
Padova
ZIP/Postal Code
35100
Country
Italy
Facility Name
Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese
City
Siena
Country
Italy
Facility Name
Neonatal Intensive Care Unit, Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi
City
Varese
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
25029260
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.
Results Reference
background
PubMed Identifier
24054431
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.
Results Reference
background
PubMed Identifier
23528535
Citation
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.
Results Reference
background
PubMed Identifier
23205867
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.
Results Reference
background
PubMed Identifier
23434527
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.
Results Reference
background
PubMed Identifier
31134171
Citation
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.
Results Reference
derived
PubMed Identifier
28709412
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs