Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02014454
Other study ID # DROP-PROP
Secondary ID
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


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
See also
  Status Clinical Trial Phase
Completed NCT05043077 - Efficacy and Safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening Phase 4
Completed NCT04838665 - Changes in Vital Signs and Pupil Diameter Related to Pharmacologic Mydriasis in Premature Infants: A Randomized Double Blind Clinical Study Phase 4
Completed NCT04408807 - Stress Induced by Screening for Retinopathy of Prematurity - Should Speculum and Indentation Rather be Avoided N/A
Recruiting NCT03083431 - Oral Propranolol for Prevention of Threshold Retinopathy of Prematurity Phase 2
Enrolling by invitation NCT04985448 - Real World Study of the Effectiveness and Safety of Conbercept Ophthalmic Injection in the Treatment of Retinopathy of Prematurity - Multicenter, Retrospective and Observational Study Based on Real World Data
Recruiting NCT02090322 - Bevacizumab 0.500MG Intravitreal There Isn't Lower Than 0.625MG in the Treatment of ROP Type 1 N/A
Completed NCT00872664 - Skin and Serum Carotenoids in Preterm Infants Fed on a Formula Supplemented With Carotenoids N/A
Unknown status NCT00254176 - Cysteine Supplementation in Critically Ill Neonates Phase 2/Phase 3
Completed NCT06452524 - Prematurity and Ophthalmological Changes
Completed NCT04101721 - Study to Assess the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Compared to Laser Photocoagulation in Patients With Retinopathy of Prematurity Phase 3
Enrolling by invitation NCT02050971 - Autologous Cord Blood Infusion for the Prevention and Treatment of Prematurity Complications In Preterm Neonates Phase 1
Terminated NCT01335113 - A Scan Ultrasonography in the Evaluation of Retinopathy of Prematurity
Active, not recruiting NCT00027222 - The Early Treatment for Retinopathy of Prematurity Study (ETROP) Phase 2/Phase 3
Recruiting NCT06109285 - Validation of i-ROP DL to Detect More Than Mild ROP N/A
Completed NCT01861470 - REDEXAM - Reducing Painful Eye Examinations in Preterm Infants N/A
Terminated NCT00634972 - Efficient Study of ACULAR in Inhibiting Proliferative Retinopathy in Prematurity Phase 4
Completed NCT05701124 - Intravitreal Ranibizumab Injection for Aggressive Versus Type 1 Prethreshold Retinopathy of Prematurity Phase 3
Completed NCT04092127 - Pain of Premature Babies and RetCam (DOLICAM)
Completed NCT04621136 - PhaseI/II Investigator-Initiated Trial to Investigate Safety and Efficacy of Ripasudil in Patients With Retinopathy of Prematurity Phase 1/Phase 2
Completed NCT04883931 - Mother Milk as a Eye Drop & Premature Retinopathy N/A