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Retinopathy of PrematurityPhase 2DROP-PROPNCT02014454

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

A Phase 2 study testing Propranolol eye drops in people with Retinopathy of Prematurity, run by Meyer Children's Hospital IRCCS at 2 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 1 month to 4 months
Conditions the study is for
Retinopathy of Prematurity
What is being tested?
Propranolol eye drops
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
2 sitesItaly
Study dates
Nov 2013to Aug 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 month to 4 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

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

Who cannot join

  • 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.

Trial locations and contacts

2 sites in 1 country.

Italy2 sites

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

    Florence, 50139

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

    Milan, 20122

Other trials in Italy

About this study

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

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.

Being tested
Propranolol eye drops
Keywords
Retinopathy of prematurity, Propranolol, Eye drops, Newborns, Retinal angiogenesis, Retinal neovascularization
Medical subject headings
Retinopathy of Prematurity, Retinal Neovascularization

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Propranolol eye dropsDrug

    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.

Study groups in NCT02014454
Study groupRoleWhat they receive
Propranolol eye dropsExperimentalAll 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.
Receives: Drug: Propranolol eye drops

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months

  2. 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

    Measured: 10th day of treatment

Secondary outcomes (6)

  1. Number of newborns who progress to Stage 3 without plus ROP

    Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months

  2. Number of newborns who progress to Stage 4 or 5 ROP with total or partial retinal detachment

    Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months

  3. Number of newborns who need laser treatment

    Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months

  4. Number of newborns who need rescue treatment with bevacizumab

    Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months

  5. Number of newborns who need vitrectomy

    Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months

  6. Collection of adverse events due to eye drop propranolol treatment

    Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Dec 2013 (estimated)
  2. Study startNov 2013
  3. Primary completionAug 2014
  4. Study completionAug 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02014454
Sponsor's protocol ID
DROP-PROP
Acronym
DROP-PROP
Status last verified
Jul 2015
First submitted
10 Dec 2013
Last updated
7 Jul 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 24054431

  • 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.

    PubMed 23528535

  • 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.

    PubMed 23205867

  • 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.

    PubMed 23434527

  • 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.

    PubMed 27814346

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Propranolol eye drops in people with Retinopathy of Prematurity, run by Meyer Children's Hospital IRCCS at 2 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence rate of progression from stage 2 ROP to more severe stage ROP (stage 2 or 3 with plus, stage 4 and stage 5) (time frame: participants will be followed for the duration of hospital stay, an expected average of 2 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02014454, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2015.

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