Safety and Efficacy of Propranolol in Newborns With Retinopathy of Prematurity

NCT ID: NCT01079715

Last Updated: 2012-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2012-10-31

Brief Summary

The purpose of this study is to determine whether the administration of propranolol is effective in the treatment of the retinopathy of the prematurity.

Detailed Description

Retinopathy of Prematurity (ROP) is still a major cause of blindness in children in developed countries around the world, and an increasing cause of blindness in developing countries. The ablation of the retina with photocoagulation by laser or cryotherapy reduces the incidence of blindness by suppressing the neovascular phase of ROP. However, the visual outcomes after treatment are often poor. The development of ROP depends largely from vascular endothelial growth factor (VEGF). The reduction of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP.

The purpose of this study is to evaluate whether the administration of propranolol is safe and is able to reduce the incidence of blindness by suppressing the neovascular phase of ROP compared to a control group receiving conventional laser therapy.

Conditions

Retinopathy of Prematurity

Keywords

Newborn; Retinal Diseases; Angiogenesis Modulating Agents; Adrenergic beta-Antagonists

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Propranolol

Oral Propranolol administration is the experimental arm of this study

Group Type: EXPERIMENTAL

Propranolol

Intervention Type: DRUG

Dosage of 0.5mg/Kg oral, every 6 hours. The study will be discontinued immediately in the presence of serious adverse effects attributable to the pharmacological actions of propranolol (severe hypotension, bradycardia or bronchospasm).

In case such events occur in any of the 3 groups of gestational age, the study could start again with half dose (0.25mg/Kg oral, every 6 hours) after notification to the Ethics Committee.

In case of surgery or induction of anesthesia during the administration of propranolol, the drug should be discontinued at least 24 hours before surgery.

In cases of severe hypotension or bradycardia may be administered one or more of the following drugs:

• Atropine.
• Isoproterenol hydrochloride (isoprenaline.
• Terlipressin.
• Glucagon In case of severe bronchospasm may be used salbutamol aerosol or salbutamol + ipratropium bromide. Betamethasone could be used for aerosol or systemic (intravenous or intramuscular).

Control

Control arm is treated following the standard treatment schedule of Early Treatment For Retinopathy Of Prematurity Cooperative Group

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Propranolol

Dosage of 0.5mg/Kg oral, every 6 hours. The study will be discontinued immediately in the presence of serious adverse effects attributable to the pharmacological actions of propranolol (severe hypotension, bradycardia or bronchospasm).

In case such events occur in any of the 3 groups of gestational age, the study could start again with half dose (0.25mg/Kg oral, every 6 hours) after notification to the Ethics Committee.

In case of surgery or induction of anesthesia during the administration of propranolol, the drug should be discontinued at least 24 hours before surgery.

In cases of severe hypotension or bradycardia may be administered one or more of the following drugs:

• Atropine.
• Isoproterenol hydrochloride (isoprenaline.
• Terlipressin.
• Glucagon In case of severe bronchospasm may be used salbutamol aerosol or salbutamol + ipratropium bromide. Betamethasone could be used for aerosol or systemic (intravenous or intramuscular).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Infants who have been screened for ROP (≤ 32 weeks gestation) who develop Stage 2 ROP in zone II without plus.

2. Informed Consent from a parent

Exclusion Criteria

1. Newborns with one or more of the following conditions at the enrollment in the study:

• Heart failure.
• Recurrent episodes of bradycardia (Heart rate less than 90 bpm).
• Atrio-ventricular block (second or third degree).
• Significant congenital heart anomaly, not including patent ductus arteriosus, patent foramen ovale or small ventricular septal defect.
• Hypotension.
• Renal failure.
• Cerebral hemorrhage.
• Other diseases which contraindicate the use of beta-blockers

2. Newborns with ROP stages more advances than Stage 2 in zone II without plus.

3. Informed Consent from a parent refused. This will mean that an infant automatically will receive standard laser therapy. No data will be used from an infant without Informed Consent.

• Minimum Eligible Age: 22 Weeks
• Maximum Eligible Age: 32 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ospedale Maggiore Policlinico Mangiagalli e Regina Elena

OTHER

Sponsor Role: collaborator

Meyer Children's Hospital IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Luca Filippi

Dr. Luca Filippi

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luca Filippi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliero-Universitaria A. Meyer, Firenze, Italy

Locations

Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Meyer

Florence, , Italy

Neonatal Intensive Care Unit - Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico

Milan, , Italy

Countries

Italy

References

Filippi L, Cavallaro G, Fiorini P, Daniotti M, Benedetti V, Cristofori G, Araimo G, Ramenghi L, La Torre A, Fortunato P, Pollazzi L, la Marca G, Malvagia S, Bagnoli P, Ristori C, Dal Monte M, Bilia AR, Isacchi B, Furlanetto S, Tinelli F, Cioni G, Donzelli G, Osnaghi S, Mosca F. Study protocol: safety and efficacy of propranolol in newborns with Retinopathy of Prematurity (PROP-ROP): ISRCTN18523491. BMC Pediatr. 2010 Nov 18;10:83. doi: 10.1186/1471-2431-10-83.

Reference Type: BACKGROUND

PMID: 21087499 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24054431 (View on PubMed)

Related Links

http://druginfo.nlm.nih.gov/

Drug information

Other Identifiers

EudraCT Number 2010-018737-21

Identifier Type: -

Identifier Source: org_study_id