Oral Propranolol Versus Placebo for Early Stages of Retinopathy of Prematurity: A Randomized and Prospective Study

NCT01238471 | Completed Phase 1 Results DMC

• 2 other identifiers: 0479-09CTILIsraeli Health Ministry
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

In premature infants, propranolol (Prop) treatment might suppress continuing neo-vascularization (NV) and decelerate the progression of retinopathy of prematurity (ROP) towards its severe stages (III-V), thus avoiding the need of interventions (CRYO and/or LASER photo-coagulation of the ischemic retina and preventing severe ocular sequelae. We therefore plan to prospectively investigate the influence of prop versus placebo in VLBW infants with ROP stage 1 (zone I), with stage 2 or higher (any zone) or with Plus disease, along with close follow up regarding safety of prop administration and its effect on ROP.

Conditions

Retinopathy of Prematurity

Keywords

retinopathy of prematurity; Propranolol; Vascular endothelial growth factor; premature infant

Outcome Measures

Primary Outcomes (1)

• Regression of Retinopathy of Prematurity (ROP) in Premature Infants by Propranolol Therapy

  If ROP regresses without the need for treatment (laser and/or CRYO), this will be considered a favorable outcome. On the other hand, if ROP progresses to require treatment, it will be regarded as an unfavorable outcome. Evidence for regression of ROP was observed by serial retinal examinations performed by ophthalmologists as well as by reduction for the need of invasive interventions such as laser photocoagulation of disease areas in the retina.

  propranolol therapy for up 4 weeks

Secondary Outcomes (1)

• Safety of Propranolol Therapy in Premature Infants

  4 weeks of propranolol therapy in premature infants

Study Arms (2)

Propranolol

EXPERIMENTAL

Oral propranolol for premature infants allocated to this arm by randomization

Drug: propranolol

Oral sucrose 5%

PLACEBO COMPARATOR

Placebo: Oral sucrose 5% for premature infants allocated to control arm by randomization

Drug: sucrose 5%

Interventions

propranolol DRUG

2 mg per kg per day divided in 3 doses for 2-4 weeks

Also known as: beta blocker, deralin

Propranolol

sucrose 5% DRUG

2 ml per Kg per day divided in 3 doses for 2-4 weeks

Also known as: sucrose sugar

Oral sucrose 5%

Eligibility Criteria

• Age: 4 Weeks - 14 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Evidence for ROP that might progress and that includes any one of the following:
• Stage 1 (zone I)
• Stage 2 or higher (zones I, II or III), or Plus disease. The classification of ROP is according to International Classification of Retinopathy of Prematurity (ICROP) 2005 (40) (Appendix I, with scheme of retina showing zones and clock hours).Zone III ROP is not included since it will always regress spontaneously.

You may not qualify if:

• The presence of one or more of the following conditions at enrollment in the study:
• More than 10 episodes of bradycardia of prematurity/day (HR\< 90 bpm) \[
• Atrio-ventricular (A-V) block \[2nd or 3rd degree\]
• Significant congenital heart anomaly \[not including patent ductus arteriosus, patent foramen ovale or small ventricular septal defect\]
• Heart failure
• Hypotension (mean blood pressure \<45 mmHg)
• Hypoglycemia (\<50mg/dL)
• Platelet count \<100000/mm3

Sponsors & Collaborators

• Rambam Health Care Campus: lead
• Hadassah Medical Organization: collaborator
• Laniado Hospital: collaborator
• Nazareth Hospital: collaborator

Study Sites (4)

Rambam Health Care Campus

Haifa, 31096, Israel

Location

Hadassah Medical Organization

Jerusalem, Israel

Location

Nazareth Hospital

Nazareth, Israel

Location

Laniado Hospital

Netanya, Israel

Location

MeSH Terms

Conditions

Retinopathy of Prematurity; Premature Birth

Interventions

Propranolol; Adrenergic beta-Antagonists

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Results Point of Contact

• Title: Professor Imad Makhoul
• Organization: Rambam Medical Center

makhoul@rambam.health.gov.il

972-4-8542219

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2010
• First Posted: November 10, 2010
• Study Start: May 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: July 1, 2012
• Last Updated: June 26, 2014
• Results First Posted: June 10, 2014

Record last verified: 2014-06

Locations

IL (4)