Oral Propranolol for Prevention of Threshold Retinopathy of Prematurity

Inclusion criteria:

• Preterm infant born before 28 week's gestation

• Birth weight below 1250 g

• At least 5 weeks of age (at randomisation)

• PMA 310/7 - 36 6/7 weeks

• Ophthalmoscopic evidence of incipient ROP (stage 1 or 2, with or without plusdisease in any zone)

• Written informed consent by parents or legal guardian, according to nationalrequirements

Exclusion Criteria:

• ROP stage ≥ 3, AP-ROP or suspected AP-ROP, or any other ROP requiring anintervention (study endpoint already reached).

• Conditions that indicate open label propranolol such as: thyrotoxicosis, arterialhypertension or certain heart diseases (such as tetralogy of Fallot, paroxysmalsupraventricular tachycardia, or long QT syndrome) etc.

• Major congenital malformations or known chromosomal anomalies

• Colobomas and other eye malformations

• PHACE syndrome (posterior fossa anomalies, large infantile hemangiomas of the face,neck, and/or scalp, arterial lesions, cardiac abnormalities/coarctation of theaorta, eye anomalies) (risk of cerebrovascular complications)

• Very large hemangioma (risk of hyperkalemia), as judged by the attending physician

• Medication of the infant with rifampicin or phenobarbitone (enhanced metabolicclearance)

• Chronic kidney impairment (serum creatinine > 1.3 mg/dl [115 μmol/L])

• Severe liver dysfunction (ALT (GPT) > 900 U/L)

• Known hypersensitivity to propranolol or any of the excipients (see 6.3.1.)

• Prinzmetal's angina, Raynaud's phenomenon (severe peripheral arterial circulatorydisturbance), or pheochromocytoma (contraindications for propranolol in adults, notoccurring in newborn infants)

• Any circumstances that make the investigator believe that participation in the studyleads to exceptional medical or organizational problems for the patient

• Conditions that prohibit propranolol therapy such as: Atrio-ventricular block grade 2 or 3 hypertrophic cardiomyopathy, sinoatrial block, uncontrolled heart failure orcardiogenic shock, bronchial asthma

• Medication of the infant or the mother if breastfeeding with clonidine, reserpine,angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists (contraindicated in preterm infants) or antiarrhythmic drugs including amiodarone,propafenone, lidocaine, digoxin/digitoxin, quinidine, verapamil, diltiazem, bepridil (pharmacodynamic interaction)