Gender: All
Maximum age: 104 Days
Minimum age: 35 Days
Inclusion criteria: ? Preterm infant born before 28 weeks gestation
? Birth weight below 1250 g
? Alive at 5 weeks of age
? Postmenstrual age 310/7 ? 36 6/7 weeks
? Ophthalmoscopic evidence of incipient ROP (stage 1 or 2, with or without plus disease)
? Written informed consent by parents or legal guardian, including saving and propagation of pseudonymous medical data for study purposes, according to national requirements
Exclusion criteria: ? ROP stage 3 at time of inclusion (endpoint already reached)
? Thyrotoxicosis, arterial hypertension or congenital heart diseases requiring open-label propranolol treatment (such as tetralogy of Fallot, paroxysmal supraventricular tachycardia,
or long QT syndrome)
? Atrio-ventricular block grade 2 or 3 (contraindication for propranolol)
? Sinuatrial block (contraindication for propranolol)
? Uncontrolled heart failure or cardiogenic shock (contraindication for propranolol)
? Acute severe infection (inclusion may be postponed until infection has resolved)
? Bronchial asthma
? 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 the aorta, eye anomalies) (risk of cerebrovascular complications)
? Very large hemangioma (risk of hyperkalemia), as judged by the attending physician
? Heart rate consistently (>1 h) < 100/min
? Noninvasive mean arterial pressure consistently (>1 h)
<40 mmHg
? Medication of the infant or the mother if breastfeeding with clonidine, reserpine, angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists, antiarrhythmic
drugs including amiodarone, propafenone, lidocaine, digoxin/digitoxin, quinidine, verapamil, diltiazem, or bepridil (pharmacodynamic interaction)
? Medication of the infant with rifampicin or phenobarbitone (enhanced metabolic clearance)
? Concurrent treatment with insulin (risk of hypoglycemia)
? Severe liver dysfunction (GPT > 900 U/L)
? Chronic kidney impairment (creatinine > 1.3 mg/dl [100 ?M])
? Persistent hypoglycemia (blood glucose < 36 mg/dl [2.0 mM] in 3 consecutive samples immediately preceding enrollment)
? Persistent hyperkalemia (venous serum potassium > 5.9 mM in 3 consecutive samples immediately preceding enrollment)
? Persistent neutropenia (absolute neutrophil counts <1,000/?L in 3 consecutive samples immediately preceding enrollment)
? Known hypersensitivity to propranolol or any of the excipients
? Prinzmetal?s angina, Raynaud?s phenomenon (severe peripheral arterial circulatory disturbance), or pheochromocytoma (contraindications for propranolol in adults, not occurring in newborn infants)
? Participation in another pharmacological interventional clinical trial
? Any circumstances that make the investigator believe that participation in the study leads to exceptional medical or organizational problems for the patient.
