Oral Propranolol for prevention of threshold retinopathy of prematurity

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 276

Inclusion Criteria

• Preterm infant born before 28 weeks gestation
• Birth weight below 1250 g
• Alive at 5 weeks of age
• Postmenstrual age 31 0/7 – 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 276
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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, or 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 µM])
• 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/µL 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
• Lack of willingness to storage and disclosure of pseudonymous disease data in the context of the clinical trial

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and efficacy of orally administered propranolol to reduce the risk of threshold retinopathy of prematurity in extremely preterm infants<br>;Secondary Objective: To assess the safety and efficacy of orally administered propranolol to reduce the rate of extremely preterm infants requiring local interventions for severe retinopathy of prematurity<br>;Primary end point(s): Primary endpoint: <br>Survival without threshold ROP (stage 3 or more severe ROP(including aggressive posterior ROP)) ;Timepoint(s) of evaluation of this end point: time frame: 48 weeks postmenstrual age<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary endpoints: <br>Survival without ROP treated with ablative laser surgery or intravitreal VEGF antagonists<br><br>;Timepoint(s) of evaluation of this end point: time frame: 48 weeks postmenstrual age

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