propranolol hydrochloride for Retinopathy of prematurity

Inclusion criteria

• {"criterion_text":"- Preterm infant born before 28 weeks gestation\n- Birth weight below 1250 g\n- Alive at 5 weeks of age\n- Postmenstrual age 31 0/7 – 36 6/7 weeks\n- Ophthalmoscopic evidence of incipient ROP (stage 1 or 2, with or without plus disease)\n- 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

• {"criterion_text":"- ROP stage ≥ 3, AP-ROP or suspected AP-ROP, or any other ROP requiring an intervention (study endpoint already reached)\n- Chronic kidney impairment (creatinine > 1.3 mg/dl [100 μM])\n- Persistent hypoglycemia (blood glucose < 36 mg/dl [2.0 mM] in 3 consecutive samples immediately preceding enrollment)\n- Thyrotoxicosis, arterial hypertension or congenital heart diseases requiring open-label propranolol treatment (such as tetralogy of Fallot, paroxysmal supraventricular tachycardia, or long QT syndrome)\n- Persistent hyperkalemia (venous serum potassium > 5.9 mM in 3 consecutive samples immediately preceding enrollment)\n- Persistent neutropenia (absolute neutrophil counts <1,000/μL in 3 consecutive samples immediately preceding enrollment)\n- Known hypersensitivity to propranolol or any of the excipients\n- Prinzmetal's angina, Raynaud's phenomenon (severe peripheral arterial circulatory disturbance), or pheochromocytoma (contraindications for propranolol in adults, not occurring in newborn infants)\n- Participation in another pharmacological interventional clinical trial\n- Any circumstances that make the investigator believe that in the infant’s own interest, he/she should no longer receive the study medication\n- Lack of willingness to storage and disclosure of pseudonymous disease data in the context of the clinical trial\n- 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)\n- Atrio-ventricular block grade 2 or 3 (contraindication for propranolol)\n- Sinuatrial block (contraindication for propranolol)\n- Uncontrolled heart failure or cardiogenic shock (contraindication for propranolol)\n- Acute severe infection (inclusion may be postponed until infection has resolved)\n- Bronchial asthma\n- Major congenital malformations or known chromosomal anomalies\n- Colobomas and other eye malformations\n- > 7 days after first ROP diagnosis (day 1 = first ROP diagnosis)\n- Previous or current conditions that indicated/indicate beta-blocker therapy, open label propranolol such as: thyrotoxicosis, arterial hypertension or certain heart diseases (such as tetralogy of Fallot, paroxysmal supraventricular tachycardia long QT syndrome, or hypertrophic cardiomyopathy)\n- Very large hemangioma (risk of hyperkalemia), as judged by the attending physician\n- Heart rate consistently (>1 h) < 100/min\n- Noninvasive mean arterial pressure consistently (>1 h) <40 mmHg\n- Medication of the infant or the mother if breastfeeding with clonidine, reserpine, angiotensin-converting enzyme inhibitors, angiotensinreceptor antagonists, or antiarrhythmic drugs including amiodarone, propafenone, lidocaine, digoxin/digitoxin, quinidine, verapamil, diltiazem, or bepridil (pharmacodynamic interaction)\n- Medication of the infant with rifampicin or phenobarbitone (enhanced metabolic clearance), clonidine, antiarrhythmic drugs (amiodarone, propafenone, lidocaine, digoxin/digitoxin, quinidine), verapamil, diltiazem, bepridil), antihypertensive agents (reserpine, angiotensinconverting enzyme inhibitors, angiotensin-receptor antagonists, (pharmacodynamic drug interaction)\n- Concurrent treatment with insulin (risk of hypoglycemia)\n- Severe liver dysfunction (GPT > 900 U/l)"}

Primary endpoints

• {"endpoint_text":"- Survival without threshold ROP (stage 3 or more severe ROP(including aggressive posterior ROP))","definition_or_measurement_approach":"Defined as survival without development of threshold retinopathy of prematurity, i.e., absence of stage 3 or more severe ROP including aggressive posterior ROP (assessed by ophthalmologic examination)."}

Secondary endpoints

• {"endpoint_text":"- Time to adverse ophthalmological outcome in days\n- Ophthalmological outcome categorized as survival without adverse ophthalmological outcome, or death\n- Survival until 48 weeks PMA without ROP, treated with ablative laser surgery or intravitreal VEGF antagonists\n- Death until discharge\n- Death until 48 weeks PMA\n- ROP retreatment: Need for repeated ROP therapy in infants treated with anti-VEGF-antagonists until 70 ( 2 weeks) PMA","definition_or_measurement_approach":"Time to adverse ophthalmological outcome: measured in days from baseline to event. Outcomes assessed by ophthalmologic examination and categorized as specified. Survival until specified postmenstrual ages (PMA) measured as alive without ROP or without requiring specified treatments at 48 weeks PMA. Death endpoints measured up to discharge or up to 48 weeks PMA. ROP retreatment measured as need for repeated ROP therapy until ~70 PMA."}

Germany

Earliest CTIS Part Ii Submission Date

09-10-2024

Latest Decision Or Authorization Date

09-04-2025

Processing Time Days

182

Number Of Sites

8

Number Of Participants

100

Primary sponsor

Full Name

Universitaetsklinikum Tuebingen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Co-sponsors

• Universität Zürich - Klinik für Neonatologie