Retinopathy of Prematurity Clinical Trial
— RoPropOfficial title:
Oral Propranolol for Prevention of Threshold Retinopathy of Prematurity
Extremely premature infants are at risk of developing a potentially blinding eye disease, called retinopathy of prematurity (ROP). Currently available treatment, consisting of laser surgery or injection of drugs into the eye balls, may prevent most but not all cases of permanent ROP-mediated blindness. Both types of treatment are associated with significant costs and side effects. An orally administered drug commonly used to treat hypertension, propranolol, may be effective in halting progression of ROP to severe stages, as suggested by preliminary data from small studies. As severe (threshold) ROP is an overall rare disease, the effectiveness of propranolol in combating ROP can only be assessed in a large, multicenter randomized controlled trial involving hospitals caring for extremely preterm infants of diverse origin.
Status | Recruiting |
Enrollment | 276 |
Est. completion date | July 2026 |
Est. primary completion date | December 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 5 Weeks to 15 Weeks |
Eligibility | 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 plus disease in any zone) - Written informed consent by parents or legal guardian, according to national requirements Exclusion Criteria: - ROP stage = 3, AP-ROP or suspected AP-ROP, or any other ROP requiring an intervention (study endpoint already reached). - Conditions that indicate open label propranolol such as: thyrotoxicosis, arterial hypertension or certain heart diseases (such as tetralogy of Fallot, paroxysmal supraventricular 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 the aorta, 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 metabolic clearance) - 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 circulatory disturbance), or pheochromocytoma (contraindications for propranolol in adults, not occurring in newborn infants) - Any circumstances that make the investigator believe that participation in the study leads 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 or cardiogenic 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) |
Country | Name | City | State |
---|---|---|---|
Germany | University Hospital Tübingen | Tübingen | Baden-Württemberg |
Switzerland | University Hospital Zurich | Zürich | Zurich |
Turkey | Ankara University School of Medicine Children's Hospital | Ankara |
Lead Sponsor | Collaborator |
---|---|
University of Zurich | Ankara University, University Hospital Tuebingen |
Germany, Switzerland, Turkey,
Buhrer C, Bassler D. Oral Propranolol: A New Treatment for Infants with Retinopathy of Prematurity? Neonatology. 2015;108(1):49-52. doi: 10.1159/000381659. Epub 2015 May 9. — View Citation
Buhrer C, Erdeve O, Bassler D, Bar-Oz B. Oral propranolol for prevention of threshold retinopathy of prematurity (ROPROP): protocol of a randomised controlled trial. BMJ Open. 2018 Jul 6;8(7):e021749. doi: 10.1136/bmjopen-2018-021749. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Intraventricular haemorrhages (all grades) | Intraventricular haemorrhage (all grades) | 48 weeks postmenstrual age | |
Other | Posthaemorrhagic hydrocephalus requiring intervention | Posthaemorrhagic hydrocephalus requiring intervention | 48 weeks postmenstrual age | |
Other | Cystic leukomalacia | Cystic leukomalacia | 48 weeks postmenstrual age | |
Other | Persistent ductus arteriosus requiring treatment | Persistent ductus arteriosus requiring treatment | 48 weeks postmenstrual age | |
Other | Bronchopulmonary dysplasia | Bronchopulmonary dysplasia (mild, moderate, severe), defined and graded according to the consensus statement of the national institutes of health | 48 weeks postmenstrual age | |
Other | Duration of subsequent hospitalisation | Number of days of subsequent hospitalisations | 48 weeks postmenstrual age | |
Other | Duration of primary hospitalisation | Number of days of primary hospitalisation | 48 weeks postmenstrual age | |
Other | Z-scores for weight | Z-scores for weight at the beginning and end of IMP administration | 48 weeks postmenstrual age | |
Other | Z-scores for head circumference | Z-scores for head circumference at the beginning and end of IMP administration | 48 weeks postmenstrual age | |
Other | Duration of supplemental oxygen | Number of days on supplemental oxygen | 48 weeks postmenstrual age | |
Other | Necrotizing enterocolitis | Necrotizing enterocolitis (requiring surgery) | 48 weeks postmenstrual age | |
Other | Safety: Culture-proven sepsis or meningitis during IMP administration | Culture-proven sepsis or meningitis during IMP administration (defined as growth of a recognized pathogen not counting coagulase-negative staphylococci in blood or cerebrospinal fluid in an infant treated for at least 5 d with intravenous antibiotics and a rise of C-reactive protein to more than 10 mg/l during the first 72 h of antibiotic treatment) | 48 weeks postmenstrual age | |
Other | Safety: Symptomatic hypoglycemia during IMP administration | Symptomatic hypoglycemia during IMP administration (blood glucose < 30 mg/dl requiring intravenous glucose administration for 48 h or more), not counting glucose administration "to keep-vein-open" (e.g. at rates of = 1 mL/h) | 48 weeks postmenstrual age | |
Other | Safety: Emergency endotracheal intubation during IMP administration | Emergency endotracheal intubation attributable to obstructive airway disease during IMP administration (excluding elective intubation for surgery) | 48 weeks postmenstrual age | |
Primary | Survival without adverse ophthalmological outcome (stage = 3, AP-ROP, or any ROP treatment) | The primary endpoint for efficacy is survival until 48 weeks postmenstrual age without adverse ophthalmological outcome (stage = 3, AP-ROP, or any ROP treatment) diagnosed according to the International Committee for the Classification of Retinopathy of Prematurity Revisited. | 48 weeks postmenstrual age | |
Secondary | Time to adverse ophthalmological outcome in days | Time to adverse ophthalmological outcome in days (alternative to primary endpoint to account for the timing, considering death as a competing risk) | 48 weeks postmenstrual age | |
Secondary | Survival without adverse ophthalmological outcome | Survival without adverse ophthalmological outcome (as defined for the primary outcome) | 48 weeks postmenstrual age | |
Secondary | Survival with adverse ophthalmological outcome | Survival with adverse ophthalmological outcome (as defined for the primary outcome) | 48 weeks postmenstrual age | |
Secondary | Survival without local treatment for ROP | Survival without local treatment for ROP (ablative laser surgery or intravitreal injections of anti-VEGF agents). | 48 weeks postmenstrual age | |
Secondary | Death until discharge | Death until discharge | 48 weeks postmenstrual age | |
Secondary | Death until 48 weeks postmenstrual age | Death until 48 weeks postmenstrual age | 48 weeks postmenstrual age | |
Secondary | Recurrence of ROP in infants treated with anti-VEGF-antagonists | Recurrence of ROP in infants treated with anti-VEGF-antagonists | 70 (+/- 2 weeks) postmenstrual age | |
Secondary | Need for repeated ROP therapy in infants treated with anti-VEGF-antagonists | Need for repeated ROP therapy in infants treated with anti-VEGF-antagonists | 70 (+/- 2 weeks) postmenstrual age |
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