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| ID | Type | Description | Link |
|---|---|---|---|
| 32ER30_173677 | Other Grant/Funding Number | Swiss National Science Foundation (SNSF) | |
| 2017-002124-24 | EudraCT Number |
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| Name | Class |
|---|---|
| Ankara University | OTHER |
| University Hospital Tuebingen | OTHER |
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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.
Threshold Retinopathy of Prematurity (ROP), observed in a fraction of extremely premature infants, is characterized by retinal vessel proliferation that threatens vision secondary to retinal detachment. Currently available treatments (ablative laser surgery or intravitreal anti-VEGF injections) may prevent most but not all cases of permanent ROP-mediated blindness and are associated with significant costs and side effects.
Orally administered propranolol, a commonly used drug to treat hypertension, may be effective in halting progression of ROP to severe stages, as suggested by preliminary data from small studies. Propranolol has been used for decades not only in adult patients but also in newborn infants with heart diseases. Moreover, it has been licensed in 2014 for the use in newborn infants with hemangioma in the European Union, Switzerland and the United States. This multicenter randomized placebo-controlled trial aims to assess whether oral propranolol given to extremely premature infants below 28 weeks gestational age reduces the rates of threshold ROP.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propranolol | Experimental | Oral propranolol (1.6 mg propranolol-HCl/kg/d in 3-4 divided dosages) given for a maximum of 10 weeks (depending on postmenstrual gestational age at birth) |
|
| Placebo | Placebo Comparator | Placebo (same duration as oral propranolol solution) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol | Drug | Oral propranolol (1.6 mg propranolol-hydrochloride/kg/d in 4 divided dosages) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Survival without adverse ophthalmological outcome |
| Measure | Description | Time Frame |
|---|---|---|
| Intraventricular haemorrhages (all grades) | Intraventricular haemorrhage (all grades) | 48 weeks postmenstrual age |
| Posthaemorrhagic hydrocephalus requiring intervention | Posthaemorrhagic hydrocephalus requiring intervention |
Inclusion criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Dirk Bassler, M.D. | Contact | +41 44 255 53 40 | dirk.bassler@usz.ch | |
| Christoph Rüegger, M.D. | Contact | +41 43 253 98 10 | christoph.rueegger@usz.ch |
| Name | Affiliation | Role |
|---|---|---|
| Dirk Bassler, M.D. | University of Zurich | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Tübingen | Recruiting | Tübingen | Baden-Wurttemberg | 72076 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25968340 | Result | 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. | |
| 29982217 | Result | 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. |
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Anonymized data set containing gestational age (only weeks), birth weight (in 100g categories), year of birth, country, gender, intervention (propranolol or placebo), outcome (retinopathy of prematurity, maximum stage), date and type of treatment for retinopathy if any
6 months - 5 years after publication of the results in a peer-reviewed journal
Investigators whose proposed use of the data has been approved by an independent review committee (learned intermediary)
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| ID | Term |
|---|---|
| D012178 | Retinopathy of Prematurity |
| ID | Term |
|---|---|
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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Double-blind Placebo-controlled
| Placebo | Drug | Oral solution containing the same excipients as propranolol solution |
|
Survival without adverse ophthalmological outcome (as defined for the primary outcome) |
| 48 weeks postmenstrual age |
| Survival with adverse ophthalmological outcome | Survival with adverse ophthalmological outcome (as defined for the primary outcome) | 48 weeks postmenstrual age |
| 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 |
| Death until discharge | Death until discharge | 48 weeks postmenstrual age |
| Death until 48 weeks postmenstrual age | Death until 48 weeks postmenstrual age | 48 weeks postmenstrual age |
| 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 |
| 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 |
| 48 weeks postmenstrual age |
| Cystic leukomalacia | Cystic leukomalacia | 48 weeks postmenstrual age |
| Persistent ductus arteriosus requiring treatment | Persistent ductus arteriosus requiring treatment | 48 weeks postmenstrual age |
| 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 |
| Duration of subsequent hospitalisation | Number of days of subsequent hospitalisations | 48 weeks postmenstrual age |
| Duration of primary hospitalisation | Number of days of primary hospitalisation | 48 weeks postmenstrual age |
| Z-scores for weight | Z-scores for weight at the beginning and end of IMP administration | 48 weeks postmenstrual age |
| Z-scores for head circumference | Z-scores for head circumference at the beginning and end of IMP administration | 48 weeks postmenstrual age |
| Duration of supplemental oxygen | Number of days on supplemental oxygen | 48 weeks postmenstrual age |
| Necrotizing enterocolitis | Necrotizing enterocolitis (requiring surgery) | 48 weeks postmenstrual age |
| 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 |
| 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 |
| 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 |
| University Hospital Zurich | Recruiting | Zurich | Canton of Zurich | 8091 | Switzerland |
|
| Ankara University School of Medicine Children's Hospital | Recruiting | Ankara | Ankara | 06590 | Turkey (Türkiye) |
|
| D009358 |
| Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |