Oral Propranolol for the Prevention of High-Grade Retinopathy of Prematurity
Résumé de l'étude
In extremely preterm infants (<28 weeks of gestation [WG]), retinopathy of prematurity (ROP) can develop between 30 and 36 WG. ROP is associated with various visual impairments, blindness, and poorer long-term neuromotor development. The blood vessels of the retina are still poorly developed in extremely preterm infants and only reach their final size and functionality about 4-8 weeks before birth. In a few rare preterm infants, the vessel growth occurs excessively during this phase and can, in the worst case, lead to retinal detachment and even blindness. About one in a hundred of these extremely preterm infants is affected. Currently, ROP can be treated with laser beams or with antibodies injected into the eyeball against the vascular growth factor. Both treatments are expensive and show side effects (Laser: focal destruction of the retina with scarring and consequent visual field loss, antibody injection: recurrent growth of blood vessels, unclear impact on neuromotor development). Many, but not all cases of ROP-related blindness can be avoided with one of these two treatments. On the other hand, it is shown that ROP treatment is often associated with impaired neuromotor development at ages 2, 5, and 11 years. The search for evidence of a safe intervention to protect against severe ROP should continue with this study. The present study is an international multicenter study conducted double-blind (neither the doctor nor the parents know whether the child receives the medication or a placebo). Patients are randomly assigned to the treatment group (receives study medication) or the control group (receives placebo).
(BASEC)
Intervention étudiée
Eligible preterm infants will receive oral propranolol or placebo 3-4 times daily for a maximum of 10 weeks (or until discharge). The starting dose is 0.4 mg/kg/day and will be increased to 1.6 mg/kg/day within 3 days. Before discharge, the medication will be reduced by 50% for one day and then discontinued the following day. Medication intake may be interrupted or stopped based on defined criteria. No medication will be administered to discharged children.
(BASEC)
Maladie en cours d'investigation
Retinopathy of Prematurity (ROP) in extremely preterm infants (< 28 WG) with early ROP stage 1 or 2 at ages 31-37 WG.
(BASEC)
• Preterm infants born before 28 weeks of gestation with weight < 1250 g • at least 5 weeks old • postmenstrual gestational age at inclusion 31-37 weeks of gestation • diagnosed retinopathy of prematurity grade 1 or 2 (BASEC)
Critères d'exclusion
• diagnosed retinopathy of prematurity grade 3 • Congenital malformation that contraindicates the use of propranolol • Large hemangiomas (BASEC)
Lieu de l’étude
Bâle, Berne, Lausanne, St-Gall, Zurich
(BASEC)
Sponsor
University of Zurich
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Dr. Christoph Rüegger
043 253 98 10
christoph.rueegger@clutterusz.chUniversity of Zurich / University hospital of Zurich
(BASEC)
Informations générales
University of Zurich,
+41 44 255 53 40
christoph.rueegger@clutterusz.ch(ICTRP)
Informations scientifiques
University of Zurich,
+41 44 255 53 40
christoph.rueegger@clutterusz.ch(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale de Zurich
(BASEC)
Date d'approbation du comité d'éthique
09.01.2019
(BASEC)
Identifiant de l'essai ICTRP
NCT03083431 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
Oral propranolol for prevention of threshold retinopathy of prematurity (BASEC)
Titre académique
Oral Propranolol for Prevention of Threshold Retinopathy of Prematurity (ICTRP)
Titre public
Oral Propranolol for Prevention of Threshold Retinopathy of Prematurity (ICTRP)
Maladie en cours d'investigation
Retinopathy of Prematurity (ICTRP)
Intervention étudiée
Drug: Propranolol;Drug: Placebo (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Critères d'inclusion/exclusion
Gender: All
Maximum age: 15 Weeks
Minimum age: 5 Weeks
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 ?mol/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) (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Survival without adverse ophthalmological outcome (stage = 3, AP-ROP, or any ROP treatment) (ICTRP)
Time to adverse ophthalmological outcome in days;Survival without adverse ophthalmological outcome;Survival with adverse ophthalmological outcome;Survival without local treatment for ROP;Death until discharge;Death until 48 weeks postmenstrual age;Recurrence of ROP in infants treated with anti-VEGF-antagonists;Need for repeated ROP therapy in infants treated with anti-VEGF-antagonists (ICTRP)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
Ankara University;University Hospital Tuebingen (ICTRP)
Contacts supplémentaires
Dirk Bassler, M.D.;Dirk Bassler, M.D., dirk.bassler@usz.ch, +41 44 255 53 40, University of Zurich, (ICTRP)
ID secondaires
32ER30_173677, 2017-002124-24, RoProp (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT03083431 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible