title: Study protocol: safety and efficacy of propranolol in newborns with Retinopathy of Prematurity (PROP-ROP): ISRCTN18523491.
abstract: BACKGROUND
  Despite new therapeutic approaches have improved the prognosis of newborns with retinopathy of prematurity (ROP), an unfavourable structural and functional outcome still remains high. There is high pressure to develop new drugs to prevent and treat ROP. There is increasing enthusiasm for anti-VEGF drugs, but angiogenic inhibitors selective for abnormal blood vessels would be considered as an optimal treatment.In an animal experimental model of proliferative retinopathy, we have recently demonstrated that the pharmacological blockade of beta-adrenoreceptors improves retinal neovascularization and blood retinal barrier breakdown consequent to hypoxia. The purpose of this study is to evaluate the propranolol administration in preterm newborns suffering from a precocious phase of ROP in terms of safety and efficacy in counteracting the progression of retinopathy.
  
  
  METHODS
  Preterm newborns (gestational age at birth lower than 32 weeks) with stage 2 ROP (zone II-III without plus) will be randomized, according to their gestational age, to receive propranolol added to standard treatment (treatment adopted by the ETROP Cooperative Group) or standard treatment alone. Propranolol will be administered until retinal vascularization will be completely developed, but not more than 90 days. Forty-four participants will be recruited into the study. To evaluate the safety of propranolol administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of propranolol, the progression of the disease, the number of laser treatments or vitrectomies, the incidence of retinal detachment or blindness, will be evaluated by serial ophthalmologic examinations. Visual function will be evaluated by means of behavioural standardized tests.
  
  
  CONCLUSIONS
  This pilot study is the first research that explores the possible therapeutic role of beta blockers in ROP. The objective of this research is highly ambitious: to find a treatment simple, inexpensive, well tolerated and with few adverse effects, able to counteract one of the major complications of the prematurity. Any favourable results of this research could open new perspectives and original scenarios about the treatment or the prevention of this and other proliferative retinopathies.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN18523491; ClinicalTrials.gov Identifier NCT01079715; EudraCT Number 2010-018737-21.
authors.affiliation: Neonatal Intensive Care Unit, Department of Perinatal Medicine, A, Meyer University Children's Hospital, Florence, Italy. l.filippi@meyer.it
authors.forename: Luca
authors.initials: L
authors.lastname: Filippi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cavallaro
authors.forename: Patrizio
authors.initials: P
authors.lastname: Fiorini
authors.forename: Marta
authors.initials: M
authors.lastname: Daniotti
authors.forename: Valentina
authors.initials: V
authors.lastname: Benedetti
authors.forename: Gloria
authors.initials: G
authors.lastname: Cristofori
authors.forename: Gabriella
authors.initials: G
authors.lastname: Araimo
authors.forename: Luca
authors.initials: L
authors.lastname: Ramenghi
authors.forename: Agostino
authors.initials: A
authors.lastname: La Torre
authors.forename: Pina
authors.initials: P
authors.lastname: Fortunato
authors.forename: Liliana
authors.initials: L
authors.lastname: Pollazzi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.forename: Paola
authors.initials: P
authors.lastname: Bagnoli
authors.forename: Chiara
authors.initials: C
authors.lastname: Ristori
authors.forename: Massimo
authors.initials: M
authors.lastname: Dal Monte
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bilia
authors.forename: Benedetta
authors.initials: B
authors.lastname: Isacchi
authors.forename: Sandra
authors.initials: S
authors.lastname: Furlanetto
authors.forename: Francesca
authors.initials: F
authors.lastname: Tinelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cioni
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Donzelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Osnaghi
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D010865:Pilot Projects; D011433:Propranolol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012178:Retinopathy of Prematurity / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D042262:Retinoscopy; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol