Study protocol: safety and efficacy of propranolol in newborns with Retinopathy of Prematurity (PROP-ROP): ISRCTN18523491

Abstract

BackgroundDespite 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/DesignPreterm 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.DiscussionThis 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.Trial RegistrationCurrent Controlled Trials ISRCTN18523491; ClinicalTrials.gov Identifier NCT01079715; EudraCT Number 2010-018737-21

Systemic Beta-Blockers May Reduce the Need for Repeated Intravitreal Injections in Patients With Wet Age-Related Macular Degeneration Treated by Bevacizumab

“…20 Systemic BABA are frequently used in the clinical practice to treat cardiac arrhythmia, hypertension, migraine, and hyperthyroidism among other conditions. Propanolol has been used to treat neovascular conditions such as infantile capillary hemangiomas [21][22][23][24][25][26][27][28][29][30][31] and retinopathy of prematurity 32 ; clinical trials are underway to elucidate the effect of these therapies.…”

Retinopathy of Prematurity

“…163 Additional studies to assess the best choice of anti-VEGF drug, the optimum dose, the pharmacokinetics, and short-term and long-term safety are warranted. 164,165 The β blocker propranolol has been proposed as a potential treatment to reduce retinal neovascularisation 166 and clinical studies are underway in Israel (NCT01238471) and Italy (NCT01079715). However, investigators of a 2012 study 167 report that propranolol does not reduce retinopathy in a mouse model of retinopathy of prematurity.…”

Pathogenesis and Management of Retinopathy of Prematurity in Premature Infants

“…30 The Propranolol in Newborns with Retinopathy of Prematurity (PROP-ROP) clinical trial is currently underway to evaluate the effectiveness of propranolol in infants with stage 2 ROP in zone II/III without plus disease. 31 The primary goal of this study is to evaluate the safety of the drug including side effects such as bradycardia, hypoglycemia, hypotension and dyslipidemia.…”