Clinical Trial: Oral Propranolol Versus Placebo for Early Stages of Retinopathy of Prematurity: A Randomized and Prospective Study
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Oral Propranolol Versus Placebo for Early Stages of Retinopathy of Prematurity (ROP): A Pilot, Randomized and Prospective Study.
Brief Summary: In premature infants, propranolol (Prop) treatment might suppress continuing neo-vascularization (NV) and decelerate the progression of retinopathy of prematurity (ROP) towards its severe stages (III-V), thus avoiding the need of interventions (CRYO and/or LASER photo-coagulation of the ischemic retina and preventing severe ocular sequelae. We therefore plan to prospectively investigate the influence of prop versus placebo in VLBW infants with ROP stage 1 (zone I), with stage 2 or higher (any zone) or with Plus disease, along with close follow up regarding safety of prop administration and its effect on ROP.
Detailed Summary:
Retinopathy of prematurity (ROP) affects the retinal microvasculature, mostly of very-low-birth-weight (VLBW: < 1500g) premature infants, and is a significant complication of extreme prematurity leading sometimes to devastating consequences. Although ROP is usually mild with no harm, it happens not very rarely to be aggressive causing neo-vascularization (NV) in the immature retina that at times can progress to severe fibrovascular proliferation, retinal detachment and blindness (1). Major risk factors for ROP are low gestational age, low birth weight, hyperoxia, respiratory distress syndrome (RDS) and intraventricular hemorrhage (IVH) (2) as well as postnatal steroid therapy (3). Of note is one report showing that the use of beta-blocking agents by the mother before birth was found to be associated with the development of ROP (4). However, so far no one reported a similar effect of the postnatal use of beta blockers on ROP.
The incidence of ROP is inversely related to gestational age (GA) and birth weight (BW). The condition develops in 51% of infants with a birth weight (BW) <1700 g (5). In infants weighing less than 1250 g, 50% show some evidence of ROP and 10% progress to stage III ROP. According to the Israeli VLBW-Database in 2007, 23.9% of infants develop ROP (all stages), while 4.8% develop severe ROP (stage III-IV) (4). Worldwide, at least 50,000 children are blind from ROP (2,7). In South Africa it accounts for 10.6% of cases of childhood blindness (8). In the US, annually, 500-700 children become blind due to ROP, and 2100 infants will be affected by cicatricial sequelae, such as myopia, strabismus, as well as late-onset retinal detachment (1).
LASER photocoagulation of the ischemic retina is the therapy of choice for moderate to severe ROP and is required in 19.8%, 7.7%. 1.5% and 0.6% of infants weighing
Sponsor: Rambam Health Care Campus
Current Primary Outcome: Regression of Retinopathy of Prematurity (ROP) in Premature Infants by Propranolol Therapy [ Time Frame: propranolol therapy for up 4 weeks ]
If ROP regresses without the need for treatment (laser and/or CRYO), this will be considered a favorable outcome. On the other hand, if ROP progresses to require treatment, it will be regarded as an unfavorable outcome.
Evidence for regression of ROP was observed by serial retinal examinations performed by ophthalmologists as well as by reduction for the need of invasive interventions such as laser photocoagulation of disease areas in the retina.
Original Primary Outcome: Regression of ROP in premature infants by propranolol therapy [ Time Frame: propranolol therapy for up 4 weeks ]
Current Secondary Outcome: Safety of Propranolol Therapy in Premature Infants [ Time Frame: 4 weeks of propranolol therapy in premature infants ]
Original Secondary Outcome: Same as current
Information By: Rambam Health Care Campus
Dates:
Date Received: November 8, 2010
Date Started: May 2010
Date Completion:
Last Updated: June 12, 2014
Last Verified: June 2014
