Safety and Efficacy of Propranolol Treatment in Newborns With Retinopathy of Prematurity:a Prospective Cohort Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 100
- 主要终点
- Number of newborns who need surgical treatment
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of oral/local propranolol in preterm newborns who diagnosed as early phase of retinopathy of prematurity (ROP).
详细描述
The incidence of Retinopathy of Prematurity (ROP) in preterm newborns less than 1500g is about 60% in the developed countries around the world, while there are much more preterm newborns more than 1500g and 32 weeks gestational age with Retinopathy of Prematurity (ROP) had to be treated in the developing countries. ROP has listed top of the five causes lead to blindness in children, which seriously threated children's vision and quality of life.
The ablation of the retina with photocoagulation by laser or cryotherapy reduces the incidence of blindness by suppressing the neovascular phase of ROP. However, those Surgeries require anesthesia and some of them may result in complications such as apnea, neonatal necrotizing enterocolitis, sepsis, and hemorrhage of digestive tract. As a result, it's important to study an alternative non-surgical treatment method.
The development of ROP depends largely from vascular endothelial growth factor (VEGF). The reduction of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP.
Propranolol is a kind of beta-adrenergic receptor (β-AR) which can inhibit the expression of VEGF and has been first choice of treating infantile hemangioma, the most common tumor of infancy. There are some pilot studies suggesting that the administration of oral propranolol is effective in counteracting the progression of ROP in patients without operation indication. Nevertheless that safety is a concern, for oral propranolol may result in associated complications and side effects such as bradycardia, hypotension, injury of cerebrum growth and olfactory.
Recently a research of eye drop propranolol in a mouse model of oxygen-induced retinopathy (OIR) has shown that propranolol was still effective in inhibiting angiogenic processes, indicating that local administration is equally effective.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- — 至 8 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Preterm newborns (birth weight less than 1500g) with stage 1/2 ROP in Zone 2 or 3 without plus
- •A signed parental informed consent
排除标准
- •Newborns with heart failure
- •Newborns with recurrent bradycardia (heart rate < 90 beat per minute)
- •Newborns with second or third degree atrioventricular block
- •Newborns with congenital cardiovascular anomalies, except for persistent ductus arteriosus, patent foramen ovale and small ventricular septal defects
- •Newborns with hypotension
- •Newborns with renal failure
- •Newborns with actual cerebral haemorrhage
- •Newborns with other diseases which contraindicate the use of beta-adrenoreceptor blockers.
- •Newborns with a more severe stage of ROP than stage 2 or in Zone 1
研究组 & 干预措施
oral propranol group
Enrolled preterm newborns will receive oral propranolol 0.25mg/kg daily(every 24 hours).
The treatment will be started as soon as the diagnosis of stage 1 or 2 ROP without plus is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days.
干预措施: Propranolol (Drug)
oral placebo group
Enrolled preterm newborns will receive oral normal saline 0.25mg/kg daily(every 24 hours) and other disposals will be done similarily to the oral propranol group.
干预措施: placebo (Drug)
eye drop propranol group
Enrolled preterm newborns will receive propranolol as ophthalmic solution (0.2%). 3 microdrops of 6 microliters (μL) propranolol solution (= 6 μg propranolol/microdrop) will be topically applied with a calibrated pipette,in each eye, four times daily (every 6 hours) .
The treatment will be started as soon as the diagnosis of stage 1 or 2 ROP without plus is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days.
干预措施: Propranolol (Drug)
eye drop placebo group
Enrolled preterm newborns will receive placebo as ophthalmic solution in the same way of eye drop propranolol and other disposals will be done similarily to the eye drop propranol group.
干预措施: placebo (Drug)
结局指标
主要结局
Number of newborns who need surgical treatment
时间窗: participants will be followed for the duration of hospital stay, an expected average of 2 months
Plasma concentrations of propranolol at the steady state measured by dried blood spots
时间窗: 10th day of treatment
Number of newborns who have ROP progression
时间窗: participants will be followed for the duration of hospital stay, an expected average of 2 months
Number of newborns who have side effects
时间窗: participants will be followed for the duration of hospital stay, an expected average of 2 months
次要结局
- visual assessment of enrolled newborns(about 12 months)
- Scores of Gesell development scale of enrolled newborns(about 12 months)
研究者
Nie Chuan
Vice director of Department of Neonatology
Guangdong Women and Children Hospital