STOP-ROP--A MULTICENTER TRIAL OF OXYGEN FOR ROP

早产儿视网膜病变（ROP）是一个严重的公共卫生问题 估计有2,060名早产儿出现了严重的视力后遗症， 美国每年有4,400名幸存者， 冷冻疗法。 冷冻疗法并不总是成功的， 视网膜的一部分，其长期后遗症是未知的。 情况 对照研究和轶事报告的治疗ROP与氧气作为 以及在动物模型中进行的研究表明， 在ROP愈合过程中（长达数周）的缺氧可能是一个关键的 决定哪些ROP病例治愈的因素，这一假设得到了 在其他增生性视网膜病变中， 视网膜病变，如糖尿病视网膜病变。 具有讽刺意味的是， 通过给未成熟的婴儿过多的氧气来促进ROP 视网膜导致了严格的氧气管理。 早产儿 不稳定的心肺状态和最低的氧气水平 给药可经历间歇性缺氧， 高血压和肺心病。 在实践中，氧气被给予更多 一旦这些婴儿的视网膜完全 血管化，因此没有ROP的风险。 这些数据证明 对“补充治疗用氧 阈值前ROP（STOP-ROP）将使 婴儿进展到阈值ROP。" 本提案是该测试的主要申请， 《程序手册》以及协调和 参与中心。 发生阈值前ROP（定义为 在CRYO-ROP研究中）将接受持续的氧饱和度 监测，并随机分配氧气管理在两个 规定的氧气水平，常规（脉搏血氧饱和度为89-94% 饱和度）与补充（脉搏血氧饱和度为96-99%）。 主 结果变量将是进展到 阈值ROP。 预计样本量为880， 在15-30家临床试验机构中进行为期一年的入组;将进行中期分析。 将收集关于特定眼科、新生儿和成本结局的数据 前瞻性地通过3个月校正胎龄。 如果这种 治疗被证明是有效和安全的，婴儿中度 ROP阈值前（每年近5000人）将从其使用中受益， 在眼科和新生儿的结果。

Retinopathy of Prematurity (ROP) remains a serious public health problem causing significant visual sequelae in an estimated 2,060 premature survivors per year in the United States or 4,400 without the benefits of Cryotherapy. Cryotherapy is not always successful, ablates a significant portion of the retina, and its long term sequelae are unknown. Case control studies and anecdotal reports of treatment of ROP with oxygen as well as studies conducted in an animal model demonstrate that chronic (weeks-long) hypoxia during the ROP healing process may be a critical factor in determining which cases of ROP heal, an hypothesis supported by the association with retinal hypoxia in other proliferative retinopathies, such as diabetic retinopathy. Ironically, concerns over precipitating ROP by giving too much oxygen to infants with immature retinae has lead to strict oxygen management. Premature infants with unstable cardiopulmonary status and this minimal level of oxygen administration can experience episodic hypoxia leading to pulmonary hypertension and cor pulmonale. In practice, oxygen is given more liberally to these infants as soon as their retinae become fully vascularized, and thus free from the risk of ROP. These data justify testing of the hypothesis that "Supplemental Therapeutic Oxygen for Prethreshold ROP (STOP-ROP) will reduce by at least 1/3 the number of infants progressing to Threshold ROP." This proposal is the Lead Application for that test and is submitted with the Manual of Procedures, and proposals from the Coordinating and Participating Centers. Infants who develop Prethreshold ROP (as defined in the CRYO-ROP study) will receive continuous oxygen saturation monitoring, and randomly assigned oxygen administration at one of two specified oxygen levels, conventional (pulse oximetry of 89-94% saturation) vs supplemental (pulse oximetry of 96-99%). The primary outcome variable will be the proportion of infants who progress to Threshold ROP. The projected sample size of 880 is compatible with a 3 year enrollment in 15-30 centers; interim analyses will be conducted. Data on specific ophthalmic, neonatal and cost outcomes will be collected prospectively through 3 months corrected gestational age. Should this treatment prove to be both efficacious and safe, infants with moderate ROP prethreshold (nearly 5000 each year) would benefit from its use, both in their ophthalmic and neonatal outcomes.