Department of Pediatrics, The Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA.
Tufts Clinical and Translational Science Institute, Tufts University, and the Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA.
Pediatr Res. 2019 Aug;86(2):254-260. doi: 10.1038/s41390-019-0419-3. Epub 2019 May 13.
Preterm neonates can develop chronic pulmonary insufficiency of prematurity (CPIP) later in infancy. Recombinant human CC10 protein (rhCC10) is an anti-inflammatory agent that could potentially prevent CPIP.
The safety and efficacy of a single intratracheal dose of rhCC10 in reducing CPIP at 12 months corrected gestational age (CGA) was evaluated in a Phase II double-blind, randomized, placebo-controlled, multisite clinical trial. Eighty-eight neonates were randomized: 22 to placebo and 22 to 1.5 mg/kg rhCC10 in the first cohort and 21 to placebo and 23 to 5 mg/kg rhCC10 in the second cohort. Neonates were followed to 12 months CGA.
With CPIP defined as signs/symptoms, medical visits, hospital readmissions, and use of medications for respiratory complications at 12 months CGA, no significant differences were observed between rhCC10 or placebo groups. Only 5% of neonates had no evidence of CPIP at 12 months CGA.
A single dose of rhCC10 was not effective in reducing CPIP at 12 CGA. Since most neonates had evidence of CPIP using these exploratory endpoints, it is essential to develop more robust outcome measures for clinical trials of respiratory medications in high-risk premature neonates.
早产儿在婴儿期后可能会发展为慢性肺不成熟（CPIP）。重组人 CC10 蛋白（rhCC10）是一种抗炎药，有可能预防 CPIP。
在一项 II 期双盲、随机、安慰剂对照、多中心临床试验中，评估了单次气管内给予 rhCC10 剂量以减少 12 个月校正胎龄（CGA）时 CPIP 的安全性和有效性。88 名新生儿随机分组：22 名接受安慰剂，22 名接受 1.5mg/kg rhCC10 作为第一队列，21 名接受安慰剂，23 名接受 5mg/kg rhCC10 作为第二队列。新生儿随访至 12 个月 CGA。
CPIP 定义为 12 个月 CGA 时的体征/症状、医疗就诊、住院再入院和因呼吸并发症使用药物，rhCC10 或安慰剂组之间无显著差异。只有 5%的新生儿在 12 个月 CGA 时没有 CPIP 的证据。
单次剂量的 rhCC10 不能有效减少 12 个月 CGA 时的 CPIP。由于使用这些探索性终点，大多数新生儿都有 CPIP 的证据，因此对于高危早产儿呼吸药物临床试验，开发更强大的结局测量方法至关重要。
