Du Lizhong, Tong Xiaomei, Chen Chao, Gao Xirong, Gagnatelli Alessandra, Li Jingyang, Santoro Debora, Nicolardi Sara, Fabbri Laura
Neonatal Intensive Care Unit, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Peking University Third Hospital, Beijing, China.
Front Pediatr. 2020 Mar 11;8:76. doi: 10.3389/fped.2020.00076. eCollection 2020.
Caffeine citrate has been approved in China for the management of apnea of prematurity. This clinical trial was conducted as a condition of regulatory approval. The aim was to confirm the efficacy of caffeine citrate in the treatment of recurrent intermittent hypoxia and bradycardia in preterm newborns with primary apnea. The primary outcome was the change from baseline in the number of apnea events after loading dose administration of caffeine citrate. Secondary efficacy outcomes included the change from baseline in apnea events after 2 and 4 weeks of maintenance doses. This was a multicenter, prospective longitudinal open-label, single-arm study. Neonates who had experienced at least four apnea events during a 24 h period received a loading dose of caffeine citrate 20 mg/kg; those who required additional maintenance doses received 5 mg/kg/day (titrated up to 10 mg/kg/day in case of insufficient response). The number of apnea events was recorded for 6-12 h prior to the loading dose (baseline), and for 12 h post-dose, following the loading dose and at Weeks 2 and 4 (during maintenance). A total of 247 neonates received the loading dose, who had a significant reduction from baseline of 3.9 events (p < 0.001) in the mean number of apnea events. The subset of neonates who required maintenance doses also had significant reductions in the number of events at all visits (p < 0.001 for all). A total of 79.4% of participants had at least one adverse event, but only one non-serious and no serious events were considered related to treatment. In this large, prospective, open-label study, premature infants with a history of apnea who received caffeine citrate were significantly less likely to experience further apnea events.
枸橼酸咖啡因在中国已被批准用于治疗早产儿呼吸暂停。本临床试验是作为监管批准的条件而进行的。目的是确认枸橼酸咖啡因治疗原发性呼吸暂停的早产儿反复间歇性缺氧和心动过缓的疗效。主要结局是枸橼酸咖啡因负荷剂量给药后呼吸暂停事件数量相对于基线的变化。次要疗效结局包括维持剂量2周和4周后呼吸暂停事件相对于基线的变化。这是一项多中心、前瞻性纵向开放标签单臂研究。在24小时内经历至少4次呼吸暂停事件的新生儿接受20mg/kg的枸橼酸咖啡因负荷剂量；那些需要额外维持剂量的新生儿接受5mg/kg/天（如果反应不足可滴定至10mg/kg/天）。在负荷剂量前6 - 12小时（基线）、负荷剂量后12小时、负荷剂量后以及第2周和第4周（维持期间）记录呼吸暂停事件的数量。共有247名新生儿接受了负荷剂量，其呼吸暂停事件的平均数量较基线显著减少了3.9次（p < 0.001）。需要维持剂量的新生儿亚组在所有访视时呼吸暂停事件数量也显著减少（所有p < 0.001）。共有79.4%的参与者至少发生了一次不良事件，但只有1例非严重不良事件且无严重不良事件被认为与治疗有关。在这项大型、前瞻性、开放标签研究中，有呼吸暂停病史的早产儿接受枸橼酸咖啡因后发生进一步呼吸暂停事件的可能性显著降低。
