Howard Richard F, Radic Tatjana, Sohns Melanie, Eerdekens Mariëlle, Waßmuth Andrea
Department of Anaesthesia and Pain Medicine, Great Ormond Street Hospital and the GOS-UCL Institute of Child Health, London, UK.
Grünenthal GmbH, Aachen, Germany.
J Pain Res. 2020 Nov 30;13:3157-3170. doi: 10.2147/JPR.S272751. eCollection 2020.
Investigation of the efficacy and safety of tapentadol prolonged release (PR) compared with morphine PR for long-term treatment of pain in children.
Children aged 6 to <18 years requiring long-term treatment with opioids were studied in a 12-month, 2-part, multi-center trial: Part 1, 14-day open-label, randomized, active-controlled, parallel group non-inferiority trial comparing twice daily tapentadol PR with morphine PR; Part 2, open-label treatment with tapentadol PR for up to 12 months or no treatment "safety observation period". Pain intensity was rated with visual analogue scale or Faces Pain Scale-Revised, and non-inferiority was assessed by comparison of "treatment responders" (those completing the 14-day treatment period and showing pre-defined changes in pain rating) in each group.
Twenty-three of 48 centers enrolled 73 patients. In Part 1, 45 and 24 patients received tapentadol or morphine, respectively, of which 40 and 22 completed 14-day treatment. In Part 2, thirty-six and 58 patients entered the tapentadol PR or observation periods, respectively, with 20/36 completing at least 12 weeks of treatment; 10 of the 36 had received morphine in Part 1. Forty-four of the 58 patients in the safety observation period had received tapentadol. Tapentadol PR was non-inferior to morphine PR (lower limit of confidence interval above negative non-inferiority margin of -0.2) in Part 1. Rates of adverse events were as expected with nausea (22.2%) and constipation (15.6%) in the tapentadol PR group, and with vomiting (33.3%), nausea and constipation (each 16.7%) in the morphine PR group. No new safety issues were identified; the safety profile of tapentadol over the 12 months treatment and observation periods was comparable to that established in subjects >18 years old.
Tapentadol PR was well tolerated and equivalent to morphine PR for both efficacy and safety in children (6 to <18 years old) requiring long-term treatment with opioids.
比较曲马多缓释片（PR）与吗啡PR用于儿童长期疼痛治疗的疗效和安全性。
在一项为期12个月的两部分多中心试验中，对6至<18岁需要长期使用阿片类药物治疗的儿童进行研究：第1部分，为期14天的开放标签、随机、活性对照、平行组非劣效性试验，比较每日两次的曲马多PR与吗啡PR；第2部分，使用曲马多PR进行长达12个月的开放标签治疗或不进行治疗的“安全性观察期”。疼痛强度采用视觉模拟量表或面部疼痛量表修订版进行评分，并通过比较每组中的“治疗反应者”（即完成14天治疗期并在疼痛评分上显示出预先定义变化的患者）来评估非劣效性。
48个中心中的23个中心招募了73名患者。在第1部分中，分别有45名和24名患者接受了曲马多或吗啡治疗，其中40名和22名完成了14天的治疗。在第2部分中，分别有36名和58名患者进入曲马多PR治疗期或观察期，其中20/36名完成了至少12周的治疗；36名中的10名在第1部分中接受过吗啡治疗。安全观察期的58名患者中有44名接受过曲马多治疗。在第1部分中，曲马多PR不劣于吗啡PR（置信区间下限高于-0.2的非劣效性负界值）。曲马多PR组不良事件发生率与预期一致，恶心发生率为22.2%，便秘发生率为15.6%；吗啡PR组呕吐发生率为33.3%，恶心和便秘发生率均为16.7%。未发现新的安全问题；曲马多在12个月治疗和观察期内的安全性概况与18岁以上受试者中确立的情况相当。
对于需要长期使用阿片类药物治疗的儿童（6至<18岁），曲马多PR耐受性良好，在疗效和安全性方面与吗啡PR相当。
