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口服普萘洛尔治疗婴幼儿血管瘤的随机对照试验
A Randomized, Controlled Trial of Oral Propranolol in Infantile Hemangioma


Christine Léauté-Labrèze ... 肿瘤 妇产科和儿科 • 2015.02.19

普萘洛尔治疗重症婴儿血管瘤:剂量和疗程已定

 

李丽,马琳*

首都医科大学附属北京儿童医院皮肤科

*通讯作者

 

婴儿血管瘤是儿童最常见的皮肤良性肿瘤之一。尽管大部分瘤体可在几年后自行消退,但发生在口腔、眼、鼻、气道等特殊部位及全身大面积、多发的一些重症血管瘤却可以引起严重的并发症,导致毁形、功能损害甚至危及生命。而且未经治疗的瘤体消退后,有25%~69%的患儿残存皮肤及皮下组织退行性改变,包括瘢痕、萎缩、色素减退、毛细血管扩张和皮肤松弛。因此,对于婴儿血管瘤尤其是重症血管瘤进行早期干预治疗是非常重要的。

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摘要


背景

尽管来自随机对照试验的相关使用数据有限,口服普萘洛尔已被用于治疗复杂的婴幼儿血管瘤。

 

方法

我们进行了一项多中心、随机、双盲、适应性的2~3期临床试验,评估一种儿科特异性普萘洛尔口服液对患有需要全身治疗的增生性婴幼儿血管瘤的1~5月龄婴儿的疗效和安全性。患儿被随机分配接受安慰剂或4种普萘洛尔方案中的一种(1 mg/[kg·d]或3 mg/[kg·d]的普萘洛尔碱,持续3或6个月)。研究中进行了预先计划的中期分析以确定用于分析最终疗效的给药方案。主要是24周时试验治疗成功(目标血管瘤完全或几乎完全消退)或失败,评估方法为对标准化照片进行独立、集中的盲法评估。

 

结果

在接受了随机分配的460名婴儿中,有456名接受了治疗。对完成了24周试验治疗的前188名患者进行了中期分析,并据此选择用于最终疗效分析的方案为普萘洛尔3 mg/(kg·d),持续治疗6个月。该方案的治疗成功率高于安慰剂组(60% vs. 4%,P<0.001)。接受了该普萘洛尔方案的患者中有88%在第5周时表现出改善,而接受安慰剂的患者中只有5%表现出改善。普萘洛尔治疗成功的患儿中有10%需要在随访期间进行全身再治疗。已知与普萘洛尔相关的不良事件(低血糖、低血压、心动过缓和支气管痉挛)发生较少,在安慰剂组和普萘洛尔组中的发生率无显著性差异。

 

结论

该试验表明普萘洛尔可有效治疗婴幼儿血管瘤,其剂量为3 mg/(kg·d),持续6个月(本研究由Pierre Fabre Dermatologie资助;在ClinicalTrials.gov上的编号为NCT01056341)。





作者信息

Christine Léauté-Labrèze, M.D., Peter Hoeger, M.D., Juliette Mazereeuw-Hautier, M.D., Laurent Guibaud, M.D., Eulalia Baselga, M.D., Gintas Posiunas, M.D., Ph.D., Roderic J. Phillips, M.D., Hector Caceres, M.D., Juan Carlos Lopez Gutierrez, M.D., Rosalia Ballona, M.D., Sheila Fallon Friedlander, M.D., Julie Powell, M.D., Danuta Perek, M.D., Brandie Metz, M.D., Sebastien Barbarot, M.D., Annabel Maruani, M.D., Ph.D., Zsuzsanna Zsofia Szalai, M.D., Ph.D., Alfons Krol, M.D., Olivia Boccara, M.D., Regina Foelster-Holst, M.D., Maria Isabel Bosch, M.D., John Su, M.D., Hana Buckova, M.D., Ph.D., Antonio Torrelo, M.D., Frederic Cambazard, M.D., Rainer Grantzow, M.D., Orli Wargon, M.D., Dariusz Wyrzykowski, M.D., Jochen Roessler, M.D., Jose Bernabeu-Wittel, M.D., Adriana M. Valencia, M.D., Przemyslaw Przewratil, M.D., Sharon Glick, M.D., Elena Pope, M.D., Nicholas Birchall, M.D., Latanya Benjamin, M.D., Anthony J. Mancini, M.D., Pierre Vabres, M.D., Pierre Souteyrand, M.D., Ilona J. Frieden, M.D., Charles I. Berul, M.D., Cyrus R. Mehta, Ph.D., Sorilla Prey, M.D., Franck Boralevi, M.D., Caroline C. Morgan, D.Phil., Stephane Heritier, Ph.D., Alain Delarue, M.D., and Jean-Jacques Voisard, M.D.
The authors' affiliations are listed in the Appendix. Address reprint requests to Dr. Léauté-Labrèze at Unité de Dermatologie Pédiatrique, Hôpital Pellegrin-Enfants, Pl. Amélie Raba Léon, 33 076 Bordeaux CEDEX, France, or at christine.labreze@chu-bordeaux.fr.

 

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