Randomised controlled trial for emphysema with a selective agonist of the &ggr;-type retinoic acid receptor
Randomised controlled trial for emphysema with a selective agonist of the &ggr;-type retinoic acid receptor
复制标题
使用选择性激动剂治疗肺气肿的随机对照试验
DOI：
10.1183/09031936.00161911
复制
发表时间：
2012
影响因子：
24.3
通讯作者：
A. Rames
中科院分区：
文献类型：
--
作者：
J. Stolk;R. Stockley;B. Stoel;B. Cooper;E. Piitulainen;N. Seersholm;K. Chapman;J. Burdon;M. Decramer;R. Abboud;G. Mannes;E. Wouters;J. Garrett;J. C. Barros;E. Russi;D. Lomas;W. Macnee;A. Rames
帕罗伐汀是一种口服选择性类维生素A激动剂。在动物肺气肿模型中，帕罗伐汀减少炎症，促进结构修复和功能改善。REPAIR（维甲酸治疗1-抗胰蛋白酶国际注册研究中的肺气肿患者）是一项治疗发起的、双盲、安慰剂对照的随机研究，旨在评估262例经计算机断层扫描证实的重度1-抗胰蛋白酶缺乏症和肺气肿患者接受帕罗伐汀5 mg·d-1治疗1年的安全性和有效性。1年内容量调整的第15百分位数点肺密度相对于基线的变化是主要终点;还定期评估功能终点。我们将133名和129名患者分别随机分配到安慰剂组和帕罗伐汀组。两组的所有基线特征（包括呼吸系统药物）均匹配良好。88%和85%的患者分别完成了安慰剂和帕罗伐汀治疗1年。帕罗伐汀通常耐受良好。在研究完成者人群中，第28周时肺密度的安慰剂校正差异为-0.45 HU（p=0.64），第52周时为-0.25 HU（p=0.94）。随着时间的推移，观察到肺的大多数功能参数无显著性治疗差异，有利于药物，表明帕罗伐汀的潜在药理学作用。帕罗伐汀5 mg·d −1持续1年未能对继发于重度1-抗胰蛋白酶缺乏的中重度肺气肿患者的肺密度显示出显著的益处。
Palovarotene is an oral &ggr;-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement. REPAIR (Retinoid treatment of Emphysema in Patients on the &agr;1-antitrypsin International Registry), was an investigator-initiated, double-blind, placebo-controlled randomised study to assess the safety and efficacy of 5 mg·day−1 palovarotene given for 1 year to 262 patients with severe &agr;1-antitrypsin deficiency and emphysema confirmed by computed tomography. Change in volume-adjusted 15th percentile point lung density from baseline in 1 year was the primary end-point; functional end-points were also regularly assessed. We randomly assigned 133 and 129 patients to placebo or palovarotene, respectively. Both groups were well matched for all baseline characteristics, including respiratory medications. 88% and 85% of patients completed 1 year of treatment with placebo and palovarotene, respectively. Palovarotene was generally well tolerated. In the study completers population, the placebo-corrected difference of lung density was -0.45 HU at week 28 (p=0.64) and -0.25 HU at week 52 (p=0.94). A nonsignificant treatment difference in most functional parameters of the lung in favour of the drug was observed over time suggesting potential pharmacological effects of palovarotene. Palovarotene 5 mg·day−1 over 1 yr failed to show a significant benefit on lung density in moderate-to-severe emphysema secondary to severe &agr;1-antitrypsin deficiency.
影响因子：
9.6
作者：
Roth, Michael D.;Connett, John E.;Wise, Robert A.
通讯作者：
Wise, Robert A.