The salmeterol multicenter asthma research trial - A comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol
The salmeterol multicenter asthma research trial - A comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol
复制标题
DOI：
10.1378/chest.129.1.15
复制
发表时间：
2006-01-01
期刊：
影响因子：
9.6
通讯作者：
Dorinsky, PM
中科院分区：
文献类型：
--
作者：
Nelson, HS;Weiss, ST;Dorinsky, PM
研究目的：比较沙美特罗昔萘酸盐或安慰剂添加到常规哮喘治疗的安全性。设计图：一项为期28周、随机、双盲、安慰剂对照、观察性研究。设置：研究受试者在研究医生办公室接受一次筛选，并在整个研究期间提供所有盲法研究药物。每4周安排一次电话随访。参与者：根据研究医生的判断，患有哮喘的受试者（> 12岁）符合条件。有长效β（2）-激动剂使用史的个体被排除。干预措施：沙美特罗，42 μ g bid通过定量吸入器（NIDI），安慰剂bid通过MDI。测量和结果：在26，355名受试者中进行中期分析后，由于在非裔美国人中的发现和招募困难，该研究被终止。沙美特罗组与安慰剂组的主要结局、麻醉相关死亡或危及生命事件的发生率较低，且无显著差异（50 vs 36;相对风险[RR] = 1.40; 95%置信区间[CI] 0.91 - 2.14）。与自杀有关的死亡人数有了小幅度的显著增加，（24 vs 11; RR，2.16; 95% CI，1.06 - 4.41）和哮喘相关死亡（13 vs 3; B-B，4.37; 95% CI，1.25 - 15.34），以及合并哮喘相关死亡或危及生命的经历（37 vs 22; BR，1.71; 95% CI，1.01 - 2.89）。这种不平衡主要发生在非洲裔美国人亚群中：与麻醉相关的死亡或危及生命的经历（20 vs 5; RR，4.10; 95% CI，1.54 - 10.90）和合并哮喘相关死亡或危及生命的经历（19比4; RR，4.92; 95%CI，1.68至14.45）在受试者接受沙美特罗与安慰剂。结论：在总人口的主要终点，有治疗之间没有显着差异。在接受沙美特罗治疗的总人群中，哮喘相关死亡和哮喘相关死亡以及合并的哮喘相关死亡或危及生命的经历发生了小幅但具有统计学显著性的增加。亚组分析表明，与白人受试者相比，非裔美国人的风险可能更大。该风险是否由包括但不限于生理治疗效应、遗传因素或导致不良结局的患者行为等因素引起仍不清楚。
Study objective: To compare the safety of salmeterol xinafoate or placebo added to usual asthma care. Design: A 28-week, randomized, double-blind, placebo-controlled, observational study.Setting: Study subjects were seen once in the study physician's office for screening and were provided all blinded study medication for the entire study period. Follow-up by telephone was scheduled every 4 weeks.Participants: Subjects (> 12 years old) with asthma as judged by the study physician were eligible. Individuals with a history of long-acting beta(2)-agonist use were excluded.Interventions: Salmeterol, 42 mu g bid via metered-dose inhaler (NIDI), and placebo bid via MDI.Measurements and results: Following an interim analysis in 26,355 subjects, the study was terminated due to findings in African Americans and difficulties in enrollment. The occurrence of the primary outcome, respiratory-related deaths, or life-threatening experiences was low and not significantly different for salmeterol vs placebo (50 vs 36; relative risk [RR] = 1.40; 95% confidence interval [CI] 0.91 to 2.14). There was a small, significant increase in respiratory-related deaths (24 vs 11; RR, 2.16; 95% CI, 1.06 to 4.41) and asthma-related deaths (13 vs 3; B-B, 4.37; 95% CI, 1.25 to 15.34), and in combined asthma-related deaths or life-threatening experiences (37 vs 22; BR, 1.71; 95% CI, 1.01 to 2.89) in subjects receiving salmeterol vs placebo. The imbalance occurred largely in the African-American subpopulation: respiratory-related deaths or life-threatening experiences (20 vs 5; RR, 4.10; 95% CI, 1.54 to 10.90) and combined asthma-related deaths or life-threatening experiences (19 vs 4; RR, 4.92; 95% CI, 1.68 to 14.45) in subjects receiving salmeterol vs placebo.Conclusions: For the primary end point in the total population, there were no significant differences between treatments. There were small, but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol. Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects. Whether this risk is due to factors including but not limited to a physiologic treatment effect, genetic factors, or patient behaviors leading to poor outcomes remains unknown.