■需要假对照试验来表征舌下神经刺激(HGNS)治疗对中度-重度阻塞性睡眠呼吸暂停(OSA)患者心血管终点的影响。
■为了确定HGNS治疗水平的影响,与假水平相比,关于血压,交感神经活动,和血管功能。
■这种双盲,假控制,随机交叉治疗试验于2018年至2022年在3个独立的学术医疗中心进行.包括已经植入HGNS装置并且粘附和临床上优化HGNS治疗的患有OSA的成年患者。在HGNS植入前1年内开车时睡着的参与者被排除在试验之外。数据分析于2022年1月至9月进行。
参与者按照随机顺序接受4周的积极HGNS治疗和4周的假HGNS治疗。每4周收集24小时动态血压监测(ABPM),射血前期(PEP),和流动介导的扩张(FMD)值。
■平均24小时收缩压的变化是主要结果,与其他ABPM终点探索,PEP和FMD是次要终点。
■参与者(n=60)年龄较大(平均[SD]年龄,67.3[9.9]年),超重(平均[SD]体重指数,以公斤为单位的重量除以以米为单位的高度的平方计算,28.7[4.6]),以男性为主(38[63%]),基线时患有严重OSA(平均[SD]呼吸暂停低通气指数,33.1[14.9]个事件/小时)。在24小时收缩压的积极治疗和假治疗之间没有观察到差异(积极治疗的平均变化,-0.18[95%CI,-2.21至1.84]mmHg),PEP(积极治疗的平均变化,0.11[95%CI,-5.43至5.66]毫秒),或口蹄疫(积极治疗的平均变化,-0.17%[95%CI,-1.88%至1.54%])。在符合方案的分析集(n=20)中观察到主动和假治疗之间的较大差异,所述分析集被定义为在假治疗和主动治疗之间呼吸暂停-低通气指数降低至少50%。
■在这项假对照HGNS随机临床试验中,假治疗和主动HGNS治疗的平均24小时收缩压和其他心血管指标无显著差异.可以收集一些方法学课程,为未来的HGNS随机临床试验提供信息。
■ClinicalTrials.gov标识符:NCT03359096。
Sham-controlled trials are needed to characterize the effect of hypoglossal nerve stimulation (HGNS) therapy on cardiovascular end points in patients with moderate-severe obstructive sleep apnea (OSA).
To determine the effect of therapeutic levels of HGNS, compared to sham levels, on blood pressure, sympathetic activity, and vascular function.
This double-blind, sham-controlled, randomized crossover therapy
trial was conducted from 2018 to 2022 at 3 separate academic medical centers. Adult patients with OSA who already had an HGNS device implanted and were adherent and clinically optimized to HGNS therapy were included. Participants who had fallen asleep while driving within 1 year prior to HGNS implantation were excluded from the
trial. Data analysis was performed from January to September 2022.
Participants underwent a 4-week period of active HGNS therapy and a 4-week period of sham HGNS therapy in a randomized order. Each 4-week period concluded with collection of 24-hour ambulatory blood pressure monitoring (ABPM), pre-ejection period (PEP), and flow-mediated dilation (FMD) values.
The change in mean 24-hour systolic blood pressure was the primary outcome, with other ABPM end points exploratory, and PEP and FMD were cosecondary end points.
Participants (n = 60) were older (mean [SD] age, 67.3 [9.9] years), overweight (mean [SD] body mass index, calculated as weight in kilograms divided by height in meters squared, 28.7 [4.6]), predominantly male (38 [63%]), and had severe OSA at baseline (mean [SD] apnea-hypopnea index, 33.1 [14.9] events/h). There were no differences observed between active and sham therapy in 24-hour systolic blood pressure (mean change on active therapy, -0.18 [95% CI, -2.21 to 1.84] mm Hg), PEP (mean change on active therapy, 0.11 [95% CI, -5.43 to 5.66] milliseconds), or FMD (mean change on active therapy, -0.17% [95% CI, -1.88% to 1.54%]). Larger differences between active and sham therapy were observed in a per-protocol analysis set (n = 20) defined as experiencing at least a 50% reduction in apnea-hypopnea index between sham and active treatment.
In this sham-controlled HGNS randomized clinical
trial, mean 24-hour systolic blood pressure and other cardiovascular measures were not significantly different between sham and active HGNS therapy. Several methodologic lessons can be gleaned to inform future HGNS randomized clinical trials.
ClinicalTrials.gov Identifier: NCT03359096.