METHODS: In a multicentre randomised crossover trial, 19 patients with moderate-to-severe OSA received AtoOxy (80/5 mg), acetazolamide (500 mg), combined AtoOxy-plus-acetazolamide or placebo at bedtime for three nights (half doses on first night) with a 4-day washout between conditions. Outcomes were assessed at baseline and night 3 of each treatment period. Mixed model analysis compared the reduction in Apnoea-Hypopnoea Index (AHI) from baseline between AtoOxy-plus-acetazolamide and AtoOxy (primary outcome). Secondary outcomes included hypoxic burden and arousal index.
RESULTS: Although AtoOxy lowered AHI by 49 (33, 62)%baseline (estimate (95% CI)) vs placebo, and acetazolamide lowered AHI by+34 (14, 50)%baseline vs placebo, AtoOxy-plus-acetazolamide was not superior to AtoOxy alone (difference: -2 (-18, 11)%baseline, primary outcome p=0.8). Likewise, the hypoxic burden was lowered with AtoOxy (+58 (37, 71)%baseline) and acetazolamide (+37 (5, 58)%baseline), but no added benefit versus AtoOxy occurred when combined (difference: -13 (-5, 39)%baseline). Arousal index was also modestly reduced with each intervention (11%baseline-16%baseline). Mechanistic analyses revealed that similar traits (ie, higher baseline compensation, lower loop gain) were associated with both AtoOxy and acetazolamide efficacy.
CONCLUSIONS: While AtoOxy halved AHI, and acetazolamide lowered AHI by a third, the combination of these leading experimental interventions provided no greater efficacy than AtoOxy alone. Failure of acetazolamide to further increase efficacy suggests overlapping physiological mechanisms.
BACKGROUND: NCT03892772.
方法:在一项多中心随机交叉试验中,19例中度至重度OSA患者接受了AtoOxy(80/5mg),乙酰唑胺(500毫克),联合AtoOxy-plus-acetazolazamide或安慰剂在睡前三个晚上(第一个晚上的一半剂量),并在条件之间进行4天的冲洗。在基线和每个治疗期的第3晚评估结果。混合模型分析比较了AtoOxy加乙酰唑胺和AtoOxy之间的呼吸暂停-呼吸不足指数(AHI)从基线的降低(主要结果)。次要结果包括缺氧负荷和唤醒指数。
结果:尽管与安慰剂相比,AtoOxy将AHI降低了49(33,62)%的基线(估计值(95%CI)),与安慰剂相比,乙酰唑胺使AHI基线降低+34(14,50)%,AtoOxy加乙酰唑胺并不优于单独的AtoOxy(差异:-2(-18,11)%基线,主要结果p=0.8)。同样,用AtoOxy(+58(37,71)%基线)和乙酰唑胺(+37(5,58)%基线)降低低氧负荷,但与AtoOxy相比,合并时没有增加益处(差异:-13(-5,39)%基线)。每次干预时,唤醒指数也略有降低(基线11%-基线16%)。机理分析显示,相似的特征(即,较高的基线补偿,较低的环增益)与AtoOxy和乙酰唑胺疗效相关。
结论:虽然AtoOxy将AHI减半,乙酰唑胺将AHI降低了三分之一,这些主要的实验干预措施的组合没有比单独的AtoOxy提供更大的疗效。乙酰唑胺不能进一步增加功效提示重叠的生理机制。
背景:NCT03892772。