Background and Aims

Remimazolam is an ultrashort-acting benzodiazepine.

Methods

We performed a randomized double-blind comparison of remimazolam to placebo for outpatient colonoscopy. This study design was a requirement of the U.S. Food and Drug Administration. An additional group was randomized to open-label midazolam administered according to its package insert instructions (the randomization ratio for remimazolam:placebo:midazolam was 30:6:10). Study medications were administered under the supervision of the endoscopist, without any involvement of an anesthesia specialist. Patients were given 50 to 75 μg of fentanyl before receiving study medications. Patients who failed to achieve adequate sedation in any arm were rescued with midazolam dosed at the investigator’s discretion. The primary endpoint was a composite that required 3 criteria be met: completion of the colonoscopy, no need for rescue medication, and ≤5 doses of remimazolam or placebo in any 15-minute interval (≤3 doses of midazolam in any 12-minute interval in the open-label midazolam arm).

Results

There were 461 randomized patients in 12 U.S. sites. The primary endpoint was met for remimazolam, placebo, and midazolam in 91.3%, 1.7%, and 25.2% of patients, respectively (P < .0001 for remimazolam vs placebo). Patients administered remimazolam received less fentanyl, had faster recovery of neuropsychiatric function, were ready for discharge earlier, and felt back to normal sooner than patients with both placebo and midazolam. Hypotension was less frequent with remimazolam, and hypoxia occurred in 1% of patients with remimazolam or midazolam. There were no treatment-emergent serious adverse events.

Conclusion

Remimazolam can be administered safely under the supervision of endoscopists for outpatient colonoscopy, and it allows faster recovery of neuropsychiatric function compared with placebo (midazolam rescue) and midazolam. (Clinical trial registration number: NCT02290873.)

中文翻译：

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一项III期研究评估了雷马咪唑仑（CNS 7056）与安慰剂和咪达唑仑在结肠镜检查患者中的疗效和安全性

背景和目标

Remimazolam是一种超短效苯并二氮杂。

方法

我们对门诊结肠镜检查进行了雷马唑仑与安慰剂的随机双盲比较。该研究设计是美国食品和药物管理局的要求。根据其包装说明书将另一组随机分配给开放标记的咪达唑仑（remimazolam：安慰剂：midazolam的随机比例为30：6：10）。研究药物在内镜医师的监督下给药，而没有麻醉专家的参与。在接受研究药物之前，给患者服用50至75μg的芬太尼。在研究人员的酌情决定下，使用咪达唑仑营救了任何一只手臂均未达到充分镇静作用的患者。主要终点是需要满足3个标准的复合材料：完成结肠镜检查，无需急救药物，

结果

在美国的12个地点有461名随机分组的患者。remimazolam，安慰剂和咪达唑仑的主要终点指标分别达到91.3％，1.7％和25.2％（ remimazolam vs安慰剂的P <.0001）。与使用安慰剂和咪达唑仑的患者相比，使用雷马唑仑的患者接受的芬太尼较少，神经精神功能的恢复更快，可以早日出院，并且可以更快地恢复正常。remimazolam的低血压发生率较低，remimazolam或midazolam的患者中有1％发生低氧。没有出现紧急治疗的严重不良事件。

结论

Remimazolam可以在内镜医师的监督下安全地进行门诊结肠镜检查，与安慰剂（咪达唑仑抢救）和咪达唑仑相比，可以更快地恢复神经精神功能。（临床试验注册号：NCT02290873。）