The Role of Benzodiazepines in Breathlessness: A Single Site, Open Label Pilot of Sustained Release Morphine Together with Clonazepam
The Role of Benzodiazepines in Breathlessness: A Single Site, Open Label Pilot of Sustained Release Morphine Together with Clonazepam
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DOI：
10.1089/jpm.2012.0505
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发表时间：
2013-07-01
影响因子：
2.8
通讯作者：
Currow, David C.
中科院分区：
文献类型：
--
作者：
Allcroft, Peter;Margitanovic, Vera;Currow, David C.
背景：尽管对根本原因进行了最佳治疗，但在休息或最小运动时呼吸困难是令人痛苦和普遍的。阿片类药物可以减轻慢性顽固性呼吸困难的强度，抗焦虑药可能有益。该试点旨在确定通过在低剂量阿片类药物中添加常规苯二氮卓类药物来进行关于呼吸困难强度的III期研究的安全性和可行性。方法：这是一个单一的网站，在Kapanol（R）10 mg中添加常规氯硝西泮0.5 mg口服给药的开放标签II期研究（缓释硫酸吗啡）口服马内与多库酯/番泻苷在修改的医学研究理事会量表>= 2的人。第4天的呼吸困难强度是疗效结局。结果：11人接受了试验药物治疗（8名男性，中位年龄78岁（68至89岁）;所有人都患有COPD;中位数Karnofsky 70（50至80）; 6人长期在家吸氧。十人完成了第四天。一个人在第四天因为不稳定而退出。五名参与者达到了15%的减少，但只有三个继续扩展研究，所有完成无toxicity.Conclusion：这项研究是安全的，可行的，似乎有一组谁获得的好处滴定阿片类药物。鉴于苯二氮卓类药物广泛用于慢性难治性呼吸困难的对症治疗，且证据基础较差，因此有理由进行明确的III期研究。
Background: Breathlessness at rest or on minimal exertion despite optimal treatment of underlying cause(s) is distressing and prevalent. Opioids can reduce the intensity of chronic refractory breathlessness and an anxiolytic may be of benefit. This pilot aimed to determine the safety and feasibility of conducting a phase III study on the intensity of breathlessness by adding regular benzodiazepine to low-dose opioid.Methods: This is a single site, open label phase II study of the addition of regular clonazepam 0.5 mg nocte orally to Kapanol(R) 10 mg (sustained release morphine sulphate) orally mane together with docusate/sennosides in people with modified Medical Research Council Scale >= 2. Breathlessness intensity on day four was the efficacy outcome. Participants could extend for another 10 days if they achieved >15% reduction over their own baseline breathlessness intensity.Results: Eleven people had trial medication (eight males, median age 78 years (68 to 89); all had COPD; median Karnofsky 70 (50 to 80); six were on long-term home oxygen. Ten people completed day four. One person withdrew because of unsteadiness on day four. Five participants reached the 15% reduction, but only three went on to the extension study, all completing without toxicity.Conclusion: This study was safe, feasible and there appears to be a group who derive benefits comparable to titrated opioids. Given the widespread use of benzodiazepines for the symptomatic treatment of chronic refractory breathlessness and its poor evidence base, there is justification for a definitive phase III study.