Alam N H, Ashraf H, Khan W A, Karim M M, Fuchs G J
Clinical Sciences Division, International Centre for Diarrhoeal Disease Research (ICDDR,B): Centre for Health and Population Research, Dhaka, Bangladesh.
Gut. 2003 Oct;52(10):1419-23. doi: 10.1136/gut.52.10.1419.
The enkephalins, endogenous opiate substances, act as neurotransmitters along the entire digestive tract where they elicit intestinal antisecretory activity without affecting intestinal transit time or motility. Racecadotril, through inhibition of enkephalinase, reinforces the physiological activity of endogenous enkephalins and, therefore, shows intestinal antisecretory activity.
We conducted the study to determine the role of racecadotril as an adjunct to the standard treatment of cholera in adults.
The study was a double blind, randomised, placebo controlled clinical trial involving 110 adult male cholera patients who received either racecadotril or placebo in addition to standard cholera treatment. The major outcome measures (stool output, oral rehydration solution (ORS) intake, requirements for unscheduled intravenous fluid infusion, and duration of diarrhoea) were compared between the groups.
Of 110 patients enrolled, 54 received racecadotril and 56 received placebo. Admission clinical characteristics were comparable between the groups. There was no significant difference in (mean (SD)) total stool output (racecadotril v placebo 315 (228) v 280 (156) g/kg), total ORS intake (390 (264) v 369 (240) ml/kg), or duration of diarrhoea (35 (15) v 32 (13) hours) between the groups. Clinical success, defined as resolution of diarrhoea within 72 hours of initiation of study intervention, was similar in both groups (racecadotril v placebo 96% v 89%). The number of patients receiving unscheduled intravenous infusions was not significantly different between the groups (racecadotril v placebo 22% v 14%). No drug related adverse effect was noted.
The study demonstrated that racecadotril therapy, although found to be safe, does not provide additional benefit in the treatment of severe cholera in adults.
脑啡肽作为内源性阿片类物质，在整个消化道中充当神经递质，可引发肠道抗分泌活性，而不影响肠道转运时间或蠕动。消旋卡多曲通过抑制脑啡肽酶，增强内源性脑啡肽的生理活性，因此具有肠道抗分泌活性。
我们开展本研究以确定消旋卡多曲作为成人霍乱标准治疗辅助药物的作用。
本研究为双盲、随机、安慰剂对照临床试验，纳入110例成年男性霍乱患者，除接受标准霍乱治疗外，分别给予消旋卡多曲或安慰剂。比较两组的主要结局指标（粪便排出量、口服补液盐（ORS）摄入量、非计划静脉输液需求量及腹泻持续时间）。
110例入组患者中，54例接受消旋卡多曲治疗，56例接受安慰剂治疗。两组入院时的临床特征具有可比性。两组间（均值（标准差））总粪便排出量（消旋卡多曲组vs安慰剂组：315（228）g/kg vs 280（156）g/kg）、总ORS摄入量（390（264）ml/kg vs 369（240）ml/kg）或腹泻持续时间（35（15）小时vs 32（13）小时）无显著差异。临床治愈定义为研究干预开始后72小时内腹泻症状缓解，两组相似（消旋卡多曲组vs安慰剂组：96% vs 89%）。两组间接受非计划静脉输液的患者数量无显著差异（消旋卡多曲组vs安慰剂组：22% vs 14%）。未观察到与药物相关的不良反应。
本研究表明，消旋卡多曲治疗虽安全，但对成人重症霍乱治疗无额外益处。
