大承气汤治疗原发性和非原发性急性肠梗阻合理剂量的随机对照、双盲、多中心临床研究

Rational Dose of Dachengqi Decoction (大承气汤) in the Treatment of Primary and Non-primary Acute Intestinal Obstruction:A Randomize-controlled,Double-Blinded,Multicentered Clinical Trial

目的 通过开展随机、双盲、剂量平行对照、多中心临床研究,明确大承气汤治疗急性肠梗阻的合理剂量,为临床合理选择大承气汤剂量提供证据支持。方法 基于大承气汤的临床基础常用剂量,设置低剂量(大黄12 g、厚朴9 g、枳实9 g、芒硝4.5 g)、中剂量(大黄36 g、厚朴27 g、枳实27 g、芒硝13.5 g)、高剂量(大黄60 g、厚朴45 g、枳实45 g、芒硝22.5 g) 3个组。将149例急性肠梗阻阳明腑实证患者按照分层区组随机方法以1∶1∶1的比例分配到3个组中,对患者和医生均设盲。各组均在西医常规治疗基础上,将每剂大承气汤生药提取制作成12袋颗粒剂,每6 h口服或通过胃导管注射1次,每次3袋,连续3天。治疗后分别统计原发性急性肠梗阻和非原发性急性肠梗阻患者各自3组的观察指标,并采用全分析集(FAS)和符合方案集(PPS)进行分析。主要疗效指标为治疗后恢复自主排便及自主排气时间;次要疗效指标为自主排便理想率、自主排气理想率;记录研究过程中不良事件的发生情况,采用安全分析集(SS)分析。结果 共有91例原发性急性肠梗阻患者和58例非原发性急性肠梗阻患者进入FAS和SS分析,80例原发性肠梗阻患者和56例非原发性肠梗阻进入PPS分析。FAS和PPS分析均显示,原发性急性肠梗阻患者不同剂量组别恢复自主排便及自主排气时间比较,差异均具有统计学意义(P<0.01),其中高剂量组、中剂量组均低于低剂量组(P<0.05);3组自主排便理想率、自主排气理想率比较差异无统计学意义(P>0.05)。非原发性急性肠梗阻患者的FAS和PPS分析结果与原发性急性肠梗阻结果一致。原发性急性肠梗阻患者发生5例不良事件(低剂量组3例,中剂量组1例,高剂量组1例,主要表现为腹胀、腹痛),不良事件发生率比较差异无统计学意义(P>0.05)。非原发性急性肠梗阻患者未发生不良事件。结论 临床可用大承气汤中剂量作为原发性急性肠梗阻患者的较优剂量,高剂量作为非原发性急性肠梗阻患者的较优剂量,疗效优势主要体现在以更短的时间恢复自主排便和自主排气,改善肠道功能。

Objective To determine the optimal dose of Dachengqi Decoction(大承气汤,DCQD)for the treatment of acute intestinal obstruction(AIO)through a randomized,double-blind,dosage parallel controlled,multi-center clinical trial,and to providee evidence support for the reasonable dosage of DCQD in clinical practice.Methods Based on the commonly used clinical dose of DCQD,three different groups were set up,including low-dose group which used Dahuang(Radix et Rhizoma Rhei)12 g,Houpo(Cortex Magnoliae Officinalis)9 g,Zhishi(Fructus Aurantii Immaturus)9 g,and Mangxiao(Natrii Sulfas)4.5 g,medium-dose group using Dahuang 36 g,Houpo 27 g,Zhishi 27 g,Mangxiao 13.5 g,and high-dose group using Dahuang 60 g,Houp045 g,Zhishi 45 g and Mangxiao 22.5 g.Initially,149 AIO patients with Yangming(阳明)bowel excess syndrome were randomly assigned to three groups using a stratified randomization method,and both the patients and the doctors were blinded.In addition to conventional western medicine treatment,each group was given 12 bags of granules made from the raw herbs of DCQD at different doses,taken orally or injected through a gastric catheter once every 6 hours,3 bags each time,for 3 consecutive days.After treatment,the indicators of the three groups of patients with primary AIO and non-primary AIO were evaluated respectively,and the full analysis set(FAS)and per-protocol set(PPS)were used for analysis.The primary outcomes were the time to recover voluntary bowel movements and voluntary flatulence.The secondary outcomes were the ideal rate of spontaneous defecation and the ideal rate of spontaneous flatus.The occurrence of adverse events during the study was recorded and analyzed using the safety analysis set(SS).Results A total of 91 patients with primary AIO and 58 patients with non-primary AIO were included in the FAS and SS analysis,while 80 primary AIO patients and 56 non-primary AIO patients were included in the PPS analysis.Both FAS and PPS analysis showed significant differences in the time to recover voluntary bowel movements and voluntary flatulence among primary AIO patients in different dose groups of DCQD(P<0.01),and the high-and medium-dose groups assumed less time than the low-dose group(P<0.05).There was no statistically significant difference in the ideal rate of spontaneous defecation and spontaneous flatus among the three groups(P>0.05).And consistent results were seen in the non-primary AIO patients among the three groups.Five adverse events occurred in primary AIO patients(3 in the low-dose group,1 in the medium-dose group,and 1 in the high-dose group),mainly manifested as abdominal distension and abdominal pain,and there was no statistically significant difference in the incidence of adverse events(P>0.05).No adverse events occurred in patients with non-primary AIO.Conclusion DCQD,as an effective treatment for patients with AIO,is commonly used at a medium dose for patients with primary AIO and at a high dose for patients with non-primary AIO.The therapeutic advantage is mainly reflected in the shorter time to recover spontaneous defecation and spontaneous flatulence and the improvement of intestinal function.